Histology of the Female Reproductive Tract PDF

Histology of the female reproductive tract Joyce El-Haddad [email protected] @orientatewithjoyce Lecture Outline • Overview of the female reproduc3ve tract • Ovary • Uterine Tube • Uterus • Cervix • Vagina • Mammary Glands • Clitoris Overview of the female reproductive tract Ovary • 2 o...

Histology of the female reproductive tract Joyce El-Haddad [email protected] @orientatewithjoyce Lecture Outline • Overview of the female reproduc3ve tract • Ovary • Uterine Tube • Uterus • Cervix • Vagina • Mammary Glands • Clitoris Overview of the female reproductive tract Ovary • 2 ovaries • Almond shaped glands located on the lateral walls of the lesser pelvis • Histologically, consists of a cortex and medulla. • Function: ØProduction of gametes ØProduction of hormones (oestrogen, progesterone, relaxin) Histology of the ovary • Ovarian surface is covered by germinal epithelium/ovarian surface epithelium • The ovary is poorly divided into an outer cortex and an inner medulla • Under the surface epithelium = DICT aka the tunica albuginea CORTEX AND MEDULLA OF OVARY • The cortex is normally filled with numerous ovarian follicles in various stages of development. • Medulla = highly vascularized region • Demarcation between cortex and medulla = ambiguous. Ovarian Cortex The ovarian cortex contains: 1. 2. 3. 4. Stroma Ovarian follicles Corpus luteum Corpus albicans Menstrual Cycle Primordial follicles Light micrograph (LM) of the surface of the ovary. The ovarian surface epithelium (OSE) consists of one layer of cuboidal to columnar cells. A basement membrane separates them from underlying tunica albuginea (TA). 390×. H&E. Primordial follicles FC LM of part of the ovarian cortex. Markedly cellular connective tissue stroma surrounds primordial (PF), primary (1F), and secondary (2F) ovarian follicles. 295×. H&E. FC O O Stroma LM of a primordial follicle in the ovarian cortex. One layer of squamous follicular cells (FC) surrounds a primary oocyte (O). The oocyte has a large vesicular nucleus. The clear space between oocyte and follicular cells is a cell shrinkage-related preparation artifact. 790×. H&E. LM of a primary follicle. One layer of cuboidal follicular cells (FC) envelops an oocyte (O). Surrounding stroma is highly cellular and contains elongated cells, some of which will become theca interna cells. The space between oocyte and follicular cells is a preparation artifact. 790×. H&E. Primordial Follicles • Primordial follicles are formed during fetal life • They have 3 major components: 1- A primary oocyte with a large nucleus and prominent nucleolus 2- Follicular cells: A single layer of the flattened cells (squamous cells) enveloping the primary oocyte 3- Basal lamina: • Surrounds the follicular cells • Marking a clear boundary between the follicle and the vascularized stroma and acts as a blood-follicle barrier • These follicles are located just underneath the tunica albuginea • After puberty, 20 primordial follicles become activated during the menstrual cycle each month (Gonadotropin Releasing Hormone DEPENDENT) • On average, one follicle from here becomes dominant and goes on to become a primary follicle • BEFORE puberty, some primordial follicles can develop into primary under the influence of GH. This is Gonadotropin Independent Recruitment. Primary Follicles PF Primary follicles TA (X200; PT; Primary follicles) • PF: primordial follicles • UF: unilaminar primary follicles • F: follicle cells • Arrows: epithelial follicular cells 2F Stroma (X200; PSH; A multilayered primary follicles) (activeof follicular cells) cortex. Markedly cellular connective tissue LMcells of part the ovarian Light micrograph (LM) of the surface of the ovary. The ovarian• G: granulosa • O: oocyte stroma surrounds primordial (PF), primary (1F), and secondary (2F) ovarian surface epithelium (OSE) consists of one layer of cuboidal to columnar cells. • ZP: zona pellucida follicles.membrane 295×. H&E. A basement membrane separates them from underlying tunica albuginea • BS: basement (TA). 390×. H&E. FC FC O O Stroma LM of a primordial follicle in the ovarian cortex. One layer of squamous follicular cells (FC) surrounds a primary oocyte (O). The oocyte has a large vesicular nucleus. The clear space between oocyte and follicular cells is a cell shrinkage-related preparation artifact. 790×. H&E. LM of a primary follicle. One layer of cuboidal follicular cells (FC) envelops an oocyte (O). Surrounding stroma is highly cellular and contains elongated cells, some of which will become theca interna cells. The space between oocyte and follicular cells is a preparation artifact. 