Lecture 02

THE UTERINE/ MENSTRUAL CYCLE AND ITS HORMONAL CONTROL

By:

A. Prof. Dr Farooq A. Khan PMC

12th Dec. 2019 UTERUS

 Hollow, flattened, thick walled muscular organ.

 Consists mainly of :  BODY  CERVIX  FUNDUS

 DIMENSIONS =  8 cm long,  4 cm wide,  2 cm thick, in a non-pregnant state Parts of UTERUS

 BODY = forms upper 2/3, Pear shaped

 CERVIX = forms lower 1/3, Narrow, Cylindrical shaped

 UTERINE TUBES = are attached to the upper part of the body

 FUNDUS = Part of the body above the attachment of the uterine tubes CERVIX

Cervix:The cylindrical inferior one third.  1-cm-long constricted region between the body and the cervix  The lumen of the cervix cervical canal, has a constricted opening at each end.  The internal os (opening) of the uterus communicates with the cavity of the uterine body and the external os communicates with the vagina. UTERUS

 Histologically uterine wall has 3 major layers.

 PERIMETRIUM: Outer layer

 MYOMETRIUM: Middle layer

 ENDOMETRIUM: Inner layer Female reproductive system

 Wall of uterus has three layers:

 1.Outer layer, serosa (perimetrium).

 2. Middle layer, muscularis (myometrium).

 3. Inner layer, mucosa (endometrium). PERIMETRIUM

 Is part of visceral peritoneum Female reproductive system

 Myometrium

 Smooth muscle, 12 to 15 mm in thickness.

 Muscle fibers are arranged in bundles, separated by c. tissue.

 During pregnancy fibers increase greatly in number & size. (hyperplasia and hypertrophy)

 In spite of increase in muscle mass, myometrium is thinned during pregnancy. Female reproductive system

 Three layers of muscle may be distinguished, although ill-defined due to presence of interconnecting bundles:

 1. An inner muscular layer, mostly of longitudinally arranged fibers, stratum subvasculare

 2. A thick middle layer, circular & oblique ms. fibers with numerous b. vs, stratum vasculare.

 3. An outer, thin, longitudinal muscle layer immediately beneath perimetrium, stratum supravasculare Female reproductive system

 Endometrium (mucosa),

 Firmly adherent to underlying myometrium, goes under cyclic changes in response to ovarian secretory activity.

 These changes result in partial destruction of mucosa, leading to tissue necrosis & hemorrhage,  menstruation. ENDOMETRIUM

 Inner lining of the uterine cavity, consists of:  1. EPITHELIUM:

 2. LAMINA PROPRIA: Contain simple tubular glands which are invaginations of surface epithelium and penetrate as deep as myometrium. ENDOMETRIUM

EPITHELIUM:

 SURFACE EPITHELIUM: Ciliated and Secretory Simple Columnar

 GLANDULAR EPITHELIUM: Is similar to surface epithelium with rare ciliated cells ENDOMETRIUM

LAMINA PROPRIA:

 Highly cellular embryonic type of C.T.

 Abundant ground substance

 Fibers mostly reticular

 Contains blood vessels and lymphatic spaces filling the gaps between the endometrial glands ENDOMETRIUM

 Endometrium at the peak of development is 5–6 mm thick and divided into 2 strata 1.STRATUM FUNCTIONALIS:  Layer closest to the uterine cavity and is shed during menstruation and parturition, is responsive to ovarian hormones.  Stratum Compactum  Stratum Spongiosum ENDOMETRIUM

2.STRATUM BASALIS:  Is the deeper layer and is permanent (retained after menstruation).  It gives rise to a new Stratum Functionalis after each menstruation.  Important aspect of menstruation are spiral arteries that feed the endometrium.  When estrogens and progesterone levels drop, spiral arteries constrict and results in ischemia of the Stratum Functionalis layer. ENDOMETRIUM

BLOOD SUPPLY:  Uterine Arteries: enter myometrium.

 Arcuate Arteries: anterior and posterior, ramify as they run circumferentially in stratum vasculare and approach the anterior and posterior midline. ENDOMETRIUM

BLOOD SUPPLY cont’ d:

 Radial Arteries : pass radially into endometrium and divides into…….

