THE REPRODUCTIVE SYSTEM; PREGNANCY AND HUMAN DEVELOPMENT

Anatomy of the Male Reproductive System:

The Testis

a) A pair of organs each surrounded by two tunics-the outer tunica vaginalis which is derived from peritoneum and the innermost tunica albuginea which is the white fibrous capsule of the testis.

b) The testis are divided by septa extending from the tunica albuginea into 250-300 wedge-shaped lobules each containing seminiferous  tubules. The seminiferous tubules of each lobule converge to form a tubulus rectus which is a tube which conducts the sperm into the rete testis (a tubular network on the posterior side of the testis) from which sperm leave the testis through the efferent ductules and enter the epididymis .

c) Interstitial cells or Leydig cells are found within the connective tissue surrounding the seminiferous tubules which produce male sex hormones called androgens, the most important of which is testosterone. Note that the sperm producing functions are carried out in the seminiferous tubules (sperm factories), and the hormone producing functions by the interstitial cells.

d) The blood vessels that supply the testis consist of the testicular arteries which branch from the abdominal aorta, and the testicular veins which arise from the vinelike network called the pampiniform plexus.  The pampiniform plexus absorbs heat from the arterial blood, cooling it before it enters the testis.

e) The testis are under both sympathetic and parasympathetic control. The nerve fibers are enclosed along with blood vessels and lymphatics  in  a connective tissue sheath called the spermatic cord.

The Scrotum

a) The paired testis lie suspended outside of the body cavity (abdominopelvic cavity) within a sac of skin called the scrotum. The scrotum is divided into right and left halves by a midline septum providing one compartment for each testis.

b) The reason that the testis are outside of our body cavity is because sperm cannot be produced at our body temperature of 98.6 degrees F (36.2 degrees C).  By suspending the testis outside of our body within the scrotum, a temperature is provided about 3 degrees C lower which is the proper temperature for sperm production (33.2 degrees C). Males will become temporarily sterile at times such as during a high body fever, and also when taking a hot bath.

c) The scrotum is also a temperature regulating device for sperm production. When it is cold, the scrotum contracts pulling the testis closer to the warmth of our body while decreasing the surface area of the scrotum for minimal loss of heat , and the scrotum relaxes and lowers the testis away from the body and the surface area of the scrotum is larger to increase the surface area for optimal cooling. 

d) Two sets of muscles function in  raising and lowering the testis by the scrotum: the dartos muscle which is a layer smooth muscle in the superficial fascia contracts and wrinkles the scrotal skin, and the cremaster muscles which are bands of skeletal muscle that arise from the internal oblique muscles of the trunk which act to elevate the testes.

The Penis

a) This is an organ used for copulation (a delivering of the sperm into the female reproductive organ.

b) The penis along with the scrotum hang suspended from the perineum make up the external genitalia of the male.

c) A diamond shaped region located between the pubic symphysis anteriorly, and the coccyx posteriorly, and the ischial tuberosities laterally is the male perineum (meaning around the anus). Muscles are found within the perinium discussed in chapter 10 which control urination, defecation, and the erection of the penis. 

d) The penis consists of two parts: the root of the penis, and the shaft of the penis which ends in an enlarged tip called the glans penis.

e) The shaft of the penis is that part of the penis which extends from the body and is covered by a loose layer of skin which slides distally to form a cuff of skin called the prepuce or foreskin surrounding the glans penis.  The  prepuce is normally absent on human males after birth in that it is surgically removed by a surgeon by a process called circumcision, for health reasons.

f) Internally the penis contains the urethra (through which both urine and semen can be transported) surrounded by three long cylindrical bodies of erectile tissue.   The erectile tissue consists of a spongy network of connective tissue and smooth muscle containing many vascular spaces which becomes filled with blood resulting in an event called erection which occurs during sexual excitement.                                                                        

g) The midventral body of erectile tissue is called the corpus spongiosum which directly surrounds the urethra. The corpus spongiosum also expands distally to form the glans penis and proximally  to form the part of the root called the bulb of the penis. The muscle responsible for maintaining an erection is the bulbospongiosus muscle  and attaches to the bulb of the penis.

h) There is  a pair of dorsal erectile bodies called the corpora cavernosa which make up most of the penis and are bound by the fibrous tunica albuginea. Proximally their ends form the crura  (legs) of the penis. Each crus is surrounded by an ischiocavernosus muscle and anchors to the pubic arch of the bony pelvis.

The Male Duct System

a) Transport of sperm travel from the testis to the outside of the body through a system of accessory ducts in the following order (proximal to distal): the epididymis, the ductus deferens, and the urethra. 

b) The epididymis is about 3.8 cm long and is comma shaped.  The head (of the comma) of the epididymus joins the efferent ductules, and is located  superior to the testis. The body and tail (of the comma) of the epididymus are located posterior and laterally to each testis. The duct of the epidiymus consists of a coiled tube which if were uncoiled would be 20 feet long. Lining the duct is the duct mucosa which contain pseudostratified epithilium some of which contain contain microvilli (steriocilia) which absorb excess testicular fluid and pass nutrients to the sperm in the lumen.  It takes 20 days for the sperm to make a trip through the duct of the epididymus, they eventually mature and gain the ability to swim. Contraction of the smooth muscle within the duct during sexual excitement expels sperm from the tail of the epididymus into the next segment of the duct system called the ductus deferens.  Sperm can be stored in the epididymus for several months, if held longer they will be phagocytized by epithelial cells in the epididymus. Sperm production begins at the age of puberty and are constantly being made throughout the life of the male by the millions.

c) The ductus deferens or vas deferens (18 inches long) ascends as part of the spermatic cord from the epididymus  posteriorly through the inquinal canal and into the pelvic cavity passing anterior to the pubic bone, looping medially over the ureter and descends along the posterior wall of the bladder. It then expands to form the ampulla and then joins with the duct of the seminal vesicle (a gland)  to form a short ejaculatory duct. Each ejaculatory duct then passes into the prostrate gland where it empties into the urethra. At the moment of ejaculation, layers of smooth muscle present in the vas deferens produce peristaltic waves propelling the sperm forward.  A vasectomy can be performed as a method of birth control for men by having the vas deferens surgically cut as it passes through the scrotum.

d) The urethra is the final accessory duct in the male system conveying both urine and semen (at  different times). It is divided into  1) the prostatic urethra (the portion surrounded by the prostrate gland 2) the membraneous urethra  in the urogenital diaphragm and 3) the spongy (penile) urethra which runs through the penis and opens to the outside at the external urethral orifice. The spongy urethra is about 6 inches long.

