Dr. Abdal-jabbar F. Al-Rubai'y, M.B.Ch.B, M.Sc, Ph.D (UK)

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1 The female reproductive system Oviducts: The oviducts are two muscular tubes of great motility, cm in length. It can be divided into 4 portions by gross inspection: The infundibulum: it lies next to the ovary and has fingerlike extensions called fimbriae. The ampulla: is the longest segment, about two third of the length. The isthmus: is the narrow, medial segment adjacent to the uterus. The intramural portion: which open into the interior of the uterus. The wall has three layers 1-Mucosa 2- Thick muscularis (inner circular and outer longitudinal layers of smooth muscles) 3- And serosa. There is no submucosa. The mucosa has longitudinal folds that are most numerous in the ampulla. In the intramural portion, the folds are reduced to small bulges in the lumen. The mucosa is composed of a simple columnar epithelium and a lamina propria composed of loose connective tissue. The epithelium contains two types of cells: ciliated cells and secretary cells. The cilia beat toward the uterus. At the moment of ovulation, the fimbriae come very close to the surface of the ovary to transport of the ovulated oocyte into the tube. Promoted by the muscular contraction and the activity of ciliated cells, the oocyte enters the infundibulum of the oviduct. The secretary cells produce nutritive material for the ovum. Estrogen stimulates ciliogenesis while progesterone increases the number of secretary cells. Unless the oocyte is fertilized, the oocyte remains viable for a maximum of about 24 hours. Several conditions may alter the integrity of the tubal transport system (like inflammation, the use of intrauterine device, surgical manipulation, tubal ligation) may result in ectopic pregnancy. 98% occur in uterine tube, the remaining sites are peritoneal cavity, ovaries, and cervix. Uterus: The uterus is a pear shaped organ that consists of a body (corpus) which lies above the internal os and the cervix which lies below the internal os. The dome shaped part of the body of the uterus is called the fundus. The wall of the uterus is relatively thick and is composed of three layers: serosa (perimetrium), the myometrium which is a thick tunic of smooth muscle, and the endometrium, or mucosa of the uterus (like ovarian tube, there is no submucosa).

2 Myometrium: The myometrium is composed of a three poorly defined layers of smooth muscle fibers separated by connective tissue. During pregnancy, the myometrium goes through a period of great growth as a result of both hyperplasia and hypertrophy of preexisting smooth muscle fibers and the differentiation of undifferentiated mesenchymal cells. The amount of connective tissue also increased. After pregnancy there is destruction of some smooth muscle cells, reduction in the size of others. The collagen produced during pregnancy enzymatically degraded by the cells which secrete it, then, the uterus is reduced in size almost to its prepregnancy dimensions. Endometrium: The endometrium lined with simple columnar epithelium which invaginates into the lamina propria (endometrial stroma) to form simple tubular glands that sometimes branch in their deeper portions. Its covering epithelial cells are mixture of ciliated and secretory simple columnar cells. The endometrial layer can be subdivided into two zones: 1- The basalis adjacent to the myometrium 2- The functionalis contains the remainder of the endometrial stroma and the glands, as well as the surface epithelium. Whereas the functionalis undergo profound changes during menstrual cycles, the basalis remain mostly unchanged. The blood vessels supplying the endometrium come from uterine artery which gives off 6-10 arcuate arteries which lie in the middle layer of the myometruim, from these vessels two sets of arteries arise to supply blood to the endometrium: straight arteries which supply the basalis, and spiral arteries supply both basalis and functionalis. The spiral arterioles give off several arterioles and often anastomose to form rich capillary bed. (see the figure below).

3 The vasculature of endometrium The menstrual cycle: Estrogens and progesterone control the organs of the female reproductive system. After puberty, the ovarian hormones, under the stimulus of the anterior lobe of the pituitary, cause the endometrium to undergo cyclic structural modifications during the menstrual cycle. The duration of the menstrual cycle is variable but averages 28 days. Menstrual cycle usually start between 9-14 years of age (average 12.7 years) and continue until about years (average 52.4 years). The beginning of the menstrual cycle is taken as the day when menstrual bleeding appears. The menstrual discharge consists of degenerating endometrium mixed with the blood from the ruptured blood vessels. The menstrual phase lasts 3-4 days on average. The next phases of the menstrual cycle are called the proliferative and secretary phase (luteal phase). The secretory phase begins at ovulation and lasts about 14 days. The duration of the proliferative phase is variable, 10 days on average.