 Straight Arteries:  Supply stratum basale

 Coiled (spiral) Arteries:  Supply stratum functionalis UTERINE TUBES  Two in number, lie on each side of uterus in the upper margin of the broad ligament

 Each is 10 cm long and opens medially into the uterus and laterally into abdominal cavity through apertures called Uterine os and Abdominal os respectively.

Uterine Tubes UTERINE TUBES

 DIVIDED INTO FOUR PARTS:

1. FIMBRIATED END (Infundibulum)

2. AMPULLARY: It forms more than the lateral half of the tubal length. Has thin walls and complexly folded luminal surface. Lumen about 1cm in diameter.

FERTILIZATION TAKES PLACE IN THIS REGION OF UTERINE TUBE. UTERINE TUBES

3. ISTHMUS: It is rounded, muscular and firm, It forms approx. the medial third.

Lumen narrow ( 0.1- 0.5 mm). Luminal folds much less complex.

4. INTRAMURAL (Intrauterine) MORPHOLOGY OF UTERINE TUBE  MUCOSA, MUSCULARIS and SEROSA

 Epithelium is Simple / Pseudostratified Columnar comprising of:

 CILIATED CELLS:  Cilia beat towards the uterus.

 SECRETORY Cells:  Secrete thick, tenacious mucus.  It has nutritive and protective role for the ovum and promotes CAPACITATION of spermatozoa. MORPHOLOGY OF UTERINE TUBE

 PEG – CELLS (Intercalary):  It may represent Secretory cells in a non – Secretory phase or immature ciliated cells.

 NOTE:  Women suffering from immotile cilia syndrome are usually fertile showing that ciliary activity is not required for transport. OVARIES

 The ovaries are almond-shaped reproductive glands located close on each side of the uterus that produce oocytes.

 The ovaries also produce estrogen and progesterone which is responsible for:

 The development of secondary sex characteristics and regulation of pregnancy.

 Suspended with the uterus with the Ovarian ligament.

THE UTERINE (MENSTRUAL) CYCLE

PART - II CORPUS LUTEUM

 After ovulation, walls of the empty follicle collapse and thrown into folds.

 Granulosa cells increase in size (30-40μm), and contain a bright yellow pigment (lutein).

 Basal lamina breaks down and theca interna cells along with capillaries and CT infiltrate the folds.

 Blood clot in the centre – resolves.

 GRANULOSA LUTEIN CELLS  THECA LUTEIN CELLS CORPUS LUTEUM

 IF OOCYTE IS FERTILISED:  CL enlarges to form the CORPUS LUTEUM OF PREGNANCY (10mm-25mm) and increases its hormone production.

 During pregnancy degeneration of CL is prevented by hCG.

 Remains functional for 20 weeks, then placenta takes over. MENSTRUAL CYCLE

 Endometrium shows morphological and functional changes in each menstrual cycle.  Average menstrual cycle is 28 days, with day 1 of the cycle designated as the day on which menstrual flow begins.  Menstrual cycles vary in length by several days in normal women.

 In 90% of women, length of the cycles ranges between 23 and 35 days.

 Almost all these variations result from alterations in the duration of the proliferative phase of the menstrual cycle. Progesterone declines causing to loss of decidua support leading to menses  Cyclic changes of the endometrium, regulated by MENSTRUAL CYCLE cyclic production of estrogen and progesterone

 Three (or 04) successive phases

 1. MENSTRUAL PHASE – loss of St. Functionalis

 2. PROLIFERATIVE PHASE – regeneration of functional layer

 3. SECRETORY PHASE – endometrium increases in size & readies for implantation. This phase lasts as long as the corpus luteum is intact & producing progesterone. (4.Ischemic phase)

 These phases are part of a continuous process; each phase gradually passes into the next one. MENSTRUAL PHASE

 Lasts for 4 – 5/8 days  Begins the menstrual cycle

 Degeneration of most of Stratum functionalis of endometrium ( 2/3 – 3/4 of thickness of endometrium )

 Triggered by decline in progesterone and estrogen due to disintegration of corpus luteum MENSTRUAL PHASE