Accessory Glands

a) The seminal vesicles release a secretion which accounts for 60% of the volume of semen.  This secretion is a yellow, viscous, alkaline fluid containing fructose sugar, ascorbic acid, a coagulating enzyme (vesiculase, and prostaglandins. Sperm mix  with this secretion as they pass the seminal vesicles from the vans deferens and both enter as a mixture into the prostatic urethra.

b) The prostate gland is a doughnut shaped gland about the size of a chestnut that encircles the prostatic urethra.   It is enclosed by a connective tissue capsule and is made up of 20 to 30 compound tubular-alveolar glands embedded in a mass (stroma) of smooth muscle and dense connective tissue. The prostatic gland secretion accounts for about 33% of the semen volume and is a milky, slightly acid fluid that contains citrate (a nutrient source) and several enzymes (fibrinolysin, hyaluronidase, and acid phosphatase), and prostate specific antigen (PSA) and plays a role in activating the sperm. This fluid combines with the sperm and the fluid from the seminal vesicles at the prostatic urethra.  A rise in PSA levels in the blood is a "tumor marker" and can be due to prostate cancer which is the third most prevalent cancer in men.   Digital exams detecting a swollen inflammation of the prostate (prostatitis) which results in painful urination from blocking the urethra is also a symptom of this disease.

c) The bulbourethral  glands, also called Cowper's glands are the final accessory glands found in the male reproductive system.  They are found inferior to the prostate gland and produce a thick clear mucus prior to ejaculation that drains into the spongy urethra and neutralizes traces of acidic urine in the urethra.

Semen

a) This is a mixture of sperm and accessory gland secretions mentioned above. It provides a transport medium for the sperm from the male to the female, as well as nutrients for the sperm (nearly all their fuel comes from the fructose from the seminal vesicles), and chemicals that protect and activate the sperm and facilitate their movement.  The prostaglandins decrease the viscosity of mucus guarding the entry (cervix) of the uterus, while stimulating reverse peristalsis in the uterus and medial parts of the uterine tubes which results in facilitating the movement of sperm through the female reproductive tract. 

b) There are certain enzymes in semen which will act with the hormone relaxin to enhance sperm motility. The pH of semen is slightly alkaline or basic (pH 7.2-7.6) and helps to neutralize the acid environment of the male's urethra and the female's vagina. Sperm are very sluggish under acid conditions  (below pH of 6). 

c) Semen also contains an antibiotic called seminalplasmin which destroys certain bacteria. The purpose of the fibrinogen which are clotting factors act to coagulate the semen just after ejaculation, and after copulation the fibrinolysin liquefies the semen enabling the sperm to swim faster as it reaches the female reproductive system.  Semen amounts are about 2-5 ml, containing about 50 and 130 million sperm. 

Hormonal Regulation of Testicular Function ( Figure 28.10)

Spermmatogenesis and Spermiogenesis (Figure 28.8 and Figure 28.9)

Anatomy of the Female Reproductive System

The Ovaries

a) Two ovaries (female gonads) are held in place by the ovarian ligament which anchors them medially to the uterus, the suspensory ligament anchoring them laterally to the pelvic wall, and the mesovarium anchors each ovary  in between.  The suspensory ligament and the mesovarium are part of the broad ligament (a peritoneal fold that forms a tent like structure over the uterus and supports the uterine tubes, uterus, and vagina.

b) Branches of the abdominal aorta serve the ovaries by way of the ovarian arteries and by the ovarian branch of the uterine arteries and can be found reaching the ovaries by traveling through the suspensory ligaments and mesovaria.

c) Each ovary is surrounded externally by the tunica albuginea, which in turn covered externally by a layer of cuboidal epithelial cells called the germinal epithelium which is continuous with the the peritoneum of the mesovarium.

d) The ovary has an outer cortex within which are found ovarian follicles each containing an immature egg called an oocyte.  Each oocyte is enclosed by one or more layers of different cells.   If a single layer of cells covers an oocyte they are called follicle cells, and granulosa cells if more than one layer is present.

e) Present within the outer cortex are follicles in different stages of development and are structurally different from one another: primordial follicles have only one layer of squamous like follicle cells surround the ova which will turn into  a primary follicle which has two or more layers of columnar-type granulosa cells enclosing the ova which in turn becomes a secondary follicle when fluid filled spaces appear between the granulosa cells and then coalesce to form  a central fluid-filled cavity (the antrum), and finally at the mature stage called a vesicular (Graafian) follicle, the follicle bulges from the surface of the ovary.

f) One of the ripening follicles will eject its oocyte from the ovary once a month in an adult female in a process called ovulation. After ovulation the ruptured follicle is transformed into the corpus luteum which eventually degenerates leaving the ovary scarred and pitted revealing the many oocytes that have been released during the life of the female.

The Female Duct System

The Uterine Tubes

a) Uterine tubes (fallopian tubes or oviducts) receive the oocyte in the distal open funnel shaped portion called the infundibulum that "drapes" over the ovary.  The uterine tubes have little or no actual contact with the ovaries. Oocytes are cast into the peritoneal cavity and many oocytes are lost there. The infundibulum "bends" over the ovary while tiny ciliated finger like projections called fimbriae stiffen and sweep the ovarian surface for oocytes.  The beating cilia on the fimbriae then create currents in the peritoneal fluid that act to carry the oocyte into the next part of the uterine tube called the ampullae. It will be within  the ampullae which has a slightly larger diameter than the rest  of the uterine tube that  fertilization of the egg (oocyte) will be take place  by sperm from the male.  The fertilized egg will travel through the 4 inch uterine tube through a constricted area of the uterine tube called the isthmus into the uterus.

b) The wall of the uterine tubes also contain sheets of smooth muscle whose contractions (peristalsis) help move the fertilized oocyte along. The mucosa lining the uterine tubes is highly folded and contains both ciliated and nonciliated cells  which also help move the oocyte along. The beating of the cilia by the ciliated cells, while the nonciliated cells which contain dense microvilli produce a secretion the keeps the oocyte moist and nourished.

c) Externally the uterine tubes are covered by visceral peritoneum and supported along their length by a short mesentery (part of the broad ligament) called the mesosalpinx.

