03 September 2016

Lecture #12: THE GONADS: FEMALE REPRODUCTIVE ORGAN





THE FEMALE REPRODUCTIVE ORGAN


Function of the female reproductive system

1.      The function of the female reproductive system is to produce offspring and thereby ensure continuity of the genetic code.

2.      It produces eggs or female gametes, which each may unite with a male gamete to form the first cell of any offspring.

3.      It also can provide nutrition and protection to the offspring for up to several years after conception.


Structural plan of the female reproductive system

1.      Essential organs – gonads are the paired ovaries; gametes are ova produced by the ovaries – the ovaries are also internal genitals.

2.      Accessory organs

a.      Internal genitals – uterine tubes, uterus and vagina – ducts or duct structures that extend from the ovaries to the exterior

b.      External  genitals – the vulva


The Uterus

1.      Structure of the uterus

a.      Size and shape of the uterus

(1)   The uterus is pear–shaped and has two main parts – the cervix and the body.

b.      The wall of the uterus is composed of three layers

(1)   The inner endometrium
(2)   Middle myometrium
(3)   Outer incomplete layer of parietal peritoneum

c.       Cavities of the uterus – the cavities are small because of the thickness of the uterine walls

(1)   The body cavity’s apex constitutes the internal os and opens into the cervical canal, which is constricted at its lower end and forms the external os that opens into the vagina.

d.     The blood to the uterus is supplied by uterine arteries


2.      Location of the uterus

a.      The uterus is located in the pelvic cavity between the urinary bladder and the rectum.

b.      The position of the uterus is altered by age, pregnancy and distension of related pelvic viscera

c.       The uterus descends, between birth and puberty, from the lower abdomen to the true pelvis.

d.     The uterus begins to decrease in size at menopause.


3.      Function of the uterus

a.      The uterus is part of the reproductive tract and permits sperm to ascend toward the uterine tubes.

b.      If conception occurs, the offspring develops in the uterus

(1)   The embryo is supplied with nutrients by endometrial glands until production of the placenta

(2)   The placenta is an organ that permits the exchange of materials between the mother’s blood and the fetal blood but keeps the two circulations separate.

(3)   Myometrial contractions occur during labor and help push the offspring out of the mother’s body.

c.       If conception does not occur, outer layers of endometrium are shed during menstruation

(1)   Menstruation is a cyclical event that allows the endometrium to renew itself.


The Uterine tubes

1.      Uterine tubes are also called Fallopian tubes or oviducts

2.      Uterine tubes are attached to the uterus at its upper outer angles and extend upward and outward toward the sides of the pelvis

3.      Structure of the uterine tubes

a.      Uterine tubes consist of mucous, smooth muscle and serous lining

b.      Mucosal lining is directly continuous with the peritoneum lining the pelvic cavity

(1)   Tubal mucosa is continuous with that of the vagina and uterus, which means it, may become infected with organisms introduced into the vagina.

c.       Each uterine tube has three divisions

(1)   Isthmus
(2)   Ampulla
(3)   Infundibulum

4.      Function of the uterine tubes

a.      Uterine tubes serve as transport channels for ova and as the site of fertilization


The Ovaries

1.      Location of the ovaries

a.      The ovaries are nodular glands located on each of side of the uterus, below and behind the uterine tubes.

b.      Ectopic pregnancy – development of the fetus in a place other than the uterus.

2.      Microscopic structure of the ovaries

a.      The surface of the ovaries is covered by the germinal epithelium
b.      Ovarian follicles contain the developing female sex cells.
c.       Ovum – an oocyte released from the ovary

3.      Functions of the ovaries

a.      Ovaries produce ova – the female gametes
b.      Oogenesis – process that results in formation of a mature egg
c.       The ovaries are endocrine organs that secrete the female sex hormones (estrogens and progesterone)

The Vagina

1.      The vagina is a tubular organ located between the rectum, urethra and bladder.

2.      Structure of the vagina

a.      The vagina is a collapsible tube capable of distension, composed of smooth muscle, and lined with mucous membrane arranged in rugae.

b.      The anterior wall is shorter than the posterior wall because the cervix protrudes into its uppermost portion.

c.       Hymen – a mucous membrane that typically forms a border around the vagina in young pre–menstrual girls.