4 Figure 7. Pituitary hormones control most ovarian functions. Follicle-stimulating hormone (FSH) stimulates follicular growth and synthesis of estrogen by the granulosa cells. Luteinizing hormone (LH) induces ovulation and transforms the granulosa layer and the theca interna into an actively secreting gland, the corpus luteum. Estrogen and progesterone produced in the ovary act on the hypothalamus, stimulating or inhibiting the liberation of gonadotropin-releasing hormone (GnRH). The proliferative, Follicular OR Estrogenic phase: The beginning of the proliferative phase coincides with the rapid growth of a small group of ovarian follicles, when their theca interna develops, these follicles begin to actively secrete estrogens. Estrogens act on the endometrium including cells proliferation and reconstituting the endometrium lost during menstruation. The endometrium is covered by a simple columnar epithelium. The glands are straight with narrow lumens. These cells gradually accumulate more cisternae of rough endoplasmic reticulum and the Golgi complex increase increases in size in preparation for secretory activity. This phase ends until 1 day after ovulation. At the end of the proliferative phase, the endometrium is 2-3 mm thick. The secretory, OR Luteal phase: The secretory phase starts 1-2 days after ovulation and result from the action of progesterone secreted by the corpus luteum. The epithelial cells begins to accumulate glycogen below their nuclei, glycoprotein secretory products dilate the lumens of the glands. The glands become highly coiled. The endometrium reach its maximumu thickness 5-6 mm as a result of the accumulation of secretions and the edema in the stroma. Progesterone inhibits the contractions of smooth muscle cells of the myometrium that might otherwise interfere with the implantation of the embryo.

Figure 8. Changes in the uterine glands and in the gland cells during the menstrual cycle. In the proliferative stage the glands are straight tubules, and their cells show no secretory activity.

5 Figure 8. Changes in the uterine glands and in the gland cells during the menstrual cycle. In the proliferative stage the glands are straight tubules, and their cells show no secretory activity. In the initial secretory phase the glands begin to coil, and their cells accumulate glycogen in the basal region. In the late secretory phase the glands are highly coiled, and their cells present secretary activity at their apical portion. The menstrual phase: When fertilization do not occur and the corpus luteum ceases functioning, the consequent rapid decrease of blood levels of progesterone and estrogen causes menstruation. Menstruation is the shedding of the endometrium which occurs due to several factors such as contraction and relaxation of spiral arteries, activation of metaloproteinases, and local release of prostaglandins, cytokines which lead to breakdown of blood vessel walls. Consequently, part of the functional layer of the endometium becomes detached. At the end of the menstrual phase, the endometrium is usually reduced to a thin layer of lamina propria, the blind ends of uterine glands (both of which present in the basalis layer), and some covering epithelium. Uterine cervix: The cervix is the lower, cylindrical part of the uterus. The lining consists of a mucous secreting simple columnar epithelium. The cervix has few smooth muscle fibers and dense connective tissue. The external aspect of the cervix that bulges into the lumen of the vagina is covered with stratified squamous epithelium. The mucosa of the cervix contains the mucous cervical glands that during pregnancy proliferate and secrete more viscous and abundant mucous. At the time of ovulation, the mucous secretions increased 10 times. It

6 becomes watery and allows penetration of the uterus by sperm. In luteal phase or in pregnancy, the progesterone levels alter the mucous secretions so that they become more viscous and prevent the passage of sperm, as well as microorganisms. The transformation zone is the site of abrupt transition between vaginal stratified squamous epithelium and cervical simple columnar epithelium. This area may undergo metaplastic changes which represent a precancerous lesion and may lead to CA cervix. The cervical epithelial cells are constantly exfoliated into the vagina. Stained preparations of the cervical cells (Papanicolaou [Pap] smears) are used routinely for screening and diagnosis of precancerous and cancerous lesions of the cervix. Transformation zone (arrow), CG-cervical gland Blockage of the openings of the mucosal glands results in the retention of their secretions, leading to formation of cyst within the cervix called Nabothian cysts which become important clinically only if numerous cysts make marked enlargement of the cervix. Vagina: The wall of the vagina consists of three layers: a mucosa, a muscular layer, and an adventitia. The epithelium of the vaginal mucosa of adult women is stratified squamous epithelium. Under the stimulus of estrogen, the vaginal epithelium synthesizes and accumulates a large quantity of glycogen which is deposited in the lumen of the vagina. Bacteria in the vagina metabolize glycogen and form lactic acid, which is responsible for the usually low ph of the