The Uterus

a) The uterus (womb) functions in receiving retaining (implantation of the fertilized egg occurs here), and nourishing the fertilized ovum. It is a hollow organ about the size of an inverted  pear in  premenopausal women who have never been pregnant, but is somewhat larger in women who have borne children. The uterus is normally flexed anteriorly where it joins the vagina (anteverted), in younger women while in older women it is frequently turned backward (retroverted).

b) The major portion of the uterus is the body, while the region superior to the entrance of the uterine tubes is the fundus, and the slightly narrowed region between the body and the cervix is the isthmus.  The cervix of the uterus is its narrow neck which projects into the vagina and the cavity of the cervix is called the cervical canal which communicates with the vagina by way of an opening called the external os and with the uterine body by way of the internal os.  The mucosa of the cervical canal contains cervical glands that secrete a mucus that fills the cervical canal and covers the external os  to block the spread of bacteria from the vagina into the uterus. Cervical mucus also blocks the entry of sperm, except at midcycle when it becomes less viscous and allows sperm to pass through.

c) The uterus is supported by the mesometrium portion of the broad ligament laterally, inferiorly by the lateral cervical (cardinal) ligaments which extend from the cervix and superior part of the vagina to the lateral walls of the pelvis , and by the paired uterosacral ligaments which secure the uterus to the sacrum posteriorly. Fibrous round ligaments bind the anterior wall of the uterus which run through the inquinal canals  to anchor in the subcutaneous tissues of the labia majora (outer lips of the vulva).  The ligaments allow the uterus a good deal of mobility, and its position changes as the rectum and bladder fill and empty.

d) The vesicouterine pouch between the bladder and the uterus, and the rectouterine pouch between the rectum and the uterus are blind ended peritoneal pouches formed around the uterus by the peritoneum.

e) The uterine wall is composed of three layers. The perimetrium ,the outermost serous layer, is the visceral peritoneum.  The myometrium (muscle of the uterus) is the middle layer composed of bundles of smooth muscle.  The myometrium contracts rhythmically during childbirth to expel the baby from the mother's body.  The endometrium is the mucosal lining of the uterine cavity and is a simple columnar epithelium underlain by a thick lamina propria of highly cellular connective tissue. It is here that the young embryo will become implanted residing there for the rest of its development.

f) Two layers are found forming the endometrium. The stratum functionalis or functional layer undergoes cyclic changes in response to blood levels of ovarian hormones and is shed during menstruation. The thinner deeper layer is the stratum basalis or basal layer which forms a new functionalis after menstruation ends.  It is unresponsive to ovarian hormones.  The endometrium has numerous uterine glands that change in length as the endometrial thickness changes.

g) Blood supply to the uterus is accomplished by the uterine arteries arising from the internal iliacs ascending along the sides of the uterus sending branches into the uterine walls.   The branches break up into several arcuate arteries within the myometerium.  The arcuate arteries branch into radial arteries into the endometrium where they in turn give off straight arteries to the stratum basalis and spiral (coiled) arteries to the stratum functionalis.  The spiral arteries undergo repeated degeneration and regeneration, and it is their spasms that actually cause the functionalis layer to be shed during menstruation.  Veins in the endometrium are thin-walled and form an extensive network with occasional sinusoidal enlargements.

The Vagina

a) A thin tube shaped organ about 3-4 inches long provides a place for copulation by the male penis during sexual intercourse. Also called the birth canal, the vagina also provides the passageway for delivery of the infant and also for menstrual flow.  The urethra is embedded in its anterior wall and provides a separate passageway for the excretion of urine (unlike the male penis). 

b) The wall of the vagina consists of three coats: an outer fibroelastic adventitia, a smooth muscle muscularis, and a mucosa marked with transverse ridges or rugae.  The rugae act to stimulate the penis during intercourse.

c) The vaginal mucosa consists of a stratified epithelium adapted to stand up to friction. The mucosa has no glands, but instead is naturally lubricated by the mucous glands from the cervix. Large amounts of glycogen are released from the mucosa which is broken down (anerobically) by bacteria naturally found there which results in the formation of lactic acid which produces a natural acidic pH within the vagina.  The acid pH will help keep the vagina free of infection, but can also kill sperm.  Sexually transmitted diseases are more common among sexually active teens because because vaginal fluids in teens tends to be alkaline.   Certain mucosal cells (dendritic cells) act as antigen-presenting cells and are thought to provide the route of HIV transmission from an infected male to the female during sexual intercourse.

d) The mucosa near the distal vaginal orifice forms an incomplete partition called the hymen in virgin females. The hymen is very vascular and tends to bleed when it bleeds when females have intercourse for the first time.

e) The vaginal fornix is a vaginal recess formed where the upper end of the vaginal canal surrounds the cervix of the uterus and is divided into the lateral, anterior, and a deeper posterior fornix.

