Female Reproductive System - Lecture Notes PDF

Female reproductive system Prof. Zbigniew Kmiec, MD, PhD Schematic drawing of posterior view of female internal sex organs. PPPart of the wall of the uterus, uterine tube, and vagina has been removed to reveal their internal structure. Pawlina, Ross, 2020 There are three distinct layers of t...

Female reproductive system Prof. Zbigniew Kmiec, MD, PhD Schematic drawing of posterior view of female internal sex organs. PPPart of the wall of the uterus, uterine tube, and vagina has been removed to reveal their internal structure. Pawlina, Ross, 2020 There are three distinct layers of the uterine wall: the inner layer, the endometrium lining the uterine cavity; the middle and thickest layer, the myometrium; and the outer layer, the perimetrium, which is the peritoneal covering of the uterus.  Ovaries are almond- shaped bodies approximately 3-cm long, 1.5-cm wide, and 1-cm thick. Each ovary is covered by a simple cuboidal epithelium, the surface (or germinal) epithelium and overlying a layer of dense connective tissue capsule, the tunica albuginea. Basic Histology, text & atlas, L.C.Junqueira, 2010. The ovary consists of: the cortex, a region with a stroma of highly cellular connective tissue and many ovarian follicles the medulla, containing loose connective tissue and blood vessels. There is no distinct border between the ovarian cortex and the medulla.  The two major functions of the ovary are production of gametes and steroid hormones (estrogens and progesterone) Estrogens promote the growth and maturation of internal and external sex organs and are responsible for the female sex characteristics that develop at puberty. Estrogens also act on mammary glands to promote breast development by stimulating ductal and stromal growth and accumulation of adipose tissue. Pawlina, Ross, 2020 Progesterone prepares the uterus for pregnancy by promoting secretory changes in the endometrium and also prepares the mammary gland for lactation by promoting lobular proliferation. This drawing shows stages of follicular development from the early primary follicle to the mature (Graafian) follicle. The maturation of the follicles occurs in the direction of the arrow. Changes in the follicle after ovulation lead to development of the corpus luteum and eventually the corpus albicans. Highly coiled blood vessels are present in the hilum and medulla of the ovary.  OOGENESIS and OVARIAN FOLLICLES PRIMORDIAL FOLLICLES - contain primary oocyte surrounded by an outer layer of flat follicular or granulosa cells Primordial follicles are generated at fetal life, and they are retained in resting phase for 13-50 years! Each egg BEGINS OOGENESIS IN FETAL LIFE as a PRIMARY OOCYTE, however, its 1st meiotic division is blocked at prophase by OMI (oocyte- maturation inhibitor secreted by follicular cells) Developing egg = SECONDARY OOCYTE is released during ovulation each month from puberty (menarche) until menopause - a total of 400-500 eggs/ life Pawlina, Ross, 2020 THE RELATIONSHIP BETWEEN THE MENSTRUATION CYCLE AND THE OVARIAN CYCLE: OVARIAN CYCLE : Ovarian cycle is accompanied by endometrial cycle These cyclic phases: - are interrupted only by pregnancy - continue from menarche until menopause, when reproductive capability ends. The ovarian cycle lasts usually 28 days. It is accompanied by cyclic changes of the mucosa of the uterus (endometrium) in the order of menstrual, proliferative and secretory phases. OVARIAN CYCLE is initiated by increase of blood FSH level. FSH is secreted by basophil cells of the adenohypophysis which are stimulated by GnRH released by hypothalamic neurons. FSH stimulates release of estrogens into blood from granular cells of ovarian follicles and lutein cells of corpus luteum. OVULATORY PHASE: release of a secondary oocyte from the Graafian 2 (mature) follicule. 