Female Reproductive System PDF

Female Reproductive System Dr. Lalit P. Singh Page 1 of 33 FEMALE REPRODUCTIVE SYSTEM Learning Objectives: 1. Describe the microanatomy and function of the ovary. Desc...

Female Reproductive System Dr. Lalit P. Singh Page 1 of 33 FEMALE REPRODUCTIVE SYSTEM Learning Objectives: 1. Describe the microanatomy and function of the ovary. Describe the histological organization of the ovary, beginning with its outermost layer of mesothelium. Describe the two major hormones produced by the ovary and their function. Describe the process of oogenesis. Describe the histological organization of a primordial follicle and its stage in the process of meiosis. Describe the histological organization of a primary follicle and its stage in the process of meiosis. Describe the physical relationship between granulosa cells and the oocyte. Describe the mechanism underlying meiotic arrest. Describe the histological organization of a secondary (antral) follicle and its stage in the process of meiosis. Describe the functional roles played by the theca interna and granulosa cells during oogenesis. Describe the functional role of the hypophysis in controlling the endocrine function of the ovary. Describe the histological organization of a Graafian (mature) follicle and its stage in the process of meiosis. Describe the change in endocrine secretions and in the meiotic process taking place in a Graafian follicle. Describe the process of ovulation. Describe the microanatomy and function of a corpus luteum. Describe the endocrine secretions and function of the corpus luteum. Describe the fate of the corpus luteum. Describe an atretic follicle. 2. Describe the microanatomy and function of the oviduct (uterine tube). Describe the histological organization of the oviduct and its role in reproduction. Describe the changes in the histology of the oviduct with the uterine cycle. Describe how the histological changes in the oviduct relate to ovarian function. 3. Describe the microanatomy and function of the uterus. Describe the histological organization of the uterine wall. Contrast the functions of the two layers of the uterine endometrium. Describe the blood supply of the uterine endometrium. Describe the sequence of histological changes the endometrium undergoes during the menstrual cycle and the cellular basis of the changes. Describe the hormonal control of the uterine endometrium. 4. Describe the microanatomy and function of the cervix. Describe the changes in the epithelium of the cervix going from uterus to vagina. Describe the glands found in the cervix and how their secretion changes during the menstrual cycle. Female Reproductive System Dr. Lalit P. Singh Page 2 of 33 5. Describe the microanatomy and function of the vagina. Describe the histological organization of the vagina. Compare and contrast the histological organization of the vaginal wall with the wall of the esophagus. 6. Describe the microanatomy and function of the mammary gland. Describe the histological organization of the inactive (nonpregnant) mammary gland. Describe the histological organization of the active (pregnant) mammary gland and contrast its organization with that of the inactive gland. Describe the histological organization of the lactating mammary gland and contrast its organization with that of the active gland. Describe the products released by the secretory alveolar cell and describe its mode(s) of secretion. Describe the role of hormones in the postnatal development of the mammary gland and in the control of lactation. Lecture Content Outline I. Ovaries II. Primordial follicles III. Primary follicles IV. Secondary (antral) follicles V. Graafian (mature) follicles VI. Corpus luteum VII. Atretic follicles VIII. Uterine tube (Oviduct) A. Function B. Regions C. Layers of wall IX. Uterus A. Function B. Regions C. Layers of wall D. Components of endometrium E. Layers of endometrium F. Endometrial blood vessels X. Uterine (endometrial, menstrual) cycle A. Description B. Three phases of cycle 1. Proliferative (follicular) stage 2. Secretory (luteal) phase 3. Menstrual (ischemic) phase XI. Cervix A. Description B. Endocervix C. Exocervix XII. Vagina XIII. Mammary gland A. Structure B. Inactive (nonpregnant) gland C. Active (pregnant) gland D. Lactating mammary gland Female Reproductive System Dr. Lalit P. Singh Page 3 of 33 Introduction The female reproductive system consists of internal sex organs and external genital structures. The internal female reproductive organs are the ovaries, uterine tubes, uterus, and vagina. I. OVARIES (Fig. 1) A. The two main functions of the ovaries are oogenesis (the production of gametes) and production of the steroid hormones estrogen and progesterone. Oogenesis Fig.1 is a type of gametogenesis and is the transformation of female germ cells (oogonia) into mature ova that can be fertilized by sperm. 