The External Genitalia (vulva) (pudendum)

a) The mons pubis is a fatty, rounded area overlying the pubic symphysis, and is covered by hair (pubic hair) after puberty. Two elongated outer large folds run posteriorly from the mons pubis and are called the labia majora. The labia major homologous to the male scrotum. This means that it has the same origin as the scrotum (both are derived from the same embryonic tissue), but a different function. 

b) Within the labia majora are found the two inner folds called the labia minora. The labia minora unlike the labia majora are much thinner and are not covered by skin.  The labia minora are homologous to the ventral penis. The labia minora enclose a recess called the vestibule which contains the external opening of the urethra anteriorly, and posteriorly the external opening of the vagina. The greater vestibular glands  (homologous to the bulbourethral glands of males) are on each side of the vaginal opening within the vestibule. These glands release mucus into the vestibule and help to keep it moist and lubricated, facilitating intercourse.

c) The clitoris is located just anterior to the vestibule and consists of a small protruding structure composed of erectile tissue, and is homologous to the male penis. The clitoris is surrounded anteriorly by a fold of skin called the prepuce of the clitoris formed by the junction of the labia minora folds.

d) A diamond shaped region called the perineum located between the pubic arch anteriorly , the coccyx posteriorly, and the ischial tuberosities  laterally.

The Mammary Glands

a) Present in both sexes, but only functional in females mammary glands are actually modified sweat glands and part of the integumentary system. A ring of pigmented skin called the areola is found surrounding each nipple. The areola is slightly bumpy due to the presence of large sebaceous glands which produce sebum that reduces chapping and cracking of the skin of the nipple. The nipple can become erect by tactile stimulation, and by exposure to cold.

b) Internally 15 to 20 lobes radiate around and open at the nipple. The lobes are padded and separated from each other by fibrous connective tissue and fat. The interlobar connective tissue forms suspensory ligaments that attach the breast to the underlying muscle fascia and to the overlying dermis. The suspensory ligaments provide natural support for the breasts. Within the lobes are smaller units called lobules which contain glandular alveoli that produce milk when the woman is lactating.  Milk is passed from them into the lactiferous ducts which open to the outside at the nipples Each duct has a dilated region called a lactiferous sinus where milk accumulates  during nursing.

Hormonal Regulation of the Ovarian Cycle (Figure 28.1)

The Uterine  (Menstrual) Cycle

a) A 28 day cycle divided into three stages: The Menstrual phase, Proliferative phase, and Secretory phase (figure 28.22 d)

b) The Menstrual phase (Days 1-5): On day one of this stage gonadotropin hormones (FSH and LH from the anterior pituitary gland) are rising and the ovarian hormones (estrogen and progesterone) are at their lowest levels. Then the thick functional layer of the endometrum detaches from the uterine wall accompanied by bleeding for 3-5 days, and by day 5 the growing ovarian follicles begin producing more estrogen.

b) The Proliferative phase (Days 6-14): Estrogen levels continue to rise and the basal layer of the endometrium generates a new functional layer which results in an increase in number of spiral arteries and glands  and the endometrium becomes thick and vascularized within the uterus.  Estrogens also induce the synthesis of progesterone receptors in the endometrial cells readying them for the the interaction with progesterone.  Rising estrogen levels then cause the mucus within the uterus to thin forming channels that facilitate the passage of sperm into the uterus.  Ovulation (release of the oocyte into the fallopian tube ) occurs in the ovary at the end of this stage on day 14  in response to the sudden release of LH from the anterior pituitary. LH also converts the ruptured follicle into the corpus luteum.

c) The Secretory phase (Days 15-28):  The endometrium prepares itself for the implantation of the embryo. During this time the corpus luteum produces progesterone which converts the functional layer into a secretory mucosa in which the spiral arteries to coil more tightly, and the uterine glands to enlarge, coil and begin secreting nutrients in the form of glycoproteins to sustain the embryo until implantation.   The increased progesterone levels also cause the cervical mucus to become more viscous again forming the cervical plug which acts to block the uterus from further sperm entry just in case the embryo has become implanted.  Rising progesterone (and estrogen)  levels also inhibit LH  release from the anterior pituitary gland.  If fertilization has not occurred, the corpus luteum begins to degenerate toward the end of the secretory phase as LH levels decline. Progesterone levels decline causing the  spiral arteries in the endometrium to begin to kink and go into spasms. This cuts off the nutrient and oxygen supply to the endometrial cells and they begin to die. The lysosomes within the cells begin to rupture and the cells begin to "self digest" and menstruation begins on day 28.  The functional layer will then slough off causing the first day of menstrual flow, and the menstrual cycle starts over on the first day again. If fertilization has occurred then the corpus luteum  is maintained by an LH like hormone released by the developing embryo so the corpus luteum continues to release progesterone which maintains the thickened mucosal layer of the uterus to which is attached an implanted embryo and no menstrual flow occurs on day 1 of the next menstrual cycle. 

Embryological and Fetal Events (page 1105) Determination of the Genetic Sex

PREGNANCY AND HUMAN DEVELOPMENT

 Fertilization.                                                                                                             a) The oocyte or egg is viable for 12 to 24 hours after ovulation on the 14th day of the menstrual cycle. Pregnancy can only normally occur one day following ovulation.  Sperm can live for 24 to 72 hours after ejaculation. For a pregnancy to occur coitus must occur no more than three days before ovulation and no later than 24 hours after ovulation.

b) Millions of sperm are then deposited into the vaginal canal. Only a few thousand sperm (or as low as 200) actually reach the ovum. Many leak out of the vagina , some are destroyed in the acidic environment of the vagina, and  many are separated by the strong muscular contractions of the uterus if they make it this far. 

c) Before the sperm can fertilize the ooccyte they must undergo a process called capacitation. Anterior to the sperm nucleus there is a capsule containing enzymes called the acrosome.  The acroscomal membrane is very tough from the cholesterol present in them and are unable to release their hydrolytic enzymes until the membrane loses its "toughness" through a process called capacitation. Then their acrosomes become so fragile that they will release their enzymes simply by bumping into the oocyte. The mechanism by which capacitation occurs is not yet known.

d) In order to fertilize the oocyte the sperm must break through two layers of cells that surround the oocyte.  The outermost layer is called the corona radiata and the innermost layer is the zona pellucida.  Hundreds of acrosomes must rupture and release their enzymes to break through so that one sperm will be allowed entry to fertilize the oocyte.

e) Once a sperm enters into the oocyte it loses its tail and migrates to the center of the oocyte. The oocyte (still undergoing meiosis) completes meiosis II, by ejecting the second polar body.  The ovum and sperm nuclei then swell becoming male and female pronuclei and approach each other as a mitotic spindle develops between them.  The pronuclei membranes then rupture, releasing their chromosomes into the immediate vicinity of the spindle.  The spindle which is forming is from the last and final stage of meiosis II in which the fourth and final polar body is formed.  The true moment of fertilization occurs as the maternal chromosomes from the last division and the paternal chromosomes combine  and produce the diploid zygote ( the name for a fertilized egg).