1 OVULATION is caused by high increase of blood LH level. LH is secreted by basophil cells of the adeno- hypophysis which are stimulated by hypothalamic GnRH. FSH - follicle stimulating hormone LH - luteinizing hormone LUTEAL = SECRETORY PHASE is dominated by CORPUS LUTEUM (yellow body), which secretes progesterone, estrogens and other hormones  OVARY: - production & release of female gamets → ova = eggs (400,000 potential eggs are present at birth) - Secretion of female sex hormones: Estradiol (plus estron & estriol) and Progesterone Production of other hormones: Ovarian germ cell number is -Relaxin, produced by both maximal at mid-gestation and the ovary and the placenta; decreases precipitously thereafter. -induces relaxation of the pelvic ligaments and softens cervix to facilitate childbirth. Oxytocin (increases - contractions of uterus during parturition) Inhibin (secreted by Graafian follicle), blocks FSH secretion. Through the combined processes of mitosis, meiosis, and atresia, the population of oogonia reaches its maximum of 6–7 million by 20 weeks of gestation, after which there is a progressive loss of both oogonia and primordial follicles through the process of atresia. It appears that entry into meiosis provides some degree of protection from programmed cell death. At birth, oogonia are no longer present in the ovary, and only 1–2 million germ cells remain in the form of primordial follicles The surface of the ovary is covered by so called GERMINAL EPITHELIUM, a single layer mainly cuboidal cells. It is continuous with mesothelium that covers the mesovarium. The term germinal epithelium is a carryover from the past when it was incorrectly thought to be the site of germ cell formation during embryonic development. However, we now know that the primordial germ cells are of extragonadal origin since they migrate from the embryonic yolk sac into the cortex of the embryonic gonad, where they differentiate and induce differentiation of the ovary. A dense connective tissue layer, the tunica albuginea, lies between the germinal epithelium and the underlying cortex. Tumors that arise from the epithelial surface of the ovary account for more than 70% of OVARIAN CANCERS. The origin of surface epithelial tumors may be related to repeated disruption and repair of the germinal epithelium that occurs during ovulation.  PRIMORDIAL FOLLICLES - OOGENESIS and contain primary oocyte OVARIAN FOLLICLES surrounded by an outer layer of flat follicular or granulosa cells. Primordial follicles are generated at fetal life, and they are retained in resting phase for 13-50 years! Each egg BEGINS OOGENESIS IN FETAL LIFE as a PRIMARY OOCYTE, however, its 1st meiotic division is blocked at prophase by OMI (oocyte- maturation inhibitor secreted by follicular cells) Developing egg = SECONDARY OOCYTE is released during ovulation each month from puberty (menarche) until menopause - a total of 400-500 eggs/ life Gartner, 2018  Structure of primordial (non-growing) follicles (F) - primary oocyte (25-30 mm) - nucleoplasm contains uncoiled chromosomes - Abundant organelles with few ribosomes - Balbiani body - Annulate lamellae - Cortical granules - single layer of squamous follicular cells connected by desmosomes and supported multicellular stroma of the ovarian CORTEX by basal lamina Early growth of primordial follicles does NOT depend on FSH  Pawlina, Ross, 2020 At the ultrastructural level, the Balbiani body is a localized accumulation of Golgi membranes and vesicles, endoplasmic reticulum, centrioles, numerous mitochondria, and lysosomes. Human oocytes contain annulate lamellae which resemble a stack of nuclear envelope profiles. Each layer of the stack includes pore structures that are morphologically identical to nuclear pores. Moreover, numerous small vesicles are scattered throughout the cytoplasm along with small, spherical mitochondria. Follicules leaving the resting state are called PRIMARY F. At least one layer of CUBOIDAL follicular cells identifies the primary F (unilaminar primary follicle). Multilaminar primary follicules are shown below. The oocyte is ca. 100 mm big. Following processes occur during maturation of the oocyte in primary follicle: single Balbiani body of the primordial oocyte transforms into multiple, dispersed Golgi elements. The number of free ribosomes, mitochondria, small vesicles, and multivesicular bodies and the amount of RER increase. Occasional lipid droplets and lipochrome pigment masses may also be seen. The oocyte exhibits specialized secretory vesicles, cortical granules just beneath the oolemma which contain proteases released during cortical reaction when sperm cell reacts with zona pellucida proteins (block against