1. Estrogen: Promotes growth and maturation of internal and external sex organs. Responsible for female sex characteristics. Acts on mammary glands to promote breast development. 2. Progesterone: Prepares the uterus for pregnancy by promoting changes in the endometrium. Prepares the mammary gland for lactation by promoting the proliferation of lobules. B. The ovaries are covered by a dense connective tissue capsule, the tunica albuginea, and a layer of mesothelium (cuboidal or almost squamous) (Fig. 2). Female Reproductive System Dr. Lalit P. Singh Page 4 of 33 C. The ovaries are organized with an outer cortex and inner medulla. The cortex is the outer portion of the ovary beneath the tunica albuginea. It consists of ovarian follicles and their derivatives embedded in stroma. The ovarian stroma is the connective tissue, and contains collagen fibers, ground substance, smooth muscle cells, and fibroblast-like cells. D. The medulla is the central core of the ovary. It consists of loose connective tissue containing blood vessels, lymphatic vessels, and nerves. There is no distinct boundary between the cortex and medulla. Fig. 2 E. Ovarian follicles and their derivatives found in the ovarian cortex are classified as: primordial follicles, primary follicles (unilaminar and multilaminar), secondary (antral) follicles, mature (Graffian follicles), corpus luteum, corpus albicans, and atretic follicles. II. PRIMORDIAL FOLLICLES (Fig. 3) A. Primordial follicles are the least developed of the ovarian follicles. Early primordial Fig. 3 follicle growth is independent of hormone stimulation. Follicles contain an oocyte that completes meiosis I and meiosis II. There are major differences between sperm and oocyte meiotic division. Female Reproductive System Dr. Lalit P. Singh Page 5 of 33 B. Primordial follicles consist of one oocyte (Fig. 4) that is arrested in Meiosis I (specifically the diplotene stage of prophase I). It is called a primary oocyte because it has not completed meiosis I. C. The primary oocyte is surrounded by a single layer of squamous cells called follicular cells. Note that Fig. 4 some textbooks and articles will call these granulosa cells. The follicular cells are surrounded by a basal lamina, and the basal lamina is surrounded by the connective tissue stroma of the ovarian cortex. The primary oocyte can remain arrested in meiosis I for 12-50 years (Fig. 5). III. PRIMARY FOLLICLES (Fig. 6) Fig. 5 A. Primordial follicles continue their development to become primary follicles. B. Primary follicles Fig. 6 contain a primary oocyte that continues to be arrested in meiosis I. The squamous follicular cells become cuboidal, and are now referred to as granulosa cells by all references. A unilaminar primary follicle refers to a follicle that is surrounded by one layer of cuboidal granulosa Female Reproductive System Dr. Lalit P. Singh Page 6 of 33 cells. The multilaminar primary Fig. 7 follicle is surrounded by many layers of granulosa cells (Fig. 7). C. The primary oocyte secretes a new layer between it and the granulosa cells called the zona pellucida. The zona pellucida is composed of four major glycoproteins (ZP1, ZP2, ZP3, ZP4 see Embryology lectures). The zona pellucida will stain pink/red with H/E and a magenta color with the PAS stain. D. At the TEM level, cortical granules appear throughout the ooplasm of a primary oocyte in a primary follicle (Fig. 8). Cortical granules contain proteases that are released if the oocyte is fertilized by sperm. The cortical reaction is one of the mechanisms used to block multiple Fig. 8 fertilization of the same oocyte (see Fertilization and Implantation lecture in Embryology Notes.) E. Processes from the granulosa cells closest to the zona pellucida extend through it and make contact with