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MENSTRUAL CYCLE Learning Objectives At the end of the tutorial, the student should be able to : • Define menstrual cycle. • Tell us the duration of menstrual cycle. • Describe the physiologic changes that occur in the female reproductive organs during the menstrual cycle. • Explain the regulation of menstrual cycle. • Express the applied physiology Menstrual Cycle Definition: Periodic vaginal bleeding that occurs with the shedding of the uterine mucosa (menstruation). Menstruation • Indicate periodic shedding of the stratum functionale of the endometrium, which becomes thickened prior to menstruation under the stimulation of ovarian steroid hormones. A : Functional Layer. B: Basal layer. Duration of the cycle • Variable, • an average figure is 28 days from the start of one menstrual period to the start of the next. • First day of menstruation “day one “ of the cycle. Timing events in the menstrual cycle. 1. Onset of menstruation 0 4 8 12 16 20 24 28 Phases of the menstrual Cycle Changes in ovary : – THE FOLLICULAR PHASE: From first day of menstruation until day of ovulation. – LUTEAL PHASE: After ovulation is luteal phase until first day of menstruation Phases of the menstrual Cycle • Changes in the endometrium: – Menstrual , – Proliferative and – Secretory Phase Ovarian Cycle • Follicular Phase ( Day 1 to Day 13 ): – Menstruation lasts from 1 to day 4 or 5 of the average cycle. – Secretion of Ovarian steroid hormones are at their lowest. – Ovaries contain only primary follicles. • Follicular Phase ( Day 1 to Day 13 ): – Some primary follicles grow, and become secondary follicles. – Towards the end , one follicle in one ovary reaches maturity and reaches graffian follicle. – As follicles grow, the granulosa cells secrete estradiol ( the principal estrogen), which reaches its highest concentration in the blood at about day 12 of the cycle, 2 days before ovulation. Growth of follicles: Antral follicle Graafian follicle Primordial follicle Oocyte Granulos a cells Antrum (fluid filled space) Thecal cells Ovulation Key events in the ovarian cycle LH 2. Ovulation 0 4 1. Follicular Day growth 1 8 12 16 Menstruation • 20 24 3. Luteal function 28 Oestradi ol 4. Luteal regressi on Progesterone (and OVULATION oestradiol) Follicular Phase ( Day 1 to Day 13 ): – Growth of follicles and secretion of estradiol are stimulated by FSH. – FSH in early follicular phase is slightly greater then in late follicular phase. – Towards the end , FSH and estradiol also stimulate the production of LH receptors in the graffian follicle. – Graafian follicle is prepared for the next major event. LH Surge • Begins about 24 hours before ovulation. • Reaches its peak 16 hours before ovulation. • LH surge acts to trigger ovulation. Positive feedback effect of estradiol on the pituitary , an increase in LH secretion in late follicular phase culminates in an LH s. Timing events in the menstrual cycle. 2. LH surge LH Ovulation • LH Surge causes graafian follicle to rupture at about day 14. • Secondary oocyte arrested at metaphase II of meiosis , is released from ovary into the uterine tube. • Ovulation occurs Luteal phase • After Ovulation, the empty follicle is stimulated by LH to become corpus luteum. • Corpus luteum secretes both estradiol an progesterone. • Progesterone levels in the blood are negligible before ovulation but rise rapidly to a peak level during the luteal phase, approximately one week after ovulation • Progesterone with estradiol during the luteal phase exert an inhibitory, or negative feedback effect on FSH n LH secretion. • Corpus luteum produces inhibin which may help to suppress FSH secretion. • This retards the development of new follicles. • Further ovulation does not occur. • Multiple ovulations and possible pregnancies on succeeding days of cycle are prevented. • New follicles develop towards the end of one cycle in preparation for the next. • Inhibin production is decreased at the end of luteal phase. • Estrogen and progesterone levels also fall during the late luteal phase ( starting about day 22) because corpus luteum regresses and stops functioning. • With the declining function of corpus luteum, esterogen and progesterone fall to very low levels by day 28 of the cycle. WITHDRAWL OF OVARIAN STEROIDS CAUSES MENSTRUATION AND PERMETS A NEW