polyspermia). Pawlina, Ross, 2020 Numerous irregular microvilli project from the oocyte into the perivitelline space between the oocyte and the surrounding granulosa cells as the zona pellucida is deposited. At the same time, slender The follicular phase begins with the development of 6 to 12 primary processes (filopodia) from follicles. This development is NOT granulosa cells develop and FSH-dependent. By the 6th day of project toward the oocyte, the cycle, one follicle predominates and the others become atretic (= intermingling with oocyte degenerate = gradually disappear). microvilli. Pawlina, Ross, 2020  Primary follicle: 2 morphological stages Multilaminar = multilayered Unilaminar=unilayered 1. Primary oocyte 2. Zona pellucida contains 4 1. Primary oocyte glycoproteins: ZP-1, -2, -3, -4 2. Zona pellucida 3. Proliferation of follicular cells make formation by oocyte granulosa cell layer - connexin 43 in gap junctions 3. Single layer of 4. Connexin 37 between oolema and cuboidal follicular granulosa cells cells 5. Basal lamina 4. Basal lamina 6. Theca interna – inner cellular layer separates follicule richly vascularized from the CT stroma 7. Theca externa – outer fibrous layer of stromal CT with myocytes  SEM of primary follicle and ZP is composed of glycoproteins that bind to the capacitated spermatozoa and induce zona pellucida (ZP) acrosomeal reaction. ZP-3 and ZP-4 function as the primary spermatozoa-binding receptors present in acrosomal cap. ZP-1 and ZP-2 act as secondary spermatozoa-binding proteins that interact mainly with the equatorial segment of the spermatozoon head. In addition, ZP-1, ZP-3, and ZP-4 are responsible for the induction of the acrosomal reaction in capacitated spermatozoa. Subsequent to the fusion of the spermatozoon membrane with the plasma membrane of the Basic Histology, 12th ed. oocyte (oolemma), ZP glycoproteins are An SEM of a fractured primary follicle shows the cleaved by metalloproteases, which are oocyte surrounded by granulosa cells (GC). released from cortical granules, thus making Between the very large oocyte surface and the granulosa cells is a fibrous layer of extracellular ZP proteins nonrecognizable for binding with material, the zona pellucida (ZP), which contains other spermatozoa. four related glycoproteins that bind sperm and form an irregular meshwork. PCOS – POLYCYSTIC OVARY SYNDROME = INFERTILITY A section through the cortex of the ovary from a woman with polycystic ovary disease. The unusually thick tunica albuginea (TA) that overlies numerous follicles prevents ovulation of the mature (Graafian) follicles. One of the follicles has developed to the primary follicle stage. ×45. Pawlina, Ross, 2020 Pawlina, Ross, 2020  Secondary = antral follicule: proliferation of granulosa cells and antrum formation are dependent on FSH, growth factors (EGF, IGF-1), activin, estrogens and Ca++ 1. Primary oocyte enlarges to 125 mm: its microvilli extend into zona pellucida and contact filipodia of granulosa cells via gap junctions 2. Zona pellucida becomes thicker 3. Granulosa layer ◼ Fluid begins to accumulate between granulosa cells (when 6-12 cell layers are present) ◼ Fluid-filled spaces coalesce to form a single large cavity → ANTRUM that gradually enlarges ◼ Narrow granulosa cell processes extend into zona pellucida 4. BASAL LAMINA, ◼ Cells contact each other and 5. Theca interna, oolema via gap junctions 6.Theca externa SECONDARY FOLLICLE contains fluid-filled antrum (A), which arises by the coalescence of small fluid-filled cavities among the granulosa cells. The circle-shaped enlargement depicts the relationship of the granulosa cells (GC), basal lamina, and the theca interna (TI) and theca externa (TE). The cells of theca interna differentiate into highly vascularized, steroid-producing cells. The theca interna is surrounded by an outer layer of stromal cells called the theca externa. The basal lamina separates granulosa cells from theca interna. Pawlina, 2020 Pawlina, Ross, 2020  Illustration and photograph of large secondory but yet NOT Graafian follicle Large antrum contains an oocyte embedded within the cumulus oophorus (CO).The cells of the cumulus oophorus immediately surrounding the oocyte remain with it after ovulation and are referred to as the corona