microvilli on the oocyte, establishing communication via gap junctions. This facilitates the transfer of metabolites from the granulosa cells to the oocyte. There are also extensive gap junctions between the granulosa cells. Female Reproductive System Dr. Lalit P. Singh Page 7 of 33 F. The connective tissue cells surrounding the basal lamina of the primary follicle become specialized into layers called the theca folliculi or just theca (Fig. 9). The innermost layer is called the theca interna. It is well vascularized and its cells will take on endocrine characteristics. The outer layer called the theca externa, is less well vascularized and blends in with the connective tissue stroma of the ovarian cortex. Theca development begins in the primary follicle but is best seen in secondary follicles. Fig. 9 IV. SECONDARY (ANTRAL) FOLLICLES A. The primary follicle will move deeper into the ovarian cortex and increase in size due mainly to proliferation of granulosa cells. Factors required for continued growth include follicle stimulating hormone (FSH), growth factors, and calcium. B. As the follicle continues to enlarge, a fluid-filled space, the antrum (Fig. 10), appears among the granulosa cells. The antrum Fig. 10 is a distinguishing feature of the secondary (antral) follicle. Female Reproductive System Dr. Lalit P. Singh Page 8 of 33 C. Secondary follicles contain one primary oocyte arrested in meiosis I, a zona pellucida, and an antrum. Secondary follicles are completely surrounded by the theca interna and theca externa D. The oocyte becomes eccentrically located in the follicle within a mound of granulosa cells now called the cumulus oophorus or cumulus mass (Figs. 11, 12). The oocyte will cease to grow due to the presence of oocyte maturation inhibitor (OMI) that is secreted by the granulosa cells into the antral fluid. Fig. 11 E. The cells of the cumulus oophorus that immediately surround the oocyte and remain with it at ovulation are referred to as the corona radiate (Fig. 12). F. The remainder of the granulosa cells lies in several layers along the basal lamina. G. The antrum is filled with liquor Fig. 12 folliculi composed mostly of hyaluronic acid but it contains hormones and growth factors as well (Fig. 13). Fig. 13 Female Reproductive System Dr. Lalit P. Singh Page 9 of 33 H. The theca interna and theca externa are prominent in secondary (antral) follicles. 1. The theca interna is the inner highly vascularized layer of steroid-secreting endocrine cells possessing receptors for luteinizing hormone (LH). In response to LH stimulation theca interna cells synthesize and secrete androgens (androstenedione) and some progesterone. The androgens pass through the basal lamina into the granulosa cells. 2. The theca externa, the outer layer of ovarian stromal cells, blends with the ovarian cortex. I. The granulosa cells, under the influence of FSH, convert the androgens (androstenedione) - received from the theca interna cells - into to estradiol, the main form of estrogen (Fig. 14). Estrogen stimulates granulosa cell proliferation which increases the size of the follicle. During the secondary follicle stage, the granulosa cells gradually acquire LH receptors in addition to their FSH receptors. Fig. 14 Female Reproductive System Dr. Lalit P. Singh Page 10 of 33 V. GRAAFIAN (MATURE) FOLLICLES (Fig. 15) A. Graafian or mature follicles are characterized by a large antrum, the zona pellucida, the detachment of the oocyte and corona radiata from the rest of the cumulus oophorus, and the completion of Meiosis I by the primary oocyte several hours before ovulation. They can reach 10 mm in diameter. B. In response to a surge of LH released from the anterior pituitary. Meiosis I of the primary Fig. 15 oocyte of the mature follicle resumes. C. 12-24 hours after the LH surge the secondary oocyte and first polar body are formed. The secondary oocyte is functional and contains 23 chromosomes each consisting of two chromatids. The secondary oocyte will proceed through Meiosis II until it reaches Metaphase II, then stops again (Fig. 16). This occurs just prior to ovulation. D. The first polar body also contains 23 chromosomes consisting of two chromatids. However the first polar body receives only a small amount of cytoplasm. While it may divide, it does not develop further, and will