Female Reproductive System

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I. ADULT OVARY (CORTEX) contains follicles in various stages of development, including the primordial follicle, primary follicle, secondary follicle, and Graafian follicle.

Follicles are composed of an oocyte, follicular cells, and thecal cells (Table 24-1).

II. CORPUS LUTEUM is a temporary endocrine gland. Its formation is dependent on luteinizing hormone (LH).

A. Development. Corpus luteum develops from the granulosa cells and theca interna cells of the Graafian follicle after the secondary oocyte is ovulated through a process called luteinization (i.e., cells develop the c"r>acity to produce steroid hormones).

1. Granulosa lutein cells synthesize and secrete progesterone. Progesterone maintains the endometrium of the uterus in the secretory (luteal) phase so that implantation and nutritional support of the blastocyst may occur. Mifepristone is a drug that binds to progesterone receptors and blocks progesterone action, thereby-inducing early abortion.

2. Theca lutein cells synthesize and secrete estrogen and estrone.

B. Effect of fertilization

1. If fertilization occurs, the corpus luteum enlarges and becomes the predominant source of steroids needed to sustain pregnancy for approximately 8 weeks. Thereafter, the placenta becomes the major source of rhe steroids required.

2. If fertilization does not occur, the corpus luteum regresses and forms a corpus albicans.

III. UTERINE TUBES are the site of fertilization.

A. Uterine rubes are lined by two types of cells.

1. Nonciliated cells secrete a nutrient-rich medium for the nourishment of the sperm and preimplantation embryo.

2. Ciliated cells have cilia that beat toward the uterus. The rate of ciliary beat is influenced by progesterone and estrogen, and they assist in transport of the preimplantation embryo to the uterus.

B. Clinical consideration. Salpingitis (acute and chronic) is a bacterial infection (most commonly gonococcus) of the uterine tube with acute inflammation (neutrophil infiltration) or chronic inflammation that may lead to scarring of the uterine tube, which predisposes affected women to ectopic tubal pregnancy.

Table 24-1

Development of the Ovarian Follicle

Stage of Follicle

Oocyte

Follicular Cells

Thecal Cells

Primordial

Primary oocyte (46, 4N) Arrested in prophase of meiosis 1

Squamous cells: 1 layer

Fibroblasts

Primary

Primary oocyte (46, 4N) Arrested in prophase of meiosis 1

Granulosa cells: 1 layer

Fibroblasts

Secondary Primary oocyte (46, 4N) Arrested in prophase of meiosis I i Zona pellucida present

dependent

Graafian Secondary oocyte (23, 2N) Arrested in metaphase of meiosis II Zona pellucida present

Granulosa cells: Multiple layers Secrete estrogen by aromatase conversion of androgens from theca interna FSH and LH receptors present

Theca interna: Secrete androgens LH receptors present

Theca externa:

Fibrous and vascular

FSH = follicle-stimulating hormone; LH = luteinizing hormone.

IV. UTERUS

A. Endometrium consists of simple columnar epithelium, which invaginates into the endometrial stroma to form endometrial glands. The endometrium can be divided into two layers.

1. The basal layer regenerates the functional layer each month during the menstrual cycle. The basal layer is never sloughed off.

2. The functional layer undergoes alterations during the menstrual cycle. The functional layer is sloughed off each month during menses.

B. The menstrual cycle is a series of phases that repeats ideally every 28 days.

1. The menstrual phase (days 1-4) is characterized by the necrosis and shedding of the functional layer of the endometrium. Spiral arterioles constrict episodically for a few days and finally constrict permanently, resulting in ischemia that leads to necrosis of endometrial glands and stroma. The spiral arterioles subsequently dilate and rupture, resulting in hemorrhage that sheds the necrotic endometrial glands and stroma.

2. The proliferative (follicular) phase (days 4-15) is characterized by the regeneration of the functional layer of the endometrium from the devastating effects of the menstrual phase. This phase is controlled by estrogen sccretcd by the granulosa cells of the secondary and Graafian follicle. Epithelial cells and fibroblasts of the basal layer of the endometrium regenerate to form straight endometrial glands and stroma, respectively.

3. The ovulatory phase (days 14-16) is characterized by ovulation of the secondary oocyte arrested in metaphase of meiosis 11 that coincides with peak levels of LH (LH surge).

4. The secretory (luteal) phase (days 15-25) is characterized by the secretory activity of the endometrial glands. This phase is controlled by progesterone secreted by the granulosa lutein cells of the corpus luteum. The endometrial glands become modified to convoluted endometrial glands with secretion product within their lumen.

5. The premenstrual phase (days 25-28) is characterized by ischemia due to reduced blood flow to the endometrium. This phase is controlled by the reduction in progesterone and estrogen as the corpus lutcum involutes. As the endometrial glands begin to shrink, the spiral arterioles are compressed, thereby reducing blood flow and causing ischcmic damage.

C. Myometrium consists of smooth muscle cells that are connected by gap junctions and contract on stimulation by oxytocin and prostaglandins at parturition. The myometrium contains the stratum vasculare, which is highly vascular and is the source of the endometrial blood supply.