3.      Functions of the vagina

a.      The lining of the vagina stimulates the penis during sexual intercourse and acts as receptacle for semen.

b.      The vagina is the lower portion of the birth canal.

c.       The vagina is a transport for tissue shed during menstruation


The Vulva

1.      The vulva consists of the female external genitals; mons pubis, labia majora, labia minora, clistoris, urinary meatus, vaginal orifice and greater vestibular glands.

2.      Functions of the vulva

a.      The mons pubis and labia protects the clitoris and vestibule.

b.      Vestibular glands produce lubrication to reduce friction during intercourse.

c.       The clitoris contains sensory receptors that send information to the sexual response is of the brain.

d.     The vaginal orifice is the boundary between the internal and external genitals.


The Perineum

1.      The perineum is the skin–covered region between the vaginal orifice and the rectum.

2.      This area may be torn during childbirth


Regulation of secretion of ovarian hormone

1.      Ovarian cycle – ovaries from birth contains oocytes in primary follicles in which the meiotic process has been suspended. At the beginning of menstruation each month, several of the oocytes resume meiosis. Meiosis will stop again just before the cell is released during ovulation.

During the ovarian cycle, the uterus also undergoes cyclic changes (uterine cycle). The endometrial layer responds to the changes of the ovarian hormones and is the source of menstrual discharge if pregnancy does not occur. If pregnancy does occur, the endometrium participates in the formation of placenta.

2.      Endometrial cycle or menstrual cycle

a.      Menses – a periodic vaginal bleeding, resulting from shielding of the endometrial lining of the uterus.

b.      Post–menstrual phase

(1)   An early follicle called the primordial follicle is observed in the peripheral area in the ovarian cortex. It is composed of a primary oocyte that is surrounded by a single layer of follicular cells. Several primordial follicles differentiate into primary follicle.

(2)   The layer of follicular cells proliferates and forms a layer of granulosa cells that surrounds the primary oocyte.

(3)   Connective tissue surrounding the follicle then differentiates to form thecal cells.

(4)   The follicle becomes enlarged because the granulosa cell secrete a fluid that not only fills spaces between cells but also displaces the oocyte to one side, thus producing a large cavity in the center of the follicle. This follicle is known as secondary follicle.

(5)   The follicle further matures to become a Graafian follicle, and although several follicles begin this process, only follicle reaches the final stage. The rest degenerates.

(6)   The Graafian follicles produce a bulge in the outer surface of the ovary. The time required for the development of this mature follicle is approximately 14 days and this period is known as the follicular phase of the menstrual cycle.

c.       Ovulation – Graafian follicles ruptures and the ovum is expelled from it.

d.     Pre–menstrual phase

The Graafian follicle remaining in the ovary undergoes change and become known as a corpus luteum (yellow body). The thecal and granulosa cells undergo changes and secrete progesterone.


3.      Myometrial phase

If fertilization of the ovum does not occur, the corpus luteum ceases to secrete hormones and becomes non–functional and is known as the corpus albicans (white body). The time required for this process is about 14 days after ovulation and is known as the luteal phase of the menstrual cycle.


4.      Gonadotropic cycle

a.      The hypothalamus releases Gn–RH, which maybe controlled by dopamine (inhibitors) and norepinephrine (stimulator). The gonadotrope cells of the anterior pituitary release FSH, which in turn causes the proliferation of the granulosa cells in the ovary. FSH, therefore, is responsible for the early growth of the primary follicle. It may also influence the conversion of testosterone to estradiol, which takes place in the thecal cells. This estradiol that is produced causes the granulosa cells to form more FSH receptors, making them more sensitive to FSH. The rising levels of estradiol that occur in the early to mid–follicular phase inhibit the production of pituitary FSH. However, in the late follicular phase, rising levels of estradiol cause the pituitary to release LH. This surge of LH causes ovulation.

b.      The release of Gn–RH from the hypothalamus also causes the anterior pituitary to release LH. LH acts on the thecal cells of the ovary to induce the synthesis of androgens and ultimately estradiol. The estrogen produced diffuses into the granulosa cells. LH is necessary for the final follicular growth and ovulation and works synergistically with FSH. It influences the change of the granulosa cells into lutein cells and thus the production of progesterone. It has been postulated that progesterone may serve in the negative feedback mechanism for the LH release from the anterior pituitary.