790×. H&E. Histology of primary follicles • Stromal (supporting) cells immediately outside each growing primary follicle • Differentiate to form the two distinct vascularized tissue around the follicle: 1. 2. Theca interna § A well-vascularized endocrine tissue § With typical steroid-producing cells secreting androstenedione § Nuclei = round Theca externa § A fibrous tissue with fibroblasts, macrophages, and smooth muscle merges gradually with the surrounding stroma § Nuclei = flat Zona pellucida: • A layer between oocytes and follicular cells • Containing 4 glycoproteins (ZP1, ZP2, ZP3, ZP4) secreted by the oocyte. (X200; PSH; A multilayered primary follicles [monkey]) • GC: granulosa cells • ZP: zona pellucida Primary follicles • Slightly larger than primordial follicles • The oocyte is now surrounded by cuboidal cells which have a busy cytoplasm – a granular appearance. • The cuboidal granular cells = granulosa cells. • The stromal tissue around the follicle differentiates into a concentric sheath of theca interna cells. (TI) • TI have receptors for luteinizing hormone How to spot a primary follicle: Growth of a small group of primordial follicles each month (beginning in puberty): 1. Growth of the oocyte 2. ProliferaJon and changes in the follicular cells There are two types of primary follicles: • Unilaminar primary follicle: § A simple cuboidal epithelium (follicular cells) around the growing oocyte • MulJlaminar primary follicle: § A straJfied follicular epithelium (granulosa) § Follicular cells: now termed granulosa cells (sJll avascular and surrounded by a basement membrane) Secondary Follicle Secondary (Antral) Follicles • As the primary follicles grow, they move deeper into the ovary cortex • From here we get the secondary follicles • They are demarcated by the presence of an antrum (cavity) (X100; H&E; Antral follicle) • A: antrum • O: oocyte • ZP: zona pellucida • G: granulosa cells • TI: theca interna • TE: theca externa (X100; PT; A slightly more developed antral follicle) • A: antrum • O: oocyte • CR: corona radiata • CO: cumulus oophorus • G: granulosa layer • TI: theca interna • TE: theca externa Histological features of the secondary follicle 1- Primary Ooctye 2- Granulosa cells - 3 locations – 3 descriptions: A. Stratum granulosum: Line the follicular wall B. Cumulus oophorus: The hillock of granulosa cells around the oocyte C. Corona radiata: The tightly adhering granulosa cells immediately surrounding the zona pellucida Leave with the oocyte at ovulation 3- Antrum – fluid filled cavity 4- Follicular theca: A. Theca interna – receptors of LH B. Theca externa (X100; H&E; Antral follicle) • A: antrum • O: oocyte • ZP: zona pellucida • G: granulosa cells • TI: theca interna • TE: theca externa (X100; PT; A slightly more developed antral follicle) • A: antrum • O: oocyte • CR: corona radiata • CO: cumulus oophorus • G: granulosa layer • TI: theca interna • TE: theca externa (X400; PT; Wall of antral follicle) • A: antrum • G: granulosa cells • BS: basement membrane • TI: theca interna • TE: theca externa • S: stroma Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X85; H&E; Secondary/antral follicle) • A: antrum • GC: granulosa cells • TI: theca interna • TE: theca externa Mature Follicle Mature (Graafian) Follicle Features: 1- germ cell/gamete: • Secondary oocytes 2- granulosa cells: A. Membrana granulosa / Stratum granulosum B. Cumulus oophorus C. Corona radiata (ovulate with the oocyte) 3- Antrum: a single large vesicle • Rapidly accumulates more follicular fluid • Expands to a diameter of 2cm • Forms a bulge at the ovary surface visible with ultrasound imaging 4- Follicular theca: A. Theca interna B. Theca externa Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X45; H&E; Mature Graaffian follicle) • A: antrum • CO: cumulus oophorus • SG: stratum granulosum • TI: theca interna Ovulation • A hormone-stimulated process by which the oocyte is released from the ovary • Dominant follicle usually reaches the most developed stage of follicular growth and undergoes ovulation, while the other primary and antral follicles undergo atresia • Normally occurs midway through the menstrual cycle (around the 14th day of a typical 28-day cycle) @orientatewithjoyce Corpus Luteum A temporary endocrine gland in the ovarian cortex Formed by: 1- Granulosa cells • Change to granulosa lutein cells • Invaded by capillaries • Increase greatly in size, without dividing, and eventually comprise about 80% of