 Endometrial arteries constrict, blood flow is reduced

 St. Functionale is shed off  Weakened arteriole walls collapse, releasing blood

 Blood and endometrial debris pass through vagina to exterior  Stratum basale is retained PROLIFERATIVE PHASE

 Begins after completion of menses.  Lasts about 9 days  Surviving epithelial and stromal cells proliferate by mitosis.  Epithelial cells in the basal portion of glands migrate to cover the denuded endometrial surface.  Stimulated by rising estrogen due to growth of ovarian follicles  By ovulation, endometrium is about 3mm thick  Glands have narrow lumina, relatively straight, having a slight wavy appearance, secreting watery mucus SECRETORY PHASE  Begins at the time of ovulation and lasts for about 13 days  Coincides with the formation, functioning and growth of corpus luteum

 Progesterone secreted by CL  1. Stimulates glandular epithelium to secrete material rich in glycogen  2. Glands dilate, tortuous (saw tooth / corkscrew appearance)  3. Endometrium is oedematous and thickens (up to 6 mm)  4. Spiral arteries become increasingly coiled SECRETORY PHASE - GLANDS

EARLY SECRETORY:

 Glycogen in basal cytoplasm.  Nuclei centrally placed.  Giant Mitochondria,  RER, Golgi and  Secretory vesicles supranuclear. SECRETORY PHASE - GLANDS

MID SECRETORY:  Basal glycogen shifts to apical cytoplasm,  Nuclei shift basally.  Golgi dilated and secrete glycogen,  Mucin and other glycoproteins – released to glands lumina – apocrine & exocrine

LATE SECRETORY:  Glandular activity declines SECRETORY PHASE IF NO FERTILISATION THEN ISCHAEMIC PHASE:  Ischaemia gives endometrium a pale appearance  Spiral arteries constrict and relax intermittently  Stoppage of glandular secretion and loss of interstitial fluid  shrinkage of endometrium towards the end of the phase:  Spiral arteries go into spasm for longer period of time, blood seeps into surrounding stroma, small pools of blood form, break through epithelium which result in bleeding and the new cycle starts

IF FERTILISATION OCCURS:  Blastocysts embeds and the menstrual cycle stops SIGNS OF OVULATION

 CHANGES in CERVICAL MUCUS

 CERVIX SOFTENS

 MITTELSCHMERZ (ovulation pain)–  A variable amount of abdominal pain, accompanies ovulation in some women. In these cases, ovulation results in slight bleeding in the peritoneal cavity, which results in sudden constant inferolateral pain in the abdomen.  Mittelschmerz may be used as a symptom of ovulation, but there are better symptoms, such as the……,

 BASAL BODY TEMPERATURE – which usually shows a slight drop followed by a sustained rise after ovulation FEMALE REPRODUCTIVE CYCLES and Hormonal Changes.

 At puberty, females undergo reproductive cycles.

 Which involve activities of the hypothalamus of the brain, pituitary gland, ovaries, uterus, uterine tubes, vagina, and mammary glands.

 These monthly cycles prepare the reproductive system for pregnancy. FEMALE REPRODUCTIVE CYCLES and Hormonal Changes.

 A gonadotropin-releasing hormone (Gnrh) is synthesized by neurosecretory cells in the hypothalamus.

 The Gnrh is carried by the hypophysial portal system to the anterior lobe of the pituitary gland.

 This hormone stimulates the release of two hormones produced by this gland that act on the ovaries. Hormones

 Follicle-stimulating hormone (FSH)  It stimulates the development of ovarian follicles and the production of estrogen by the follicular cells.

 Luteinizing hormone (LH)  It serves as the “trigger” for ovulation (release of secondary oocyte) and stimulates the follicular cells and corpus luteum to produce progesterone.  These hormones also induce growth of the ovarian follicles and the endometrium. OVARIAN CYCLE

 FSH and LH produce cyclic changes in the ovaries.  Development of follicles ovulation, and corpus luteum formation.

 During each cycle, FSH promotes growth of several primordial follicles into 5 to 12 primary follicles.  However, only one primary follicle usually develops into a mature follicle and ruptures through the surface of the ovary, expelling its oocyte.