The Cervical mucus

Cervical mucus is a complex secretion produced by the gland of the endocervix and it has the following characteristics:

1.      It is composed of 92 – 98% water and approximately 1% inorganic salts, of which NaCl is the main constituents

2.      The mucus also contains free simple sugars, polysaccharides, proteins and glycoproteins.

3.      Its pH is usually alkaline and ranges from 6.5 to 9.0

4.      Spinnbarkeit – is the property that allows cervical mucus to be stretched or drawn into a thread. Spinnbarkeit can be estimated by stretching a sample of mucus between 2 glass slides and measuring the maximum length of the thread before it breaks. At midcycle, spinnbarkeit usually extends 10cm.

5.      Ferning or arborization refers to the characteristic microscopic pattern cervical mucus forms when dried on a slide. Ferning results from the crystallization of inorganic salts around small and optimal amount of organic materials present in cervical mucus.


The Ovarian hormones

1.      Estrogens are synthesized by the thecal cells of the ovaries in female and small amounts are produced by the adrenal cortex in male and female and by the testes in male. The estrogen metabolites are

a.      Estradiol
b.      Estrone
c.       Estiol

2.      Progesterone is produced mainly by the granulosa (lutein) cells of the corpus luteum in female. It is also produced by the placenta in pregnancy, and small amount can be produced by the adrenal cortex. The main urinary metabolite is pregnanediol.

3.      Dehydroepiandrosterone (DHEA) is an androgen primarily derived from the adrenal gland. Its conjugation product DHEA–sulfate in plasma has replaced the 17–ketosteroid.

4.      Relaxin is polypeptide that has been extracted from the ovary. In certain animal species, it appears to play important at the time of parturition, causing relaxation of the pelvic ligaments and softening of the uterine cervix. It is found in ovary, blood and placenta. It also increases glycogen synthesis and water uptake by the myometrium and decreases its contractility.


Laboratory evaluation of ovarian function

1.      Urine estrogens to monitor development of the unborn child during pregnancy.

a.      Kober reaction involves heating a urine sample in a strong aqueous sulfuric acid solution containing hydroquinone. After cooling and dilution, the absorbance of the resulting reddish–brown color is measured and total estrogen concentration determined.

b.      Assay interferences

(1)   Falsely decreased: ampicillin, neomycin, hydrochlorothiazide

(2)   Falsely elevated: meprobamate, L–dopa, phenolphthalein

2.      Serum estradiol to monitor ovarian tumors. Decreased level may be found in primary and secondary ovarian failure as well as in adrenal gland malfunction.

Reference range:

a.      Female

Prepubertal                           4 – 12 pg/ml
Early follicular phase          30 – 100 pg/ml
Late follicular phase                        100 – 400 pg/ml
Luteal phase                         50 – 150 pg/ml
Post menopausal                 5 – 18 pg/ml

b.     Male

Prepubertal                           2 – 8 pg/ml
Adult                                      10 – 60 pg/ml


3.      Serum progesterone has been used primarily for the evaluation of fertility in females, in particular for the detection of ovulation.

Reference range:

a.      Male                                 0.12 – 0.3 ng/ml

b.      Female    

Menstrual cycle

      Follicular phase       < 1 ng/ml
      Luteal phase             5 – 20 ng/ml

Pregnancy

      1st trimester               20 – 50 ng/ml
      2nd trimester              50 – 100 ng/ml
      3rd trimester               100 – 400 ng/ml


4.      Serum DHEA – S is valuable for the assessment of adrenal cortical function.

Reference range:

a.      Adult males                    3.6 – 6.3 ng/ml (12.5 – 21.9 nmol/L)

b.      Females                           4.4 – 6.0 ng/ml (15.3 – 20.8 nmol/L)