the CL • Secrete large amounts of oestrogen, progesterone, and inhibin 2- Theca interna • Change to theca lutein cells • Half the size of the granulosa lutein cells • Typically aggregated in the folds of the wall of CL • Becomes well vascularized • Produce large amounts of progesterone and androstenedione (X15; H&E; Corpus Luteum) • CL: corpus Luteum • BC: blood clot (X100; H&E; Corpus Luteum) • GL: Granulosa lutein cells • TL: theca lutein cells Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health Female human corpus luteum of menstruation Corpus Luteum in pregnancy If pregnancy occurs: • Uterine mucosa does not undergo menstruation to prevent spontaneous abortion of pre-embryo. • Production of human chorionic gonadotrophin (hCG) by embryo § Maintains and promotes further growth of the corpus luteum At months 4-5 of pregnancy: • Production of progesterone (and estrogens) at levels adequate to maintain the uterine mucosa by placenta • CL degenerates and is replaced by a large corpus albicans Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X12; H&E; Human corpus Luteum) • Cav: follicular cavity • Arrows: theca interna (X240; H&E; Human corpus Luteum) • GLC: granulosa lutein cells • TLC: theca lutein cells Corpus Albicans Without further LH s.mula.on and in the absence of pregnancy: • • Reduced steroid produc8on in CL Apoptosis and regression of CL (X60; H&E; Corpus albicans) • CA: corpus albicans Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X125; H&E; Corpus albicans of a human ovary) Follicular Atresia Follicular atresia • Degenerative process happens in most ovarian follicles: § Apoptosis § Removal by phagocytic cells Ovarian reserve when menopause begins: >1000 follicles What histological features do you noJce here? (X200; PT; An atretic follicle) • GC: apoptotic granulosa cells • O: degenerative oocyte • A: antrum UTERINE TUBES (Oviducts) Four regions in the following sequence from ovarian end to uterine end: 1- Infundibulum: • Fringed with finger-like extensions called fimbriae proximal to the ovary 2- Ampulla: • The longest and expanded region • Where fertilization normally occurs 3- Isthmus: a more narrow portion proximal to the uterus 4- Uterine / intramural part: • Passes through the wall of the uterus • Opens into the uterine cavity UTERINE TUBES (Oviducts) 1- Mucosa: • Numerous branching, longitudinal folds which are most prominent in the ampulla • Smaller in the regions closer to the uterus and are absent in the intramural portion of the tube Epithelium: simple columnar epithelium § Ciliated cells: ü Ciliary movements sweep fluid toward the uterus § Secretory peg cells: ü Non-ciliated and often darker staining ü Secrete glycoproteins of a nutritive mucus Lamina propria: loose connective tissue 2- Muscularis: Thick, with interwoven circular (or spiral) and longitudinal layers of smooth muscle 3- Serosa: Thin, covered by visceral peritoneum with mesothelium UTERINE TUBES (Oviducts) (X140; H&E; Uterine tube wall) • C: circular layer of smooth muscle • L: longitudinal layer of smooth muscle • LP: lamina propria • Arrows: simple columnar epithelium (X200; PT; Oviduct mucosa) • E: simple columnar epithelium • LP: lamina propria • L: lumen (X400; PT; Oviduct epithelium) • CC: ciliated cells • PC: peg cells UTERINE TUBES (Oviducts) Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X16; H&E; Human uterine tube) • BV: blood vessels (X640; H&E; Human uterine tube) • Above the point of the arrow: ciliated cells • Below the point of the arrow: non-ciliated cells UTERUS Three histological layers: 1- Endometrium / Mucosa 2- Myometrium 3- Perimetrium UTERUS HISTOLOGY: Endometrium The Mucosa/endometrium of the uterus consists of: Epithelium: simple columnar epithelium • Ciliated cells • Secretory cells Lamina propria or stroma Zones of endometrium: A. Stratum Functionalis (Functional layer): undergoes profound changes during the menstrual cycles B. Stratum Basale (Basal layer): remains relatively unchanged during the menstrual cycles Two types of arteries in endometrium: 1- Straight arteries: supply only the basal layer 2- Spiral arteries: progesterone-sensitive; bring blood throughout the functional layer Endometrium (X100; Mallory trichrome; Basal layer of endometrium) • B: basal layer • G: uterine glands • A: arteries • M: myometrium (X100; Mallory trichrome; Functional layer of endometrium) • G: uterine glands • A: arteries (X400; Mallory trichrome; Functional layer of endometrium) • SE: surface epithelium • S: stroma UTERUS HISTOLOGY: Myometrium and Perimetrium Myometrium: • A thick tunic of highly vascularized smooth muscle • Interwoven layers, with fibers of the inner and outer layers Perimetrium: • Largely: serosa covered by mesothelium • In some areas: adventitia (X100; Mallory trichrome; Basal layer of endometrium) • B: basal layer • G: uterine glands • A: arteries • M: myometrium Changes in the endometrium Secretory Proliferative Menstrual a (upper panel: X15; lower panel: X55; Proliferative phases) b (upper panel: X20; lower panel: X60; Secretory phases) • Arrows: mucus secretion c (upper panel: X15; lower panel: X55; Menstrual phases) Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health Menstrual ProliferaJve Secretory Changes in the endometrium 1. Proliferative/Follicular/Estrogenic Phase • 8-10 days on average • Increase in the thickness of uterine mucosa (from ~0.5 mm to 2-3 mm thick) • Coincides with the rapid growth of a small group of ovarian follicles growing as vesicular follicles • Estrogens act on the endometrium, inducing regeneration of the functional layer lost during menstruation 2. Secretory/luteal Phase • Starts as a result of the progesterone secreted by the corpus luteum • Maximum thickness (5 mm) of endometrium during the secretory phase as a result of the accumulation of secretions and edema in the stroma 3. Menstrual Phase • Day 1 of the menstrual cycle = the day when menstrual bleeding appears • Lasts 5 days on average • Caused by reduced circulating levels of progesterone and estrogens when fertilization and implantation do not occur/regression of the corpus luteum Cervix (X35 and X400; H&E) o Lower, cylindrical part of the uterus o Extending between internal and external os: • Cervical canal Histologically: 1- Endocervical mucosa 2- Exocervical mucosa (X45; H&E) Cervix (X120; H&E; Exocervix) (X120; H&E; Transformation zone of the cervix) • Arrow: junction between epithelia • CG: mucus-secreting cervical glands (X10; H&E; Human cervix; a postmenopausal woman) • SCE: simple columnar epithelium • SSE: stratified squamous epithelium • X: mucus secreted from the cervical glands Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health VAGINA 1- Mucosa: • Epithelium: § Non keratinised stratified squamous epithelium § When the cells desquamate, bacteria metabolize glycogen to lactic acid, causing a relatively low pH within the vagina • Lamina propria: § No glands; mucus in the vagina is produced by the cervical glands 2- Muscular layer: • Two indistinct layers of smooth muscle: § Circular bundles: next to the mucosa § Longitudinal bundles: near the adventitia 3- Adventitia: • Rich in elastic fibers • Contains an extensive venous plexus, lymphatics, and nerves (X60; H&E; Vagina) • E: epithelium • LP: lamina propria • M: muscular layer (X200; PSH; Vagina mucosa) • LP: lamina propria VAGINA Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health (X40; H&E; Human vagina) External Genitalia / Vulva Include several structures, all covered by stratified squamous epithelium: Vestibule • A space whose wall includes the tubuloacinar vestibular glands Labia minora • Folds of skin lacking hair follicles but with numerous sebaceous glands Labia majora • Homologous and histologically similar to the skin of the scrotum Clitoris • An erectile structure homologous to the penis with paired corpora cavernosa (H&E; Inner surface of the labia minora) • Ep: non-keratinised stratified squamous epithelium • SG: sebaceous glands • SD: sebaceous ducts • Arrows: smooth muscle bundles Source: Michael H. Ross: Histology: a Text and Atlas, 7th Edition Copyright © 2016 Wolters Kluwer Health Mammary Glands Highly modified apocrine sweat glands Each mammary gland: • 15-25 lobes of the compound tubuloalveolar type Each lobe: • Consists of many lobules, sometimes called terminal duct lobular units (TDLU) • A separate gland with its own excretory lactiferous duct Histologic structure: • During Puberty (nonpregnant adults) • During Pregnancy & Lactation • Post-lactational Regression in the Mammary Glands Breasts During Pregnancy & Lactation (X60; H&E; Adult, nonpregnant female) • L: lobule • CT: connective tissue (X60; H&E; during pregnancy) • L: lobule • CT: connective tissue • A: adipocyte (X60; H&E; during lactation) • A: glandular alveoli • D: excretory ducts • Arrows: small septa Actively Developing and Lactating Alveoli (X400; H&E; Glandular alveoli) • A: alveoli • M: myoepithelial cells • D: intralobular ducts • Arrow: milk • L: lymphocytes • V: venules • P: plasma cells (X400; PT; Glandular alveoli) • LD: lipid droplet • V: venule • CT: connective tissue