Preembryonic Development

a) This process begins with the zygote (fertilization) and continues as the preembryo travels down the uterine tube and into the uterus where implantation occurs. It begins as the zygote begins to undergo a series of mitotic divisions called cleavage.   Each mitotic division results in the original number of cells doubling after each division.  The cells divide so fast that the daughter cells have little time to grow after each division and as a result become smaller and smaller. The cells produced have a high surface to volume ratio which enables them to take up nutrients and oxygen as well as disposing of wastes at a higher rate than larger cells. It also provides a large number of cells to serve as building blocks for constructing the embryo.

b) The first cleavage division produces two identical cells 36 hours after fertilization and are called blastomeres. These two divide and produce four, then those four divide again to produce eight  and so on.  By 72 hours a berry shaped cluster of 16 or more cells called a morula has been formed while it is still being transported to the uterus through the uterine tube.

c) By the fourth or fifth day after fertilization, the preembryo consists of about 100 cells and is floating freely in the uterus. The zona pellucida now starts to break down and the inner structure called the blastocyst escapes from it.  The blastocyst  (blastula) is a fluid-filled hollow sphere composed of a single layer of large , flattened cells called trophoblast cells and a small cluster of rounded cells, called the inner cell mass at one side. Trophoblast cells will take place in placenta formation, and the inner cell mass will become the embryonic disc which forms the embryo proper.

Implantation

a) Implantation occurs after the embryo has been floating freely in the uterus for two to three days, receiving nourishment from the uterine secretions. Implantation begins  between six to seven days after ovulation.

b) The outer layer of the embryo is called the trophoblast and as the embryo floats around testing the endometrium for the "window of implantation" which is a place on the uterus where the endometrium is properly prepared. It can implant high or low in the uterus depending upon which part of the endometrium has obtained the proper levels of ovarian hormones.

c) That part of the trophoblast which overlies the inner cell mass is the part of the embryo which attaches to the endometrium.  These trophoblast cells then begin secreting enzymes and growth factors against the endometrial surface which quickly becomes red  and thickened.   The uterine blood vessels have become more open increasing the blood flow to the area producing an inflammatory response.  Lymphocytes, natural killer cells, and macrophages invade the area as if it were an infection.

d) The trophoblast then forms two distinct layers.  The cells in the inner layer are called the cytotrophoblast and each cell retain their plasma membrane. The cells in the outermost layer are called the syncytiotrophoblast each lose their individual cell membrane and produces a multinucleated mass of tissue.  It protrudes into the endometrium and digests any uterine cell that it contacts. The blastocyst "burrows" into the endometrial lining as it is being digested by the syncytiotorphoblast, eventually being surrounded by a pool of blood, and covered over by dividing endometrial cells. The embryo has been planted very much like one would plant a seed in a garden.

e) Implantation takes about a week and is completed around the fourteenth day of ovulation.  The trophoblast cells have been secreting an LH-like hormone called human chorionic gonadotropin (hCG) to maintain the corpus luteum causing it to continue secreting progesterone and estrogen and therefore preventing the breakdown of the endometrium and menstruation.   The chorion which develops from the trophoblast after implantation continues the release of the hormone   for the early part phase of development.  This hormone (hCG) is detectable in the mother's bloodstream by the third week  of gestation (one week after fertilization) and will continue to rise until the second month declining sharply by the 4th month and remains at this lower value during the remainder of the pregnancy.  The placenta which forms during the second and third month produces progesterone and estrogen replacing the hCG during the rest of the pregnancy during which the corpus luteum has degenerated and the ovaries remain intact until after birth.

Placentation

a) The placenta is a temporary organ formed from embryonic (trophoblast) cells and from maternal (endometrial) tissues.  This begins when the trophoblast gives rise to a layer of extrembryonic mesoderm on its inner surface which becomes the chorion.   The chorion develops chorionic villi which penetrate into the blood stream of the mother.  The villi then become full of blood vessels and extend to the embryo forming the umbilical arteries and vein.  Large blood-filled lacunae, or intervillus spaces form in the stratum functionalis of the endometrium. The villi are then immersed within maternal blood in these spaces.

b) The part of the endometrium that lies between the chorionic villi and the stratum basalis becomes the decidua basalis whereas that surrounding of the uterine cavity face of the implanted embryo forms the decidua capsularis. Together the chorionic villi and the decidua basalis form the placenta.

c) The fetal side of the placenta is slick and smooth and contains the umbilical cord whereas the maternal side is bumpy revealing the shape of the chorionic villus masses.  The decidua capsularis expands to surround the growing fetus, and as the embryo continues to grow the villi in the dicidua  capsularis are compressed and degenerate, while the villi in the decidua basalis increase in number and branching.

d) The placenta is completely formed at the end of the third month of pregnancy  and becomes functional as  a nutritive, respiratory, excretory and endocrine organ.

e) Under normal conditions the placenta will continue to secrete estrogens and progesterone throughout the pregnancy increasing the blood levels of these hormones encouraging growth and further development  of the mammary glands readying them for lactation.  Under abnormal conditions during which the placenta is producing lower  inadequate amounts of these hormones then the endometrium begins to degenerate and the pregancy is aborted.  Oher hormones produced by the placenta are human placental lactogen, human chorionic thyrotropin, and relaxin. 