radiata. The cells that surround the lumen of the antrum (A) make up the membrana granulosa (stratum granulosum, SG) of the follicle’s wall. TI, theca interna Pawlina, Ross, 2020  CORONA RADIATA: one layer of granulosa cells attached to zona pellucida, covers oocyte. Larger antral follicules have oocyte located on a ZG, stratum granulosum side (excentrically) at the cumulus oophorus, a small hill formed by Cumulus proliferating granulosa cells granulosa cells Mural granulosa cells (membrana granulosa) Functional Histology 2004  Liquor folliculi is rich in Secondary hyaluronic acid and = antral proteoglycans, steroid- follicle binding proteins, estrogens, progesterone, inhibin, activin (secreted by oocyte), follistatin, FOLLISTATIN is an extracellular FSH, antagonist growth factors. of activin OMI (oocyte maturation inhibitor) secreted by granulosa cells inhibits oocyte’s growth. Functional Histology, 2004 The synthesis of estrogens in the ovary requires a synergistic communication between theca interna and granulosa cells Kierszenbaum, 3rd ed.  Paracrine and autocrine interactions between theca cells, granulosa cells, and the oocyte Not obligatory slide Reproductive Endo- crinology, 2019 A , Androstenedione; BMP, bone morphogenetic protein; E , estradiol; FGF , fibroblast growth factor; FSH , follicle-stimulating hormone; GDF , growth differentiation factor; HGF , hepatocyte growth factor; IGFs , insulin-like growth factors; KGF , keratinocyte-derived growth factor; KL , c-kit ligand = stem cel factor; LH , luteinizing hormone; TGF , transforming growth factor. (Modified from Nillson E, Skinner MK: Cellular interactions that control primordial follicle development and folliculogenesis. J Soc Gynecol Investig 8[Suppl 1]:S17–S20, 2001.) Mature = Graafian follicule is very large, up to 20-25 mm. Few hours before ovulation the 1st meiotic division is completed resulting in the formation of a SECONDARY OOCYTE and 1st polar body. ◼ FSH INDUCES follicular cells to acquire luteinizing hormone (LH) receptors what is critical for ovulation. ◼ Blood level of estrogens produced by the follicule is very high (estrogens and INHIBIN block FSH secretion and development of other nondominant Graafian follicles). A. Stevens, J. Lowe. Histology,1994 Arrow indicates stigma in the place where mature follicle will ovulate (laparoscopy) Cell Journal, Spike Walker  a. A VIEW OF THE HUMAN OVARY DURING ENDOSCOPIC OOCYTE HARVEST SURGERY. The ovary is in the stage just before ovulation. Note the area of the bulging follicle with the follicular stigma clearly visible. The germinal epithelium covering the tunica albuginea is ruptured in the area of imminent ovulation. b. Ultrasound imaging helps in monitoring of follicular growth and is useful as a method for determining the time for harvesting preovulatory oocytes. Pawlina, Ross, 2020 Mechanics of ovulation Kierszenbaum & Tres, 2017 = Stem cells Fibrin clot is penetrated by newly formed blood vessels, fibroblasts and collagen fibers. A connective tissue network is formed. TRANSFORMATION OF THECA INTERNA AND FOLLICULAR CELLS: cells triple in size and start accumulate LUTEIN, a yellow pigment, within few hours after ovulation.  Ovulation is the process by which a secondary oocyte is released from Graafian follicle passing entire follicular wall and germinal epithelium A combination of hormonal changes and enzymatic effects is responsible for the actual release of the secondary oocyte, which occurs 14 days before the start of the next menstrual cycle. These factors include: ◼ increase in the volume and pressure of the follicular fluid; ◼ enzymatic proteolysis of the follicular wall by activated plasminogen; ◼ hormonally directed deposition of glycosaminoglycans between the oocyte–cumulus complex and the stratum granulosum; and ◼ contraction of smooth muscle fibers in the theca externa layer, triggered by prostaglandins. ◼ Just before ovulation, blood flow stops in a small area of the ovarian surface overlying the bulging follicle called follicular stigma which becomes elevated and then ruptures. ◼ The oocyte, surrounded by the corona radiata and cumulus oophorus cells is released from the ruptured follicle. ◼ At the time of ovulation, the fimbriae of the uterine tube become closely apposed to the surface of the ovary, and the cumulus mass containing the oocyte is gently swept by the fimbriae into the abdominal ostium of the uterine tube. ◼ The cumulus mass firmly adheres to the fimbriae and is transported by the ciliated cells lining the uterine tube, preventing its passage into the peritoneal cavity.  