degenerate. E. Ovulation results in the release of one secondary oocyte, granulosa cells of the corona radiata, and granulosa cells of the cumulus mass from the ovary. All other elements of the mature follicle remain in the ovary. Female Reproductive System Dr. Lalit P. Singh Page 11 of 33 Fig. 16 F. As a step in the fertilization process, the membranes of the secondary oocyte and sperm fuse. It is not until then that the secondary oocyte completes meiosis II and is a true haploid cell. The completion of meiosis II results in the formation of an ovum and a second polar body. The second polar body is nonfunctional. The fertilized ovum (with male and female pronucleus) will develop into the embryo. Female Reproductive System Dr. Lalit P. Singh Page 12 of 33 VI. CORPUS LUTEUM A. After ovulation, the theca and granulosa cells remaining in the ovary collapse and become the corpus luteum (Fig. 17). B. The lumen of the corpus luteum, previously occupied by the antrum of the follicle, is replaced by a blood clot and Fig. 17 then by connective tissue (Fig.18). C. The granulosa cells transform into granulosa lutein cells, which are relatively large and eosinophilic. The theca interna cells of the follicle become theca lutein cells, which are relatively smaller, have less Fig. 18 cytoplasm, and so appear relatively more basophilic. Theca lutein cells form strands among the granulosa lutein cells. The granulosa cells and theca interna cells (both of which now have LH receptors) undergo "luteinization" (become cells filled with lipid) and mainly produce progesterone along with some estrogen. These hormones stimulate the growth and secretory activity of the endometrium to prepare it for implantation in the event of fertilization. Female Reproductive System Dr. Lalit P. Singh Page 13 of 33 D. If fertilization takes place, the corpus luteum continues to enlarge and produce progesterone and estrogen under stimulation of human chorionic gonadotropin (hCG) from the placenta. E. If fertilization does not occur, the corpus luteum regresses to a corpus albicans (Fig. 19). Connective tissue will eventually replace the degenerating luteal cells, producing an irregular, highly folded, glassy ("hyalinized"), eosinophilic form. The few cells that remain are mostly Fig. 19 macrophages. VII. ATRETIC FOLLICLES (Fig. 20) A. There are 600,000-800,000 primary oocytes present in a female at birth. However, only about 400 mature ova are produced during the reproductive lifespan. Many primary follicles begin development but usually only one follicle completes development per uterine cycle. The rest of the follicles degenerate in a process called atresia, and the degenerating follicles are called atretic follicles. Fig. 20 Changes associated with atretic follicles include: 1. Granulosa cell apoptosis 2. Invasion of the granulosa cell layer by neutrophils and macrophages Female Reproductive System Dr. Lalit P. Singh Page 14 of 33 3. Granulosa cells slough into the antrum 4. Theca interna cells hypertrophy 5. The follicle collapses as degeneration continues 6. Connective tissue invades into the follicle cavity B. Atretic primordial and small primary follicles cannot be detected histologically. When larger follicles degenerate, the basal lamina thickens, folds, and becomes eosinophilic and is often referred to as a "glassy membrane". A zona pellucida may also be recognizable in Fig. 21 atretic follicles (Fig. 21). C. Atretic follicles and corpus albicans differ in size with the corpus albicans being much larger and thicker. The presence of a zona pellucida helps identify an atretic follicle. VIII. UTERINE TUBE (OVIDUCT) A. The uterine tube (oviduct or Fallopian tube) receives the ovum following ovulation, provides the proper environment for fertilization, and transports it to the uterus Fig. 22 (Figure 22). Female Reproductive System Dr. Lalit P. Singh Page 15 of 33 B. Four regions of the uterine tube can be described (Fig. 22): 1. The infundibulum is a funnel-shaped segment adjacent to the ovary. Fimbriae extend from the infundibulum toward the ovary. At the time of ovulation the fimbriae move close to the surface of the ovary and direct the oocyte into the uterine tube. 2. The ampulla is the longest segment of the uterine tube. This is typically where fertilization takes place. 