CYCLE OF FOLLICLE DEVELOPMENT TO PROGRESS Cyclic changes in the Endometrium • Development of the endometrium is timed by the cyclic changes in the secretion of estradiol and progesterone from the ovarian follicles. • Three phases can be identified: – The proliferative phase. – The secretory phase. – The menstrual phase The proliferative Phase • occurs while the ovary is in follicular phase. • Increasing amounts of estradiol stimulate proliferation of stratum functionale of the endometrium. • Spiral arteries develop in the endometrium. • Estradiol stimulates the production of receptor proteins for progesterone at this time, in preparation for the next phase of the cycle. The secretory phase • Occurs when ovary is in its luteal phase. • Increased progesterone secretion stimulates the development of uterine glands. • Endometrium becomes thick, vascular and ‘ spongy’ in appearance. • Uterine glands becomes engorged with glycogen during the phase following ovulation. • Endometrium is well prepared to accept and nourish an embryo . Uterine changes in the menstrual cycle. Endometrial depth More secretion from the glands – hence the term “secretory phase” Oestradiol causes an increase in thickness (the “proliferative phase”) 0 4 8 12 Menstruation 16 20 24 28 OVULATION The menstrual Phase • Occurs as a result of fall in ovarian hormone secretion during the late luteal phase . • Necrosis and sloughing of the stratum functionale may be produced by constriction of spiral arteries. • It seems spiral arteries are responsible for menstrual bleeding Terminal differentiation of stromal cells – “decidualisation” Characteristic “spiral arteries” 0 4 8 12 16 Menstruation 20 24 28 Optimal time for implantation Cyclic changes in the female reproductive tract • High levels of estradiol secretion cause cornification of vaginal epithelium. ( the upper cells die and become filled with keratin. • During luteal phase, high levels of progesterone cause the cervical mucus to thicken and become sticky after ovulation has occured. CLINICAL ABNORMAL MENSTRUATION : Most common disorders of female reproductive tract. • • • Amenorrhea: Absence of Menstruation. Dysmenorrhea : Painful menstruation which may be marked by severe cramping. Menorhagia: Excessively profuse or prolonged bleeding. Hormone involve in Pregnancy and Parturition Normal Pregnancy • Pregnancy The course that the embryo and the fetus grow in the maternal body • Stages of pregnancy Early pregnancy: ≤12 weeks Mid pregnancy: ≥13 weeks,≤27 weeks Late pregnancy:≥28 weeks Term pregnancy:≥37 weeks,<42 weeks Human Chorionic Gonadotropin Functions • Prevents degeneration of corpus luteum • Stimulates corpus luteum to secrete E + P which, in turn, stimulate continual growth of endometrium. • hCG stimulates leydig cells of male fetus to produce testosterone in conjunction with fetal pituitary gonadotrophins.Thus indirectly involved in development of external genitalia. • Suppresses maternal immune function & reduces possibility of fetus immunorejection • Stimulates maternal thyroid gland and development of fetal adrenal glands. Human Chorionic Somatomammotropin • effect on latation (HPL) ? •growth hormone effects •decreases insulin sensitivity - more glucose for the fetus • low levels - placental insuf. Estrogen (E) • FORMS-estriol,estradiol &estrone . • Estriol most important . • Levels increase throughout pregnancy • 90% produced by placenta.(syncytiotrophoblast) • Placental production is transferred to both maternal and fetal compartments • Main effects are: • Stimulate growth of the myometrium and antagonize the myometrial-suppressing activity of progesterone. In many species, the high levels of estrogen in late gestation induces myometrial oxytocin receptors, thereby preparing the uterus for parturition. • Stimulate mammary gland development. Estrogens are one in a battery of hormones necessary for both ductal and alveolar growth in the mammary gland. • Inhibition of Prolactin secretion Progesterone (P) • Levels increase throughout pregnancy • 80-90% is produced by placenta and secreted to both fetus and mother • • Progestins, including progesterone, have two major roles during pregnancy: Support of the endometrium to provide an environment conducive to fetal survival. If the endometrium is deprived of progestins, the pregnancy will inevitably be