Corpus luteum After ovulation, the granulosa cells and theca interna of the ovulated follicle reorganize to form a larger temporary endocrine gland, the corpus luteum (L., yellowish body), in the ovarian cortex. Ovulation is followed immediately by the collapse and folding of the granulosa and thecal layers of the follicle’s wall, and blood from disrupted capillaries typically accumulates as a clot in the former antrum forming corpus hemorrhagicum granulosa cells granulosa lutein cells located centrally in the corpus luteum and constitute about 80% cells secrete progesterone and estrogens theca interna theca lutein cells located peripherally in the corpus luteum and constitute about 20% cells secrete progesterone and androstenedione (androgens)  Corpus luteum is a temporary endocrine gland. 1. GRANULOSA LUTEIN cells secrete progesterone (produced from cholesterol) AND estrogens (produced from androstendione) in response to both FSH and LH. 2. THECA LUTEIN cells secrete androstenedione and progesterone in response to LH. Stevens, Lowe. Histology, 1994 Granulosa lutein cells still lack the steroidogenic enzyme required for the complete synthesis of estradiol. Yet, they can synthesize progesterone. Theca lutein cells cooperate with granulosa lutein cells by providing androstenedione, which is then converted into estradiol by AROMATASE within granulosa lutein cells. Kierszenbaum, 3rd ed. A. Stevens, J.Lowe. Histologia,1994  Various fates of corpus luteum (CL) ◼ IF THE OOCYTE IS NOT FERTILIZED → hormone secretion ceases within 14 days after ovulation, CL degenerates into a corpus albicans - whitish scar tissue. Regression of CL is called luteolysis. ◼ IF THE OOCYTE BECOMES FERTILISED → Syncytiotrophoblast of the developing placenta secretes hCG, human chorionic Pawlina, Pawlina, Ross, Ross, 2020 2020 gonadotropin hormone, and hCS, human chorionic somatomammotropin A section of a normal ovary that was surgically (Placental Growth Hormone, PGH) removed during an oophorectomy. The corpus luteum is fully developed in the cortex of the ovary, which indicates the midluteal phase of the ovarian hCG stimulates LH receptors of corpus cycle. The cortex of the ovary contains atretic follicles, luteum and thus hormone secretion for 2-3 a small ovarian cyst, and a few corpora albicantia - months after ovulation remnants of corpora lutea from previous ovarian Progesterone and estrogens are required cycles. The medulla of the ovary contains a larger corpus to maintain the endometrium of the uterus albicans, which is most likely a remnant of the until 9-10th week of gestation. corpus luteum of pregnancy. ×2.  Corpus albicans If fertilization and implantation do not occur, the corpus luteum remains active only for 14 days; in this case, it is called the corpus luteum of menstruation. In the absence of human chorionic gonadotropin (hCG), the rate of secretion of progestogens and estrogens declines, and the corpus luteum begins to degenerate about 10 to 12 days after ovulation. Remnants from its regression are phagocytosed by macrophages, after which fibroblasts invade the area and produce a scar of dense connective tissue called a corpus albicans (L., white body).  CORPUS ALBICANS It is the scar of connective tissue that forms at the site of a corpus luteum after its involution. It contains mostly collagen, with few fibroblasts or other cells, and gradually becomes very small by the action of macrophages, and becomes lost in the ovarian stroma. Involution of the corpus luteum does not involve atresia. In the photomicrograph large amounts of hyaline material can be seen among the degenerating cells of the former corpus luteum. The corpus albicans is surrounded by ovarian stroma. ×125. Pawlina, Ross, 2020 Pawlina, Ross, 2020  ATRESIA. Most ovarian follicles are lost by atresia mediated by apoptosis of granulosa cells. DEGENERATION is shown in a follicle that had developed a large antrum. Atresia is characterized by apoptosis of granulosa cells (G) and autolysis of the oocyte, with macrophages entering the degenerating structure to clean up debris. Follicles at any stage of development, including nearly mature follicles, may Basic Histology, 12th ed. become atretic. Macrophages release IFNg and TNF which stimulate apoptosis. Many apoptotic cells are seen loose in the antrum (A) and the cells of the corona radiata have already disappeared, leaving the degenerative oocyte (O) free within the antrum. ◼ Infundibulum – Oviduct (fallopian tube, uterine tube) is fimbriated end composed of four parts ◼ Ampulla – usually site of fertilization ◼ Isthmus ◼ Intramural – traverses the uterus wall ◼ FUNCTION: conducts the oocyte from the ovary to the uterus - ovum remains in the oviduct for 3-6 days - peristaltic muscle action is more important for the Pawlina, Ross, 2020 transport of sperm and oocyte than the a. This cross-section is near the ampulla region of the uterine tube. The mucosa is thrown into extensive folds that project into the lumen of the tube. Branches of action of cilia the uterine and ovarian arteries (BV) travel along the uterine tube. ×16. b. The lumen of the tube is lined by a simple columnar epithelium composed of ciliated cells (above arrowhead) and nonciliated cells (below Pawlina, Ross,arrowhead). 2020 ×640.  Oviduct The wall of the oviduct (uterine tube) consists of : mucosa (folded; branching, longitudinal folds of the mucosa are most prominent in the ampulla), muscularis (thick; interwoven circular and longitudinal layers of smooth muscle), serosa. The mucosa is lined by the simple columnar epithelium containing: ciliated cells (ciliary movements sweep fluid toward the uterus) (a) A cross section of the uterine tube at the secretory peg cells (nonciliated; ampulla shows the interwoven circular (C) and secrete glycoproteins of a nutritive longitudinal (L) layers of smooth muscle in the mucus film that covers the epithelium). muscularis and in the complex of folded mucosa, They are most active state in the the lamina propria (LP) underlying a simple period shortly after ovulation when an columnar epithelium (arrows). (X140; H&E) (b) The oviduct mucosa, with folds embryo might be present projecting into the lumen (L), has simple Mescher A.L.(Ed.), (2018). Junqueira’s Basic columnar epithelium (E) on the lamina propria Histology: Text and Atlas, 15e. McGraw-Hill  Oviduct’s wall structure The MUCOSA ◼ Simple columnar epithelium: - ciliated cells and - Nonciliated, secretory = peg cells (nourish the oocyte and very early preimplantation embryo, secrete cytokines for capacitation of spermatozoa) ◼ Cell-rich lamina propria The MUSCULARIS ◼ an inner circular muscle layer ◼ an outer longitudinal layer ◼ an inner longitudinal layer - present in the isthmus and the intramural part The SEROSA is covered by simple squamous epithelium Kierszenbaum, 3rd ed.  Uterus GENERAL STRUCTURE: Adventitia (serosa, perimetrium) Myometrium: a fibromuscular layer Mucosa = endometrium FUNCTIONS: ◼ site of embryo and fetus development ◼ expels fetus at parturition (birth) ◼ passageway for sperm cells from cervix to oviduct Pawlina, Ross, 2020 Endometrium is divided into 2 zones based on their role in the menstrual cycle: General structure of endometrium BASALIS - not sloughed off during menstruation. It functions ❑ Covered by a simple columnar as a regenerative zone for the epith. (ciliated and secretory cells) functionalis after its rejection during menstruation. ❑ an underlying thick CT stroma is rich in cells that are embedded in FUNCTIONALIS - the luminal part of the endometrium, sloughed a network of reticular fibres. off during every menstruation. The epithelium invaginates into It is the site of cyclic changes of lamina propria to form many described as phases (stages) : simple tubular uterine glands proliferative (or follicular), extending through its entire secretory (or luteal), and thickness. menstrual. Stevens, Lowe, 1st ed. Changes in the histology of endometrium result from the changes in the blood levels of steroid hormones released from the ovaries during the menstrual cycle. The pituitary and ovarian hormones and their plasma concentrations are indicated in arbitrary units. FSH, follicle-stimulating hormone; LH, luteinizing hormone. Pawlina, Ross, 2020 