3. The isthmus is the narrow region of the uterine tube near the uterine wall. 4. The intramural segment (uterine part) opens into the cavity of the uterus. C. The wall of the uterine tube is composed of mucosa, muscularis, and serosa (Fig. 23): Fig. 23 1. The mucosa consists of simple columnar epithelium with ciliated columnar cells and nonciliated secretory cells (peg cells) and underlying lamina propria (Fig. 24). a. Mucosal folds project into the lumen of the oviduct. There are more folds in the ampulla (Fig. 25) compared Fig. 24 to the isthmus or intramural segment (Fig. 26). Female Reproductive System Dr. Lalit P. Singh Page 16 of 33 b. The epithelial cells undergo cyclic hypertrophy during the follicular phase and atrophy during the luteal phase of the uterine cycle in response to changes in hormone Fig. 25 levels, mainly estrogen. c. During the uterine cycle estrogen simulates ciliogenesis and progesterone increases the number of secretory (peg) cells. Fig. 26 d. At about the time of ovulation the epithelium reaches its maximum height. This is reduced to about one-half just before menstruation (Fig. 27). e. Peg cells produce fluid containing nutrients for both spermatozoa and ova. Fig. Fig. 27 Fig. Female Reproductive System Dr. Lalit P. Singh Page 17 of 33 2. The muscularis of the uterine tube consists of an inner circular and outer longitudinal layer of smooth muscle. The beating of the cilia toward the uterus coupled with the peristaltic contractions of the muscularis function in movement of ovum toward the uterus. 3. The serosa is the peritoneal covering of the uterine tube. Glands are not found in the oviduct. IX. UTERUS (Fig. 22, reproduced at right) A. The uterus is a hollow pear- shaped muscular organ that provides an attachment site for the developing embryo. Fig. 22 B. Regions of the uterus: 1. The body is the expanded upper region of the uterus; it constitutes the bulk of the organ. 2. The fundus is the rounded part of the uterus where the oviducts join. The body and fundus have a similar histological organization. 3. The cervix is the lower part of the uterus, part of which protrudes into the upper vagina. Female Reproductive System Dr. Lalit P. Singh Page 18 of 33 C. The wall of the body and fundus of the uterus is composed of three layers: endometrium, myometrium and perimetrium (Fig. 28): 1. Endometrium is the mucosa of the uterus, with epithelium and underlying connective tissue. 2. The myometrium (analogous to a muscularis) is the thickest layer of the uterine wall and consists of three layers of smooth muscle in indistinct layers. The larger blood vessels of the uterus are found mostly in the middle layer of smooth muscle (stratum vasculare). Fig. 28 During pregnancy the myometrium undergoes both hypertrophy (increase in cell size) and hyperplasia (increase in cell number). Uterine smooth muscle atrophies in the absence of estrogen (e.g., at menopause). 3. The perimetrium is the outer layer of the uterus. D. Components of the endometrium (Fig. 29): 1. The surface of the uterus has simple columnar epithelium containing ciliated cells and secretory cells. Fig. 29 Female Reproductive System Dr. Lalit P. Singh Page 19 of 33 2. Uterine glands are lined with a simple columnar epithelium of secretory cells and ciliated cells. The glands are classified as simple tubular or simple branched tubular. The deepest parts of the glands may reach almost to the myometrium. 3. The cellular collagenous connective tissue surrounding the glands in the endometrium is called the stroma. E. Two layers can be described in the endometrium that differs in structure and function (Fig. 30): 1. The functional layer (stratum functionale or stratum functionalis) is the upper thick layer of the endometrium. Fig. 30 a. This layer undergoes changes in the appearance and function of the uterine glands, endometrial stroma, and blood vessels during the uterine cycle. b. This layer is sloughed off (lost) during menstruation. 2. The basal layer (stratum basale, stratum basalis, lamina basalis) is the layer of endometrium adjacent to the myometrium. a. The structure and function of the basal layer do not change to any great extent during the uterine cycle. Female Reproductive System Dr. Lalit P. Singh Page 20 of 33 b. It is not shed at menstruation, but remains to regenerate the functional layer. F. The blood vessels of the endometrium undergo cyclic changes. 