Embryonic Development

EMBRYONIC MEMBRANES

a) The embryo is also going through various stages of development during implantation and the formation of the placenta.  Embryonic membranes first of all begin to form. The amnion forms from cells from the epiblast into a transparent membraneous sac. The amnion eventually will completely surround the embryo. Also called the amnionic sac it becomes filled with a fluid called amniotic fluid which provides a constant homeostatic environment for the embryo along with protecting it from physical trauma. The amniotic membrane also prevents the embryo from fusing together and aids musculoskeletal  development by allowing freedom of movement.  Amniotic fluid is initially derived from the maternal bloodstream, until the fetal kidneys become functional at which time fetal urine contributes to the amniotic fluid volume. 

b) The yolk sac then forms from cells of the hypoblast and hangs from the ventral surface of the embryo with the amniotic sac extending from the dorsal surface of the embryo.  In other animals the yolk sac contains stored food for developing embryos which do not derive nutrients directly from their mother's bloodstream.  In humans  the yolk sac contains very little food because the placenta has taken care of the nutritive functions of the embryo. The human yolk sac forms part of the gut (digestive tube), produces the earliest blood vessels, and is the source of primordial germ cells that migrate into the embryo's body to seed the gonads.

c) The allantois is an extension of the caudal end of the yolk sac. In other animals that hatch from eggs the allantois is a disposal site for solid metabolic wastes.  In humans the allantois forms into the umbilical cord that links the embryo with the placenta, and becomes part of the urinary bladder. The umbilical cord eventually will form a core of connective tissue (Wharton's jelly) , the umbilical arteries, and vein, and is covered externally by the amniotic membrane.

d) The chorion which helped to form the placenta is the outermost membrane enclosing the body of the embryo and all other membranes.

GASTRULATION   

a) During the third week the two layered embryonic disc forms into a three layered embryo in which the three primary germ layers - ectoderm ,mesoderm, and endoderm - are present. This is a process called gastrulation. It first begins when a primitive streak (a raised groove) appears on the dorsal surface of the embryonic disc and establishes the longitudinal axis of the embryo.  Epiblast cells first  migrate medially into the primitive streak and form the endoderm, then other epiblast cells push laterally between the cells forming the mesoderm.  Cells remaining on the embryo's dorsal surface form the ectoderm.  The mesodermal cells immediately beneath the primitive streak aggregate and form a rod of mesodermal cells which is called the notochord.  The notochord is one of the three characterisics of all organisms in the phylum chordata (includes all vertebrates). The notochord will eventually form into the skeletal system during embryonic development in all vertebrates including humans.

b) Each of the three primary germ layers will serve as the primitive tissues from which all body organs and systems will develop.  The ectoderm will form the nervous system, and the skin epidermis; the endoderm forms the epithelial linings of the digestive, respiratory, and urogenital systems, and associated glands; the mesoderm will form the muscular system, circulatory system, skeletal system, urogenital system and other derivatives(table 29.1).  Both ectoderm and endoderm are considered epithelia and mesoderm is a mesenchyme which is a name for any embryonic tissue with star-shaped cells that are free to migrate widely within the embryo.

DIFFERENTIATION  OF THE GERM LAYERS

I) The ectoderm

A) Following gastrulation is a process called organogenesis which is the formation of body organs and organ systems. Organogenesis begins with a process called neurulation which is the differentiation of the ectoderm which gives rise to the brain and spinal cord. Chemical signals  from the notochord stimulate this process to occur.  The ectoderm overlying the notochord begins to thicken forming the neural plate and then begins to fold inward as a neural groove, which forms prominent neural folds as it deepens. The superior margins of the neural folds fuse by the twenty second day to form the neural tube which soon pinches off into the body. The anterior end of the tube becomes the brain the posterior end becomes the spinal cord.  The neural tube represents the second chordate characteristic: a dorsal hollow tubular nerve cord.  The neural crest cells migrate and give rise to the cranial, spinal, and sympathetic  ganglia and associated nerves as well as to the medulla of the adrenal glands and some of the connective tissues.

B) By the end of the second month all the major areas of the brain are recognizable and brain waves can be recorded (figure 12.4 - page 430). Most of the rest of the ectoderm develops into the epidermis of the skin along with other derivatives (table 29.1)   

II) The Endoderm

a) The embryo started off like a flat embryonic sheet consisting of the three primary germ layers in what is called a Trilaminar disc.  As it grows it folds into  a cylindrical body shape while the head and tail ends fold under. the folding which occurs at both ends progresses toward the central part of the embryo where the yolk sac and umbilical vessels protrude.  The tube of endoderm formed which encloses part of the yolk sac is called the primitive gut.  The primitive gut will form the epithelial lining of the gastrointestinal tract.  The organs of the GI tract including the pharynx, esophagus, etc become quickly visible as well as the oral and anal openings.  The mucosal lining of the respiratory tract, glands that derive from the endoderm also continue to form.  The glands form entirely from endodermal cells whereas only the mucosal lining  of the respiratory and digestive system only form from the endoderm.  Mesoderm forms the rest of their wall structure.  

III) The Mesoderm

a) The first thing formed from the mesoderm is the notochord (whose remnants persist in the intervertebral discs for twenty years).  After the formation of the notochord during embryonic development three aggregates of mesodermal cells appear on either side of the notochord.  The largest ones are called the somites.  There are forty pairs of somites present by the end of week four.  Small clusters of mesoderm called intermediate mesoderm  and lateral mesoderm are found on each side of the somites.

b) Each somite consist of three functional parts.  Cells of the sclerotome produce the vertebra and ribs, cells of the dermatome form the dermis of the skin in the dorsal part of the body, and cells of the myotome form the skeletal muscles of the neck, body trunk, and muscles of the limbs from the limb buds.

c) Other cells of the mesoderm include the intermediate mesoderm  which forms the gonads and kidneys, and the lateral mesoderm consisting of paired mesodermal plates: the somatic mesoderm and the splanchnic mesoderm.   The somatic mesoderm: helps to form the dermis of the skin in the ventral body region, the parietal serosa that lines the ventral body cavity, and the bones, ligaments, and dermis of the limbs. The splanchnic mesoderm forms the heart and blood vessels and most connective tissues of the body, as well as the smooth muscle, connective tissues, and literally the entire wall of the respiratory and GI tract.

d) Folding of the embryonic body forms the ventral body cavity called the coelom. At this time at the end of eight weeks the embryo is about 1 inch long.  All body systems appear and are developing, blood delivery to and from the embryo through the placenta is occurring at which point we now refer to the human as a fetus instead of an embryo.