Pawlina, Ross, 2020 Junqueira's Basic Histology, 14e, 2016: Hormonal regulation of ovarian function. Ovarian cycle of follicular growth, followed by ovulation and luteal formation, is initiated when hypothalamus secretes GnRH. This stimulates the anterior pituitary to secrete FSH and LH. Date of download: 3/18/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved. The both endometrial layers, the stratum basale and stratum functionale, are supplied by branches of the uterine artery. The spiral arteries located at the interface between these two layers degenerate and regenerate during the menstrual cycle under the influence of estrogens and progesterone. The uterine artery gives off 6 to 10 arcuate arteries that anastomose in the myometrium. Branches from these arteries, the radial arteries, enter the basal layer of the endometrium where they give off small straight arteries that supply this region of the endometrium. The main branch of the radial artery continues upward and becomes highly coiled; it is therefore called the spiral artery. Spiral arteries give off numerous arterioles that often anastomose as they supply a rich capillary bed. The capillary bed includes thin-walled dilated segments called lacunae. Lacunae may also occur in the venous system that drains the endometrium. The straight arteries and the proximal part of the spiral arteries do not change during the menstrual cycle. The distal portion of the spiral arteries, under the influence of estrogens and progesterone, undergoes degeneration and regeneration with each menstrual cycle. Pawlina, Pawlina, Ross, 2020 2020 Ross, Endometrium during the proliferative, secretory, and menstrual phases of menstrual cycle Upper panel (×15): during proliferative phase the stratum functionale (separated by the dashed line from the stratum basale) greatly thickens. In secretory phase note the pronounced corkscrew shape of the glands and mucus secretion (arrows) in b. ×60.. Lower panel shows the endometrial glands that extend from the stratum basale to the surface. ×55. Note the extra- vasated blood and necrosis of the stratum functionale at c. ×55. Pawlina, Ross, 2020 Pawlina, Ross, 2020  Summary of events of the menstrual cycle Stage of Cycle Proliferative Secretory or Luteal Menstrual Main Follicle-stimulating Peak of luteinizing hormone at the actions of hormone beginning of secretory stage, secreted after pituitary stimulates rapid estrogen stimulation, induces ovulation and growth of ovarian development of the corpus luteum hormones follicles Main events Growth of ovarian Ovulation Development Degeneration in the ovary follicles; dominant of the corpus of the corpus follicle reaches luteum luteum preovulatory stage Dominant Estrogens, Progesterone, produced by Progesterone ovarian produced by the the corpus luteum, acts production hormone growing follicles, mainly on the uterus ceases act on vagina, tubes, and uterus Main events Growth of the Further growth of the mucosa, coiling of Shedding of in the mucosa after glands, secretion part of the endometriu menstruation mucosa about 14 days after m  Cervix The mucosa of the cervical canal (CC) is continuous with the endometrium and is lined by the simple columnar epithelium (SC). The endocervical mucosa includes many large branched cervical mucous glands (arrows). At the external os, the point at which the cervical canal opens into the vagina (V), there is an abrupt junction (J) between the columnar epithelium and the stratified squamous epithelium (SS) covering the exocervix and vagina. Deeper, the cervical wall is primarily Mescher A.L.(Ed.), (2018). Junqueira’s Basic fibromuscular tissue (F). (X15; H&E) Histology: Text and Atlas, 15e. McGraw-Hill The lower portion of the cervix, the external os, Human cervix projects into the upper vagina whereas its middle and upper parts lead to the uterus through the cervical canal. The surface of the cervix is covered by stratified squamous epithelium (SSE). An abrupt transition endocervix from SSE to simple columnar epithelium (SCE) occurs at the entry to the cervical canal. TZ Before puberty and after menopause, the transformation zone (TZ) resides in the cervical canal as in this specimen. Mucus-secreting cervical glands are simple branched tubular glands. Frequently, the glands develop into nabothian cysts as a result of retention of mucus secretion by blockage of the gland opening. exocervix The material marked by the X is mucus secreted from the cervical glands. ×10. Pawlina, Ross, 2020 Metaplastic changes in this transformation zone (SCE instead of Pawlina, Ross, 2020 SSE in endocervix) constitute precancerous lesions of the cervix.  