terminated. Suppression of contractility in uterine smooth muscle, which, if unchecked, would clearly be a disaster. This is often called the "progesterone block" on the myometrium. Toward the end of gestation, this myometrial-quieting effect is antagonized by rising levels of estrogens, thereby facilitating parturition. • • Progesterone and other progestins also potently inhibit secretion of the pituitary gonadotropins luteinizing hormone and follicle stimulating hormone. This effect almost always prevents ovulation from occurring during pregnancy • Stimulates development of alveolar tissue of the mammary gland Placental hormones: During early pregnancy, HCG is secreted by the syncitial trophoblasts. Later, the placenta secretes estradiol, progesterone, relaxin and somatomammotropin. Function of placental hormones: (summary) • • • • • HCG is similar to LH and maintains the corpus luteum in a functional state for 34 months. – This keeps progesterone levels high and they maintain the functional endometrium. Relaxin increases flexibility in the pelvic joints, as well as suppressing release of oxytocin. Placental progesterone keeps the uterine wall intact. Somatomammotropin acts like prolactin and triggers the mammary glands to develop. Estrogen increases the sensitivity of the myometrium to mechanical irritation, as well as oxytocin stimulation. Parturition Hormones and parturition • Stimulants – oxytocin – PGF2a – PGE2 • Relaxants – – – PGE2 relaxin -adrenergic nitric oxide • Endocrine – sex steroids, oxytocin • Paracrine – amnion-chorion-decidua-myometrium – sex steroids, oxytocin, prostaglandins, etc. • Autocrine – – – – – thrombin endothelin AT II a-adrenergic vasopressin Parturition • • • Parturition – Process by which a baby is born • Labor – In mother – – Estrogens overcome inhibitory influence of progesterone – Oxytocin is released First stage • Second stage • In fetus – Adrenal gland is enlarged prior – Onset of regular uterine contraction until cervix dilates to fetal head diameter From maximum cervical dilation until baby exits vagina Third stage • Expulsion of placenta from uterus • Estrogen in late pregnancy: – Stimulates production of oxytocin receptors in myometrium. – Produces receptors for prostaglandins. – Produces gap junctions between myometrium cells in uterus. • Factors responsible for initiation of labor are incompletely understood. Factors Influencing Parturition Regulators of Parturition Parturition: The Process of Childbirth • The mechanisms signaling the onset of labor are not clearly understood, although several theories exist. • Potential role of progesterone?: - decreasing progesterone prior to labor would allow uterine contractions to occur - however, there is no decline in progesterone before labor in humans - some studies suggest there is a decline in uterine progesterone receptors, resulting in decreased progesterone action, leading to labor Potential Role of Oxytocin in Parturition? • Oxytocin causes uterine contraction. • However, oxytocin levels do not increase until after labor starts, according to more recent studies. • Oxytocin may play a role in uterine contraction following labor, resulting in decreased blood loss. Potential Role of Relaxin in Parturition? • Relaxin acts on the cervix, causing dilatation and softening. • In some animals relaxin increases before labor starts. • In humans, relaxin is high beginning early in pregnancy and stays elevated until labor. • Relaxin does act to soften connective tissues, such as the ligaments connecting the pelvic bones, to allow increase in size of the birth canal. • Relaxin also decreases uterine contractility during pregnancy. Potential Role of Prostaglandins in Parturition Parturition (continued) • Prostaglandins cause dilation and softening of the cervix. • Prostaglandins also cause uterine contractions. • The levels of prostaglandins increase in fetal membranes before the onset of labor. • It is believed that some (unknown) signal from the fetus causes increased prostaglandin production from fetal membranes, which then act on the uterus and cervix to initiate labor. • Fetal adrenal cortex: – Chain of events may be set in motion through CRH production. – Fetal adrenal zone secretes DHEAS, which travel from fetus and placenta. • Uterine contractions: – Oxytocin. – Prostaglandins. Thank you for attention