FETAL CIRCULATION (Figure 29.13)

a) Special adaptations for embryonic and fetal life include:

---The umbilical vein which carries oxygen and nutrient rich blood from the placenta to the fetus---

---The umbilical arteries which carry waste-laden blood from the fetus to the placenta---

---The ductus arteriosus and the foramen ovale bypass the nonfunctional lungs---

---The ductus venosus allows blood to partially bypass the liver---

b) Changes in the cardiovascular system involve the occlusion of the umbilical vessels, as well as the ductus venosus, ductus arteriosus, and the foramen ovale.

DEVELOPMENTAL EVENTS OF THE FETAL PERIOD (table 29.2)

PREGNANCY

1) Anatomical changes in the mother include

----Chadwick's sign: The vagina develops a purplish hue due to the female reproductive organs becoming increasingly vascularized and engorged with blood---

----The areoloae of the breasts darken as they too engorge with blood and enlarge due to rising levels of estrogen and progesterone---

----Chloasma or the "mask of pregnancy" develop in some women involving an increased pigmentation of facial skin---

----The uterus continues to enlarge and as birth nears  it occupies most of the abdominal cavity which causes the abdominal organs to push against the diaphragm, the ribs to flare and the thorax to widen,---

----Lordosis which is accentuated lumbar curvature and backaches occur during the last few months of pregnancy.   This is due to the increasing bulkiness of the anterior abdomen which changes the woman's center of gravity---

----A waddling gait is obvious during pregnancy due to the production of a hormone called relaxin by the placenta.  Relaxin causes the pelvic ligaments and the pubic symphysis to relax, widen and to become more flexible.---

---A weight gain of about 29 pounds will occur during pregnancy due to an increase in blood volume, fetal and placental growth, and growth of the reproductive organs including the breasts----

2) Metabolic changes in the mother include...

---Increasing amounts of the hormone human placental lactogen (hPL), also called human chorionic somatomammotropin (hCS) are secreted from the placenta works with estrogens and progesterones to stimulate the breasts for lactation.  In addition hPL promotes growth of the fetus and exerts a glucose-sparing effect in the mother. Consequently, maternal cells metabolize more fatty acids and less glucose than usual, sparing glucose for use by the fetus-------

------Human chorionic thyrotropin (hCT) is also released by the placenta.  This hormone which is a glycoprotein is similar to thyroid stimulating hormone of the anterior pituitary . hCT activity increases the raste of maternal metabolism throughout the pregnancy causing hypermetabolism.  Plasma levels of parathyroid hormone and activated vitamin D rise ensuring that the developing embryo has adequate calcium to form bones.--

3) Physiological changes in the mother include...

--- Morning sickness  or nausea occurs during the first few months of pregnancy because the body is not yet become adapted to the rising levels of progesterone and estrogen----

---Heartburn (reflux of stomach acid) can occur because the esophagus is displaced and the stomach is crowded by the growing uterus---

----Constipation occurs because motility of the digestive system declines during pregancy---

---Frequent urination occurs because the kidneys are producing more urine due to fetal metabolic wastes. The uterus also compresses the urinary bladder  as it continues to grow resulting in more frequent, urgent, and sometime uncontrollable urination (stress incontinence.----

---Nasal stuffiness and nosebleeds often occur because the response that the nasal mucosa has to estrogens---

----Increase in vital capacity and respiratory rate occur often with hyperventilation---

----Residual volume declines and many women exhibit dyspnea or difficulty in breathing during the later stages of pregnancy---

---Blood volume increases by 25 to 40% by the thirty second week due to increase in formed elements and plasma volume to accommodate the needs of the fetus.  The increase in blood volume is a safeguard against blood loss during birth.---

---Blood pressure and and pulse rate increase causing a rise in cardiac output by 20-40%. This helps to propel the greater circulatory volume around the body. Because the uterus presses on the pelvic blood vessels, venous return from the lower limbs may be impaired, resulting in varicose veins.----

PARTURITION (BIRTH)

Initiation of Labor:

--Estrogens reach their highest level.  Rising levels of the hormone adrenocortical hormones (especially cortisol) secreted by the fetus  stimulate the placenta to release large amounts of estrogens as well as estrogens being released from the corpus luteum in the ovaries---

---The increase in the estrogens being released by the placenta stimulate the myometrial cells of the uterus to form abundant oxytocin receptors.  The increase in estrogens also tend to inhibit progesterone's effect on the uterine muscle causing the myometrium to become weak and irritable and causing weak, irregular uterine contractions to occur.   These contractions result in a condition called Braxton Hicks contractions, or false labor.---

---Oxytocin is then released by certain cells of the fetus which act upon the placenta to release prostaglandins. Both hormones are powerful uterine muscle stimulants and since the uterus is highly sensitive to oxytocin by the formation of the oxytocin receptors contractions become more frequent and the emotional and physical stresses activate the mother's hypothalamus to release more oxytocin from the posterior pituitary gland. True labor then begins due to the elevated levels of oxytocin and prostoglandins.  A positive feedback mechanism is used to stimulate even more oxytocin from the posterior pituitary.  Greater contractions cause the release of more oxytocin which cause greater contractile forces, and the extra contractile forces release more oxytocin and so on.  Fetal fibronectin which is an adhesive protein which acted to stick the fetal and maternal tissues together changes to a lubricant just before labor begins.---

---Premature birth can occur if oxytocin and prostaglandins are initiated too soon, and hindering either hormone can also inhibit the onset of labor.  Ibuprofen is an example of an antiprostaglandin drug which can be used to prevent preterm births.----

STAGES OF LABOR

1) Dilation Stage. Weak contractions begin about 15-30 minutes apart , lasting for about 10-30 seconds in the upper part of the uterus and move downward toward the vagina. The contractions spread to the lower uterine segments and the infant's head is forced against the cervix with each contraction causing the cervix to soften, become thinner and to dilate.  The amnion will soon rupture releasing the amniotic fluid, an event commonly called "breaking the water".  A process called engagement occurs when the infant's head enters the true pelvis.  The baby's head will turn so that its greatest dimension is in the anteroposterior line as it begins to move through the birth canal.    This is the longest stage of labor and lasts for 6-12 hours and continues until the cervix is fully dilated by the baby's head