1. The uterine artery branches into arcuate arteries that supply the endometrium. The arcuate arteries course circumferentially within the myometrium and directly or indirectly produce two arteries (Fig. 31): a. Straight arteries supply the basal layer of the endometrium. b. Spiral (helical) arteries supply the functional layer. 2. The spiral arteries give off arterioles that supply capillary beds 3. The straight arteries change little during the uterine cycle. Spiral arteries in the Fig. 31 functional layer degenerate and regenerate with each uterine cycle. X. UTERINE (ENDOMETRIAL, MENSTRUAL) CYCLE A. Throughout the reproductive lifespan of a female the endometrium of the uterus undergoes cycles of proliferation, secretion, necrosis and shedding. This is known as the uterine cycle or the menstrual cycle. The cycle involves changes in the structure and secretory activity of uterine epithelium, glands, stroma, and blood vessels. The Female Reproductive System Dr. Lalit P. Singh Page 21 of 33 stages of the uterine cycle correlate to the activity and hormonal production of the ovaries (Fig. 32). Fig. 32 B. The uterine cycle can be divided into three phases that blend one into the other: 1. PROLIFERATIVE (FOLLICULAR) PHASE: This phase occurs concurrently with the growth and maturation of ovarian follicles and their secretion of estrogen. During the proliferative phase the functional layer is being rebuilt by mitotic divisions of cells in the basal layer (Fig. 33). Fig. 33 a. Epithelial cells in the basal layer undergo mitosis to reconstitute uterine glands and to resurface the endometrium. Female Reproductiv R ve System Dr. Lalitt P. Singh Page 22 of 33 b. Hisstologically,, the uterine glands appeear straight w with a narrow n lumen n (Fig. 33). c. Th he number off endometriaal stromal ceells increasess by mittosis and thee amount of ground subsstance inccreases. d. Th he spiral segm ments of arcuuate arteriess extend throough thee upper 2/3 of o the endom metrium. 2. SECRETO ORY (LUTEAL) PHA ASE: This phhase coincidees with activiity of the corrpus luteum in the ovaryy and its secretion of o progestero one. a. Hisstologically the uteerine glands enllarge and tak ke on a corkscrew w shaape (Fig. 34)) beccause they beccome filled with w gly ycogen and Fig. 34 gly ycoproteins produced p byy the secretorry cells. b. Th he endometrial stroma beecomes edem matous. Towards the en nd of the seccretory phasee, the stromaal cellls enlarge du ue to accumu mulation of gllycogen. Thhe inffluence of esstrogen and pprogesteronee on these ceells ren nders them capable c of di fferentiatingg into deciduual cellls. In the event that an im mplantation occurs, thesse cellls will form the deciduaa basalis. Female Reproductive System Dr. Lalit P. Singh Page 23 of 33 c. The spiral arteries become more coiled and extend nearly to the uterine surface. 3. MENSTRUAL (ISCHEMIC) PHASE (Fig. 35): Called ischemic phase in Fertilization and Implantation notes. This phase coincides with the degeneration of the corpus luteum in the ovary, and a decrease in estrogen and progesterone levels. a. The epithelial cells of the uterine glands stop secreting glycogen. b. There is a loss of fluid in the stroma and the stromal Fig. 35 cells become more densely packed. c. Periodic contractions of the walls of the spiral artery segments cause the functional layer to become ischemic. Eventually the spiral arteries close off, shutting off blood flow to the functional layer. Blood continues to flow to the basal layer. d. Continued interruptions in blood flow result in the sloughing of stromal and epithelial cells, blood and uterine fluid (menstruation). Clinical Correlations: Endometriosis - The presence of endometrial tissue in the pelvis or in the peritoneal cavity is known as endometriosis. It has been shown that the extrauterine endometrial tissues can undergo cyclic changes similar to the endometrium associated with the uterus. Hemorrhaging of the extrauterine tissue may cause adhesions and pain. If not corrected, the pelvic viscera may become associated with a fibrotic mass, and sterility may result. Female Reproductive System Dr. Lalit P. Singh Page 24 of 33 XI. CERVIX A. The cervix is the narrow or constricted region of the uterus, part of which projects into the vagina. B. Endocervix: The endocervical canal runs between the uterine and vaginal cavities (Fig. 36). Fig. 36 1. The epithelium lining the endocervix is simple columnar and consists mainly of mucus-secreting cells with some ciliated cells. 