Overview Introduction Stages of menstrual cycle phase 1: follicular (proliferative) phase phase 2: mid-cycle or ovulation phase 3: luteal (secretory) phase phase 4: menses/pregnancy Events of menstrual cycle ovarian follicle and oocyte develop reproductive tract prepares to receive fertilized ovum endometrial lining sheds if fertilization fails Menstrual cycle length menstrual cycle averages 28 days, but varies from 28 days to 35 days variability in cycle length is attributed to follicular (proliferative) phase luteal (secretory) phase is constant (14 days) ovulation day + 14 days = menstruation Phase 1: Follicular/Proliferative Phase (Day 0 - Day 13) Folliculogenesis overview folliculogenesis is the process by which primordial follicles develop into a single mature, dominant Graafian follicle it is controled by the hypothalamic-pituitary axis GnRH → ↑ FSH → (+) folliculogenesis growth of follicles is fastest during week 2 of follicular (proliferative) phase follicular (proliferative) phase varies in length Stage of folliculogenesis stage 1: primordial follicle → primary follicle GnRH → ↑ FSH → (+) primordial follicle → primary follicle a primordial follicle consists of a primary oocyte surrounded by a single layer of squamous pre-granulosa cells 15-20 primordial follicles develop into 15-20 primary follicles a primary follicle consists of a primary oocyte surrounded by a single layer of cuboidal granulosa cells granulosa cells acquire FSH receptors granulosa cells secrete layer of glycoproteins on surface of primary oocyte zona pellucida stage 2: primary follicle → secondary follicle GnRH → ↑ FSH → (+) primary follicle → secondary follicle primary follicles develop into secondary follicles a secondary follicle consists of a primary oocyte surrounded by several layers of cuboidal granulosa cells as the secondary follicle develops, stromal cells differentiate to form theca cells theca cells acquire LH receptors basement membrane separates theca cells and granulosa cells stage 3: secondary follicle → tertiary follicle → graafian follicle GnRH → ↑ FSH and ↑ LH → ↑ 17β-estradiol (major) and ↑ progesterone (minor) 17β-estradiol prepares uterus for embryo implantation causes proliferation of endometrium negative feedback mechanism ↑ 17β-estradiol → (-) anterior pituitary → ↓ FSH and ↓ LH secondary follicles develop into tertiary ("antral") follicles granulosa cells increase in number and in size granulosa cells secrete fluid into center of follicles, creating a fluid-filled center a tertiary ("antral") follicle contains a fluid-filled space or antrum antrum enlarges and surrounds primary oocyte a mature, pre-ovulatory follicle is called a Graafian follicle stage 4: Graafian follicle development a single, mature Graafian follicle will rupture and release oocyte during ovulation other follicles in initial pool of 15-20 primordial follicles will undergo atresia immediately prior to ovulation, primary oocyte completes meiosis I yielding secondary oocyte and the first polar body Phase 2: Mid-Cycle or Ovulation (Day 14) Hypothalamic-pituitary axis positive feeback mechanism ↑↑ 17β-estradiol → (+) anterior pituitary → ↑↑ FSH and ↑↑ LH LH surge rising levels of estradiol triggers LH surge, triggering ovulation ovulation Graafian follicle ruptures and releases secondary oocyte into peritoneal cavity secondary oocyte is picked up by fimbriae of Fallopian tube and is transported through infundibulum into ampulla by means of ciliary movement of tubal epithelium and muscular contractions of tube Phase 3: Luteal or Secretory Phase (Day 15 - Day 28) Hypothalamic-pituitary axis LH Surge ↑↑ LH → (+) theca cells → ↑ progesterone (major) and ↑ 17β-estradiol (minor) post-ovulation "surge" drives development of corpus luteum corpus luteum is composed of residual elements of ruptured Graafian follicle includes granulosa cells and theca cells corpus luteum synthesizes and secretes progesterone and 17β-estradiol progesterone maintains endometrium to support embryo implantation progesterone increases hypothalamic-set point raises basal body temperature Phase 4: Menses/Pregnancy Menses corpus luteum regresses and is replaced by a fibrotic scar (corpus albicans) regression causes abrupt loss of progesterone and 17β-estradiol endometrial lining sloughs, causing menstrual bleeding Pregnancy if fertilization occurs, syncytiotrophoblasts secrete hCG that "rescues" corpus luteum corpus luteum continues to synthesize/secrete progesterone and 17β-estradiol Pathology of Menstrual Cycle Oligomenorrhea menstrual cycles occurring at intervals > 35 days Polymenorrhea menstrual cycles occurring at intervals < 21 days Metrorrhagia menstrual cycles occurring at irregular intervals inter-menstrual bleeding Menometrorrhagia menstrual cycles occurring at irregular, more frequent intervals heavy menstrual bleeding