D. Perimetrium consists of connective tissue covered by peritoneal mesothelium.

E. The intricate coordination between the hypothalamus, adenohypophysis, ovaries, and endometrium of the uterus results in the menstrual cycle (Figure 24-1).

F. Clinical considerations

1. Endometriosis is the presence of endometrial glands in abnormal locations (e.g., ovary, uterine ligaments, pelvic peritoneum), causing infertility, dysmenorrhea, and pelvic pain.

2. Leiomyoma is a very common benign tumor derived from smooth muscle within the myometrium.

3. Amenorrhea is the absence of menstruation.

a. Primary amenorrhea is the complete absence of menstruation in a woman from puberty.

b. Secondary amenorrhea is the absence of menstruation for at least 3 months in a woman who previously had normal menstruation.

(1) Causes. The most common cause of secondary amenorrhea is pregnancy, which can be determined by assaying urine human chorionic gonadotropin (hCG). Other pathologic causes of secondary amenorrhea include hypothalamic/pituitary malfunction (e.g., anorexia nervosa), ovarian disorders (e.g., ovariectomy), and end-organ disease (e.g., Ash-erman syndrome, in which the basal layer of the endometrium has been removed by repeated curettages).

(2) Diagnosis. These causes are evaluated clinically by assaying serum follicle-stimulating hormone (FSH) and LH levels along with a progesterone challenge. Bleeding after a progesterone challenge indicates that the endometrium was primed by estrogen, thereby indicating that the hypothalamic/pituitary axis and the ovaries are functioning normally. The results of such clinical evaluations are indicated in Table 24-2.

Table 24-2

Results of Clinical Evaluations for Secondary Amenorrhea

Table 24-2

Results of Clinical Evaluations for Secondary Amenorrhea

Serum FSH

Serum LH

Bleeding After Progesterone Challenge

Anorexia nervosa

Low

Low

No

Ovariectomy

High

High

No

Asherman syndrome

Normal

Normal

No

FSH = follicle-stimulating hormone; LH = luteinizing hormone.

FSH = follicle-stimulating hormone; LH = luteinizing hormone.

Hypothalamus

GnRH

Figure 24-1. Hormonal control of the menstrual cyclc. The hypothalamus secretes gonadotropin-relcasing hormone (GnRH). In response to GnRH, the adenohypophysis secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In response to FSH, the development of a secondary follicle to a Graafian follicle is stimulated in the ovary. The granulosa cells within the secondary follicle and Graafian follicle secrete estrogen (E). In response to estrogen, the endometrium of the uterus enters (he proliferative phase. In response to LH (LH surge), ovulation occurs. After ovulation, the granulosa lutein cells of the corpus luteum secrete progesterone (P). In response to progesterone, the endometrium of the uterus enters the secretory phase. Conditions that impair the secretion of GnRH from the hypothalamus will prevent the secretion of FSH that is necessary for follicle development and will resulr in inferriliry. In such cases, the drug clomiphene (an estrogen receptor antagonist) is used to increase GnRH secretion. In patients with polycystic ovary syndrome, increased LH secretion from the adenohypophysis stimulates excessive production of androgens by the theca interna cells of secondary and Graafian follicles, resulting in numerous atretic or cystic follicles.

Figure 24-1. Hormonal control of the menstrual cyclc. The hypothalamus secretes gonadotropin-relcasing hormone (GnRH). In response to GnRH, the adenohypophysis secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In response to FSH, the development of a secondary follicle to a Graafian follicle is stimulated in the ovary. The granulosa cells within the secondary follicle and Graafian follicle secrete estrogen (E). In response to estrogen, the endometrium of the uterus enters (he proliferative phase. In response to LH (LH surge), ovulation occurs. After ovulation, the granulosa lutein cells of the corpus luteum secrete progesterone (P). In response to progesterone, the endometrium of the uterus enters the secretory phase. Conditions that impair the secretion of GnRH from the hypothalamus will prevent the secretion of FSH that is necessary for follicle development and will resulr in inferriliry. In such cases, the drug clomiphene (an estrogen receptor antagonist) is used to increase GnRH secretion. In patients with polycystic ovary syndrome, increased LH secretion from the adenohypophysis stimulates excessive production of androgens by the theca interna cells of secondary and Graafian follicles, resulting in numerous atretic or cystic follicles.

4. Menorrhagia is cxcessivc bleeding at menstruation in either the amount of blood or number of days. It is usually associated with a leiomyoma.

5. Dysmenorrhea is excessive pain during menstruation. It is commonly associated with endometriosis and an increased level of prostaglandin F in the menstrual fluid.

6. Metrorrhagia is bleeding that occurs at irregular intervals. It is commonly associated with cervical carcinoma or cervical polyps.

7. Prepubertal bleeding is bleeding that occurs before menarche. It is commonly associated with vaginitis, infection, sexual abuse, or embryonal rhabdomyosarcoma.

8. Postmenopausal bleeding occurs approximately 1 year after the cessation of the menstrual cycle. It is commonly associated with malignant tumors of the uterus.

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