2. Cervical glands are deep branched invaginations of the surface epithelium. This creates a large surface area for secretion (Fig. 37). Fig. 37 a. The endocervix does not undergo any histological changes during the uterine cycle. b. The secretory activity of cells in endocervical glands is regulated by estrogen. During ovulation the mucus is relatively less viscous (thinner) and has an alkaline pH. These are conditions favorable for sperm Female Reproductiv R ve System Dr. Lalitt P. Singh Page 25 of 33 migration. Afteer ovulation the mucus bbecomes moore visscous (thickeer) and has aan acidic pH.. These con nditions are harmful to ssperm. 3. The ducts of cervical glands g may becom me occluded d with secretions,, forming Nabothian n cysts (Fig. 38). C. C Exoceervix: The ex xternal surfaace of the paart of the cerv vix that prottrudes into th he vagina is called the exocervix (Fig. 39 9). F Fig. 38 1. The simplee columnar epithelium e oof the endoceervix changees abruptly to o the stratifieed squamouss epithelium m of the exocervix.. The stratiffied squamouus epithelium m is typicallyy non-keratiinized and iss continuous with the epiithelium of tthe vagina. Fig. 39 Female Reproductive System Dr. Lalit P. Singh Page 26 of 33 Clinical Correlations: The papanicolaou or “Pap smear” - is a diagnostic tool for detection of cervical cancer. It is performed by aspirating cervical fluid from the vagina or by taking scrapings directly from the cervix. The tissue or fluid is prepared and stained on a microscope slide, then examined for variations in the cell population to detect carcinoma. Cervical carcinoma is one of the most common cancers in women. It develops from the stratified squamous nonkeratinized epithelium of the cervix, where it is called "carcinoma in situ". If detected by a Pap smear in this stage, it can usually be treated with surgery. If not detected early, it may invade other areas and metastasize, thus changing to invasive carcinoma, which has a poor prognosis. XII. VAGINA A. The vagina consists of a mucosa, muscularis, and adventitia. B. The mucosa consists of non- keratinized stratified squamous epithelium with underlying lamina propria Fig. 40). The superficial cells Fig. 40 of this epithelium may store glycogen. The greatest accumulation of glycogen occurs at the time of ovulation, thus these cells may appear large and clear at that time. C. There are no glands or muscularis mucosae as part of the vaginal mucosa (Fig. 41). Fig. 41 Female Reproductive System Dr. Lalit P. Singh Page 27 of 33 D. The muscularis contains ill-defined bundles of circularly arranged smooth muscle and a more prominent outer layer of longitudinally arranged smooth muscle. E. The adventitia is composed of collagenous tissue containing elastic fibers, large blood vessels and nerves. XIII. MAMMARY GLAND (Fig. 42) A. The mammary glands develop from epidermis and are classified as compound tubuloalveolar, modified apocrine sweat glands. 1. Mammary glands consist of 15-25 lobes containing a variable number of lobules. Each lobe radiates from the nipple and empties on to the Fig. 42 surface of the nipple through a lactiferous sinus and duct. 2. The lobes and lobules in the mammary gland can be identified based on the type of connective tissue. The intralobular connective tissue (connective tissue within the lobule) is loose connective tissue. The interlobular connective tissue (connective tissue between lobules) is dense irregular. Female Reproductive System Dr. Lalit P. Singh Page 28 of 33 B. INACTIVE (nonpregnant) GLAND 1. In an inactive mammary gland the lobules mainly contain ducts in addition to loose connective tissue (Fig. 43). The ducts are lined with simple cuboidal epithelium. Myoepithelial cells are present between Fig. 43 the epithelium and basal lamina. 