CERVIX OF THE UTERUS ◼ located between uterus and vagina Wall of the ◼ forms a barrier cervix is rich in between the collagen and internal and external elastic fibers, environment has only a few ◼ thick walled muscle fibers. branched tubular glands Functional Histology 2004. HE × 100  Uterine cervix,HE, x200 2 types of epithelium: simple columnar in endocervix and – in the vaginal portion (exocervix) - squamous stratified non- keratinized. Functional Histology 2004 Transformation zone of the cervix. Note Metaplastic stratified squamous epithelium of the abrupt change from SSE to SCE (arrow). the cervical canal is surrounded by the SCE SCE of cervical glands (CG) is connected normally found in the cervical canal. ×450 to lining epthelium of cervical canal. ×120 Pawlina, Ross. 2020 Pawlina, Ross, 2020 Neoplastic changes leading to development of cervical cancer most frequently begin in the transformation zone.  Vagina ◼ Fibromuscular tube ◼ Mucosa ❑ stratified squamous nonkeratinized epithelium ❑ Cell-rich cellular lamina propria with abundant lympho- cytes AND dense collagenous tissue below basal lamina Pawlina,Pawlina, Ross, 2020 Ross, 2020 ◼ Muscularis The epithelial connective SSE cells have small pyknotic nuclei. ❑ Inner circular and tissue boundary is Note a single layer of basal cells and outer longitudinal two or three layers of cells undergoing layers of smooth typically very irregular, differentiation (with eosinophilic muscle fibers. with prominent papillae cytoplasm). The tips of the papillae of ◼ Adventitia projecting into the the connective tissue often appear as undersurface of the isolated structures surrounded by NO GLANDS IN epithelium. x 40. epithelium (arrows). ×180. VAGINA!!!  Cervical cytology = Pap test. Superficial epithelial cells are removed from the mucosa, added to a liquid medium, and sent to a laboratory for microscopic examination. Before the advent of liquid-based cervical cytology, cervical cell samples were spread on glass slides and stained with the Papanicolaou stain (a combination of hematoxylin, orange G, and eosin azure). Pap staining provides valuable diagnostic information about the epithelium regarding pathologic changes, response to hormonal changes during the menstrual cycle, and the microbial environment of the vagina. Pawlina, Ross, 2020 Pawlina, Ross, 2020 a. Negative cervical cytology. The surface squamous cells reveal small pyknotic nuclei and abundant cytoplasm. Other cells include red blood cells and neutrophils. b. ABNORMAL CYTOLOGY. Many of the cells contain large nuclei with no evidence of pyknosis (arrows). The cytoplasm is relatively scant. Other cells exhibit a more normal appearance with pyknotic nuclei and more surrounding cytoplasm (arrowheads). Neutrophils are also present. x600  Pap cervical smears is a standard procedure for the early detection of cervicovaginal malignancies Kierszenbaum, 3rd ed.  Pap cervical smears is a standard procedure for the early detection of cervicovaginal malignancies Kierszenbaum, 3rd ed.  External genitals are collectively known as the vulva ◼ labia minora - thin hairless folded skin just outside the vaginal opening ◼ labia majora - cover and protect the genital area ◼ clitoris - a small erectile organ, homologous to the penis Its body is composed of two small conjoined erectile bodies, the corpora cavernosa; the glans clitoris, a small, rounded tubercle at the tip of corpora cavernosa; and two crura of the clitoris that firmly anchor the clitoris to the pubic rami. Pawlina, Ross, Pawlina, Ross.2020 2020 Inner surface of the labia majora shows its The skin over the glans is very thin, forms nonkeratinized epithelium (Ep) and abundant the prepuce of the clitoris, and contains sebaceous glands (SG). Two sebaceous ducts (SD) are also evident. At this low magnification, numerous sensory nerve endings. several smooth muscle bundles can just barely be discerned (arrows).