2) Expulsion Stage.  This stage lasts from full dilation to delivery.  Contractions are occurring every 2-3 minutes  and last for about a minute by the time the cervix is fully dilated. This stage can last up to two hours but is typically only 50 minutes in a first birth and 20 minutes in subsequent births. A process called crowning occurs when the largest dimensions of the head is distending the vulva.  A procedure called an episiotomy may be performed  during which an incision is made to widen the vaginal orifice to prevent or reduce tissue tearing during expulsion.  Once the baby passes through the perineum it's head will extend and the rest of the body comes out much easier.  The baby normally  exits the mother's body in a head first or vertex presentation. The skull acts as a wedge to dilate the cervix and the head first position allows the baby to be suctioned free of mucus and to breathe even before it exits the birth canal.  Once the baby exits the birth canal the umbilical cord is clamped and cut.  Breech (buttocks first)   and other nonvertex births make delivery require the use of forceps to deliver the baby.  Such births also require more time to remove the mucus from the mouth of the baby to enable it to start breathing.

3) Placental Stage. This involves the delivery of the placenta and its attached fetal membranes (after birth) and occurs within 30 minutes  after the birth of the infant.  Strong uterine contractions continue after childbirth which compress uterine blood vessels which results in less bleeding, and the detachment of the placenta from the uterine wall.  The afterbirth is easily removed by pulling on the umbilical cord.  It is important to remove all placental fragments in order  to prevent postpartum bleeding (continued uterine bleeding) after delivery. The number of blood vessels in the severed umbilical cord are counted afterward because the absence of one of the umbilical arteries  is often associated with cardiovascular disorders in infants.

EXTRAUTERINE LIFE

---All of the special circulatory adaptations  are occluded within 30 minutes after birth except for the foramen ovale which usually takes about a year.  The flap of the foramen ovale "never" fuses in about 1/4 of all people, but normal blood pressure in the left atrium pushes it shut.  Failure of the ductus arteriosus or foramen ovale to close can result in congenital heart defects.   The greater parts of the umbilical arteries and veins close and turn into fiber. The proximal parts of the umbilical arteries persist as the superior vesical arteries which supply the urinary bladder while their distal parts become the medial umbilical ligaments.  The remnant  of the umbilical vein becomes the round ligament of the liver, or the ligament teres. The ductus venosus collapses  and is converted into the ligamentum venosum on the under side of the liver.  The pulmonary shunts close as the blood pressure on the left side of the heart increases and the blood pressure of the heart on the right side decreases.  The foramen ovale as mentioned is pushed to the shut position and it fuses shut forming a slight depression we now call the foramen ovalis.  The ductus arteriosus also collapses and is converted into the ligamentum arteriosum  which connects the pulmonary trunk.--

---At about 1 to 5 minutes after birth the infant's physical status is observed based on five signs: heart rate, respiration, color, muscle tone, and reflexes (tested by slaps on the feet). Each observation is given a score from 0 to 2 and the total is called the Apgar score. An Apgar score of 8-10 indicates a healthy baby. Respiration rate for example should be about 45 breathes per minute during the first two weeks and then gradually declines to normal levels.  Surfactant production occurs within the last months of prenatal life, and premature births may require respiratory assistance using a ventilater until their lungs are fully mature.---

---The transitional period lasts from 6-8 hours after birth.  When the baby takes the first breath he/she is awake and alert for about 30 minutes. During this time, heart rate increases above the normal infant range of 120 to 160 beats per minute, respiration is more rapid and irregular, and body temperature falls during the first thirty minutes.  After 30 minutes, activity of the baby decreases and the baby sleeps for 3 hours or so. Then a second period of activity occurs during which the baby gags and regurgitates mucus and debris.  After this the infant sleeps again and then stabilizes, with waking periods (dictated by hunger) occurring every 3-4 hours.---

LACTATION

--Lactation is the production of milk by the mammary glands.  Near the end of pregnancy rising levels of the placental hormones ( estrogens, progesterones, and lactogen) stimulate the pituitary gland to release prolactin-releasing hormone (PRH) which causes the anterior pituitary gland to secrete the hormone prolactin.  True milk production begins after about 2 - 3 days.  During the delay a yellowish fluid called colostrum is secreted. Colostrum has less lactose than milk and almost no fat, but it contains more protein, vitamin A , and minerals than milk.  Colostrum is rich in IgA antibodies.  The IgA antibodies which are resistant to digestion in the stomach may help to protect the infant's digestive tract from bacterial infection, and can also be absorbed by the digestive system into their bloodstream to provide even more immunity.----

---Prolactin release eventually slows down  after birth and continual milk production depends upon mechanical stimulation of the nipples by the suckling infant. Mechanoreceptors in the nipple send afferent impulses to the hypothalamus  for the continual secretion of PRH  and prolatin.  The same impulses also stimulate the hypothalmic release of oxytocin from the posterior pituitary gland which causes the let-down reflex which is the actual ejection of milk from the mammary glands.---

ADVANTAGES OF BREAST MILK

1) Its fats and iron are better absorbed and its amino acids are metabolized more efficiently than those of cow's milk

2) Besides IgA  and other immunoglobins it has a host of other beneficial chemicals, including complement, lysozyme, interferon, and lactoperoxidase, that work to protect infants from from infections.

3) Mother's milk also contains interleukins and prostaglandins   that prevent overzealous inflammatory responses  and a glycoprotein that deters the ulcer-causing bacteria (H. pylori) from attaching to the stomach mucosa.

4) Its natural laxative effect helps to cleanse the bowels of meconium, a tarry green-black past containing  sloughed-off epithelial cells, bile, and other substances.  Clearing merconium as quickly as possible helps to prevent physiological jaundice (provides a route for the release of bilirubin from the body as does feces later on) and encourages bacteria which is the source of vitamin K and B vitamins to colonize the large intestine.