2. The inactive breast (Fig. 44) will undergo minor changes associated with the uterine cycle under the influence of estrogen. Some proliferation of the ducts may occur as well as transient edema. Fig. 44 C. MAMMARY GLAND DURING PREGNANCY - THE PROLIFERATIVE GLAND (Fig. 45) 1. The mammary gland exhibits many changes during pregnancy in preparation for Fig. 45 lactation: Female Reproductive System Dr. Lalit P. Singh Page 29 of 33 a. The epithelium of the intralobular ducts proliferates and differentiates into milk-secreting cells, forming secretory alveoli within the lobules. Both the secretory alveoli and the intralobular ducts are lined with simple cuboidal epithelium. Estrogen stimulates the proliferation of the ducts. Progesterone stimulates growth of the secretory alveoli. b. Adipose tissue and connective tissue decreases because of the growth of the secretory alveoli (Fig. 46). Enlargement of the breast is due to proliferation of the Fig. 46 ductal and alveolar cells, hypertrophy of the secretory cells, and accumulation of secretions in the alveoli. c. Plasma cells, lymphocytes and eosinophils infiltrate the connective tissue. D. LACTATING MAMMARY GLAND (Fig. 47) 1. The major histological difference between the proliferative and lactating gland is that the lumens of the secretory alveoli dilate due to the accumulation of milk. Fig. 47 Female Reproductive System Dr. Lalit P. Singh Page 30 of 33 a. The alveoli and intralobular ducts of lactating mammary glands are made up of cuboidal epithelium and myoepithelial cells (Fig. 48). b. Only a small amount of connective tissue Fig. 48 separates the alveoli. 2. Milk production (Fig. 49) a. The secretory cells of the alveoli are characterized by the presence of lipid droplets and milk protein-containing secretory vesicles (Figs. 49, 50, 51). b. Milk proteins are released by merocrine secretion. Fig. 49 c. Individual lipid droplets coalesce and pass to the apical region of the cell. They are released with some plasma membrane and cytoplasm. Therefore, the lipid component of milk is released by apocrine secretion. Female Reproductive System Dr. Lalit P. Singh Page 31 of 33 Fig. 50 Fig. 51 3. Secretions released by the alveoli in the first few days (2-3) after childbirth is called first milk or colostrum. a. This milk contains more protein and fewer lipids than actual milk. b. Secretory IgA and IgG produced by plasma cells is found in colostrum. These antibodies confer passive immunity to the newborn. 4. During pregnancy placental estrogen and progesterone suppress the release of prolactin from the adenohypophysis. After birth, prolactin release stimulates the production of lipid-rich milk. 5. Suckling stimulation of the breast by the baby results in a neural-humoral reflex to release milk. Neural sensory impulses from the breast ultimately impinge on the supraoptic and paraventricular nuclei of the hypothalamus. Oxytocin released from the neurohypophysis stimulates myoepithelial cell contraction of the alveoli and lactiferous ducts, leading to the ejection of milk. Female Reproductive System Dr. Lalit P. Singh Page 32 of 33 E. The mammary gland atrophies or involutes after menopause. Summary of Stages in Mammary Gland Development (Fig. 52) Inactive Proliferative Lactating Fig. 52 Clinical Correlations: Breast cancer - one of the major cancers in women may be of two different types. Ductal carcinoma involves the ductal cells, while lobular carcinoma involves the terminal ductules. Detection must be early or prognosis is poor because the cancer may metastasize to the axillary lymph nodes and from there to the lungs, bone and brain. Female Reproductive System Dr. Lalit P. Singh Page 33 of 33 References: Ross, M. R., Kaye, G.I., Pawlina, W. Histology 4th Ed., Baltimore: Lippincott, Williams & Wilkins, 2003, Chap. 22, "Female reproductive system". Pawlina G. I., Ross M. R. Histology with Correlated Cell and Molecular Biology, 7th Edition, 2015, Chapter 23, Female Reproductive System. Kerszenbaum, A.L. Histology and Cell Biology, St. Louis, Mosby, 2002, Chap. 22. MacCallum, D.K. Michigan Medical Histology, University of Michigan, Ann Arbor, 2000. Chapter: Female reproductive system Gartner, L.P., Hiatt, J. L. Color Atlas of Histology, 3rd Ed., Lippincott, Williams & Wilkins, Philadelphia, 2000, Chap. 17. Meyer, D.L., Unpublished histology slide atlas, Department of Anatomy, Wayne State University School of Medicine, 1970. Erlandsen, S.L., Magney, J. E., Human Histology, University of Minnesota Press, 1985, "Female Reproductive System". Rhodin, J. A. G, Histology, Oxford University Press, 1974, Chap. 34. 12/05/2022