Inhibitors of ovarian function

1.      Gn–RH – leuprolide, buserelin, nafarelin
2.      Tamoxifen
3.      Danazol
4.      Antiprogestins: Mifepristone, epostane
5.      Antiandrogens: Cyproterone, cyproterone acetate, ketoconazole


Clinical significance of Ovarian Function Test

1.      Female Infertility

a.      Uterine leimyonas, adenomas of smooth muscle cells, are the most common tumors of the uterus. If present, they can interfere with the implantation of a fertilized ovum

b.      Partial or total destruction of the endometrial lining of the uterus known as Asherman’s syndrome, also makes implantation impossible.

c.       Tubal abnormalities usually result in decreased patency of the lumen of the oviducts. This can be caused by chronic infections as well as endometriosis.

d.     Ovarian abnormalities usually result in anovulation, which is the failure to produce a mature ovum for fertilization. This condition may be caused by infections, tumors or polycystic ovary disease (PCOD).

e.      At the pituitary level, hypersecretion of prolactin (PRL) due to an adenoma may result in infertility. This condition is usually accompanied by amenorrhea and galactorrhea. Hypersecretion of PRL may also be seen in patients taking certain medications such as dopamine antagonists or in some cases of hypothyroidism.

f.        If the hypothalamus is not producing Gn–RH, ovulation will not occur. Tumors of the hypothalamus are rare causes of disruption of Gn–RH. More common causes include stress, weight loss, exercise and chronic illness.

2.      Hirsutism

Hirsutism in women is defined as excessive growth of hair in male distribution. The face, chest, abdomen and sacral regions are commonly affected. Hirsutism is associated with normal or moderately increased levels of testosterone.

Virilizaton on the other hand, is an abnormal development of the secondary male sex characteristics. These characteristics may include hirsutism but also hoarse voice, acne, clitoral enlargement and changes in body mass distribution. Virilization is caused by greatly increased levels of testosterone.

Causes of hirsutism

a.      Primary hyperandrogenemia

(1)   Congenital Adrenal Hyperplasia (CAH) is a genetic disorder characterized by the deficiency or absence of enzymes involved in the biosynthetic pathway for the production of cortisol. Since very little cortisol is produced, the pituitary gland releases ACTH to compensate. The adrenal gland is then stimulated and produces excessive amounts of the steroid hormones above the enzymatic block. This usually results in excessive androgen production.

(2)   Polycystic Ovary Disease (PCOD) linked to an abnormal release of LH by the pituitary. The hypersecretion of LH causes thecal hyperplasia in the ovary and thus increased androgen levels.

(3)   Tumors of the adrenal gland and ovary can produce massive amounts of androgens.


b.      Secondary hyperandrogenemia

(1)   Pituitary adenomas, testicular feminization, hypothyroidism and Type II Diabetes mellitus

(2)   Excessive secretion of ACTH, growth hormone and PRL from pituitary

c.       Idiopathic hirsutism is a genetically determined increased sensitivity of the hair follicle to androgens


3.      Amenorrhea

Amenorrhea is the absence of vaginal bleeding. Amenorrhea can be a physiologic process, such as occurs with pregnancy, or it can be pathologic. The pathologic causes of amenorrhea maybe either primary or secondary.

a.      Primary amenorrhea is defined as having no previous vaginal bleeding. Among healthy females, 99% have begun to menstruate by the age of 16. Signs of puberty, such as breast development and appearance of pubic hair, develop before menarch. If a female reaches the age of 14 without showing any signs of puberty or having begun to menstruate, the diagnosis of amenorrhea is made.

Causes of amenorrhea:

(1)   Chromosomal abnormalities like Turner’s syndrome (gonadal dysgenesis)

(2)   Congenital structural malformation like Mullerian agenesis which is the absence of uterus, fallopian tubes or vagina.

b.     Secondary amenorrhea is defined as the absence of menses for 6 months or for the equivalent three previous cycle intervals, whichever is longer.

Causes of secondary amenorrhea:

(1)   Weight loss, strenuous exercise, drugs and stress
(2)   Asherman syndrome
(3)   Primary hypothyroidism









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