7 vagina. The acidic vaginal environment provides a protective action against some pathogenic microorganisms. The vaginal mucosa is virtually devoid of sensory nerve endings, and the few naked nerve endings that do exist are probably pain fibers. The muscular layer of the vagina is composed mainly of longitudinal bundles of smooth muscle fibers. There are some circular bundles. Outside the muscular layer is the adventitia which is rich in elastic fibers. The great elasticity of the vagina is related to the large number of elastic fibers in the connective tissues of its wall. External genitalia: The female external genitalia or vulva, consist of clitoris, labia minora, labia majora, and some glands that open into the vestibulum. The urethra and the ducts of the vestibular glands open into the vestibulum (space enclosed by the labia minora). The two glandulae vestibulares majores OR glands of Bartholin are situated on either side of the vestibulum. Numerous glandulae vestibulares minores are scattered. The clitoris and the penis are homologous in embryonic origin and histological structure. The labia minora are folds of skin with a core of spongy connective tissue permeated by elastic fibers. The labia majora are folds of skin that contain a large quantity of adipose tissue and a thin layer of smooth muscle. The external genitalia are abundantly supplied with sensory tactile nerve endings, including Meissner's and pacinian corpuscles, which contribute to the physiology of sexual arousal. Mammary glands: Each mammary gland consists of lobes, each lobe, separated from the others by dense connective tissue and much adipose tissue, is really gland in itself with its own excretory lactiferous duct. These ducts emerge independently in the nipple, which has openings. Breast development in puberty and in the adult: Breast enlargement during puberty is the result of the accumulation of adipose tissue and connective tissue, with increased growth and branching of the lactiferous ducts due to an increase in the amount of ovarian estrogens. The characteristic structure of the gland the lobe consists of several ducts that empty into one terminal duct. A denser connective tissue

8 separates the lobes. Near the opening of the nipple, the lactiferous ducts dilate to form the lactiferous sinuses. The lining of the lactiferous ducts and terminal ducts is formed of simple cuboidal epithelium covered by closely packed myoepithelial cells. The connective tissue surrounding the alveoli contains many lymphocytes and plasma cells, which increase significantly toward the end of pregnancy. It is responsible for the secretion of immunoglobulins (secretory IgA). The nipple has conical shape. It is covered by keratinized stratified epithelium. The skin around the nipple constitutes the areola. The color of the areola darkens during pregnancy, as a result of the local accumulation of melanin.the epithelium of the nipple rests on a layer of connective tissue rich in smooth muscle fibers. The nipple is abundantly supplied with sensory nerve endings. The breast during pregnancy and lactation: The mammary glands undergo intense growth during pregnancy. It occurs by the action of estrogen, progesterone, prolactin, and human placental lactogen, which cause proliferation of alveoli at the ends of the terminal ducts. Alveoli are spherical collections of epithelial cells that become the active milk secreting structures in lactation. Stellate myoepithelial cells are found between the alveolar epithelial cells and the basal lamina. The amount of connective tissue and adipose tissue decreases during pregnancy. Milk is produced by the epithelial cells of the alveoli and accumulated in their lumens and inside the lactiferous ducts. A few fat droplets and secretary vacuoles containing several milk proteins can be seen in the apical cytoplasm of the alveolar cells. The number of secretary vacuoles and fat droplets greatly increases in lactation. The sugar of milk is synthesized from glucose and galactose.

A: In nonpregnant women, the gland is quiescent and undifferentiated, and its duct system is inactive.

9 Figure 9. Schematic drawing of the female breast showing inactive and active mammary glands. Each lactiferous duct with its accompanying smaller ducts is a gland in itself and constitutes the lobes of the gland Figure 10. Changes in the mammary gland. A: In nonpregnant women, the gland is quiescent and undifferentiated, and its duct system is inactive. B: During pregnancy, alveoli proliferate at the ends of the ducts and prepare for the secretion of milk. C: During lactation, alveoli are fully differentiated, and milk secretion is abundant. Once lactation is completed, the gland reverts to the nonpregnant condition. In vitro fertilization (IVF) The selected women for IVF undergo hyperstimulation of the ovaries by gonadotropins and clomiphene with or without FSH to induce multiple follicle development and maturation. Mature pre-ovulatory oocytes are collected from Graaffian follicles by either laparoscope or ultrasound guided percutanous aspiration or trans-vaginal aspiration. These oocytes incubated in special medium. The collected semen is placed in special medium, then, the collected oocytes are added to the medium containing the collected semen hours later, the oocytes are examined to determine the presence of male and female pronuclei (the indication of successful fertilization). At this stage, the fertilized oocyte is transferred into special medium for hours to allow it to grow into the stage of 4-6 cells. After that, the

After transferring the embryos, intensive progesterone treatment is usually begun to mimic

10 embryos are transferred into the uterus which is already prepared by appropriate hormonal treatment to receive the embryos. After transferring the embryos, intensive progesterone treatment is usually begun to mimic the function of corpus luteum of pregnancy. A A: Human fertilized oocyte with male and female pronuclei. B: 48-hrs-old human embryo at 4 cells stage B

Female Reproductive System

Female Reproductive System (Part A-1) Module 10 -Chapter 12 Overview Female reproductive organs Ovaries Fallopian tubes Uterus and vagina Mammary glands Menstrual cycle Pregnancy Labor and childbirth Menopause