Histology and pathology of menstrual cycle Flashcards
Define the menstrual cycle
- Monthly cyclical changes in secretion of female hormones, with corresponding changes in ovaries, uterus, and other sexual organs.
- During reproductive years of females: menarche to menopause.
- The cycle results in:
- Ovulation
- Preparation of the uterus for implantation
- Menstruation
- Approximately 28 days (21-35)
Describe the stages of a normal menstrual cycle
Normal Cycle
First meiotic division occurs in embryogenesis.
500000 primordial follicles at birth in each ovary waiting for second meiotic division.
Meiosis II follows sperm entry.
Cyclic changes in the ovary and uterus
-
Ovarian cycle: production of ovarian hormones and the release of a mature ovum
- Follicular phase (before ovulation, days 1-14) and luteal phase (after ovulation, 14-28)
-
Endometrial cycle: preparation for implantation; menses
- Menstrual phase (day 1-5)
- proliferative phase before ovulation;
- Secretory phase post-ovulation.
Note that the first half of the cycle is more variable between women, most women then have predictable 14 days after ovulation i.e. before menstruation.
Describe uterus
- Uterus : comprised of fundus, body and cervix
-
Endometrium:
- Glands (tubular, simple columnar epithelium) surrounded by specialised endometrial stroma (special fibroblasts which are hormone-responsive)
- mucosal lining of uterus
-
Myometrium:
- Smooth muscle thickness of uterine wall: bundles of smooth muscle fibres with pencil-shaped elongated nuclei, pink cytoplasm due to actin fragments, plentiful mitochondria, bundles of muscles intersect at right angles
-
Endometrium:
Describe ovary - cell types
- ovarian stroma: developing oocytes and follicles at different stages of development
- sex chord stromal cells: granulosa cells with more rounded nuclei and theca cells with more ovoid or spindled nuclei
- oocyte: largest human cell, nucleus and enormous cytoplasm
- graafian/mature follicle: oocyte is only one cell, within follicle
- antrum: oestrogen/progesterone-rich fluid making up majority of follicle
List and describe the hormones involved
-
Hypothalamus
- Gonadotropin-Releasing Hormone (GnRH)
-
Anterior Pituitary
- Gonadotropic hormones:
- Follicle-Stimulating Hormone (FSH)
- Luteinising Hormone (LH)
- Gonadotropic hormones:
- Ovaries - elicit negative feedback to suppress GnRH, FSH and LH, for most of cycle, but positive feedback just before ovulation
- granulosa and theca cells produce oestrogen and progesterone
- Oestrogen: immediately prior to ovulation, very high peak in estradiol has positive feedback effect, resulting in mid-cycle LH surge and ovulation. For rest of cycle estradiol and progesterone suppress FSH and LH
- Progesterone
Describe the HPO axis
- GnRH: pulsatile release every 60-90 mins, with corresponding release of LH and FSH
- FSH and LH stimulate growth of ovarian follicles, and subsequent release of ovarian hormones (oestrogen and progesterone)
- Ovarian hormones elicit negative feedback (suppressing GnRH, FSH and LH) for most of the cycle, but positive feedback just before ovulation
Describe the feedback effect of oestrogen
- Immediately prior to ovulation, the very high peak in oestradiol has a positive feedback effect, resulting in a mid-cycle LH surge, and ovulation.
- For the rest of the cycle, oestradiol (and progesterone) have a negative feedback effect, causing suppression of LH and FSH release
Describe the follicular phase and luteal phase in terms of the hormones involved
Ovarian Cycle: Follicular Phase
- FSH → follicle growth
- Growing follicles produce oestrogen (oestradiol)
- Peak in oestrogen triggers LH release
- LH stimulates ovulation
LH stimulates ovulation
Ovary: Follicular Phase (day 5-14)
- FSH → accelerated growth of primary follicles
- Primary follicles produce oestrogen
- Oestrogen increases follicular expression of FSH receptors → growth
- FSH & Oestrogen cause an increase in LH receptors → increasing sensitivity to LH
- Oestrogen peak above the threshold stimulates LH release
- LH surge stimulates final follicular growth and ovulation (day 14)
Ovulation – day 14
- LH surge triggers ovulation
- Follicular capsule ruptures (action of enzymes and prostaglandin); ovum is released
- Remaining follicular capsule = corpus luteum
- Basal body temperature rises
- Some females experience mid-cycle “Mittelsmertsch” = Ovulation Pain
Ovary: Luteal Phase (day 14-28)
1. Remaining cells of ruptured follicle become corpus luteum
2. Corpus luteum produces progesterone (and some oestrogen) to prepare endometrium for implantation, inhibiting further FSH production
3. Very important to support forst 8 weeks of pregnancy, failure can lead to loss of pregnancy in some pateitns
Ovary: Luteal Phase (day 14-28)
- If ovum not fertilised
- Corpus luteum degenerates = progesterone production ceases
- Uterine wall sloughed off (menses)
- FSH production resumes
What happens to the polar body?
- haploid cell formed during meiotic division
- incapable of fertilisation
- small with little cytoplasm
- undergoes apoptosis
Describe the actions of oestrogen
Oestrogen:
- Greatest effect 1st half of the cycle
- Causes marked proliferation of:
- Endometrial stroma
- Endometrial glands which later provide sustain the fertilised ovum
Other effects of Oestrogen:
- External female sex organs: maturation at puberty; pubic hair
- Fallopian tubes: increases the number of, and motility of cilia
- Breasts: growth of ducts and stroma; fat deposition
- Skeleton: inhibits bone break-down; stimulates bone growth; epiphyseal fusion
- Skin: softer, more vascular
Describe the actions of progesterone
Progesterone:
- Greatest effect 2nd half of the cycle
- Promotes secretory changes in the endometrium:
- Prepares the uterus for implantation
- Nourishes the fertilised ovum - Inhibits FSH production
- Prevents other follicles from developing
Other effects of Progesterone:
- Uterus: Decreases frequency/intensity of uterine contractions (prevents expulsion of implanted ovum)
- Fallopian tubes: promotes secretions necessary for nutrition and movement of fertilized ovum within the tube.
- Breasts: promotes development of lobules and alveoli, causing swelling
Why is balance of oestrogen and progesterone important?
GENERALLY NOT GOOD TO HAVE UNAPPOSED (X.S) OESTROGEN AS THIS CAN RESULT IN ENDOMETRIAL HYPERPLASIA AND EVENTUALLY ENDOMETRIAL CARCINOMA
- Too much/too little of either can cause:
- Infertility (contraception)
- Dysfunctional Uterine Bleeding
BALANCE IS IMPORTANT
- OESTROGEN
- Proliferation
- PROGESTERONE
- Secretion
- Inhibition of proliferation
Describe the proliferative phase and ovulation
-
Proliferative Phase (day 5-14) = REGENERATION
- Endometrium is desquamated at menstruation, leaving only a thin layer of basal regenerative layer
- Increasing oestrogen (from ovarian follicles) → stromal and epithelial proliferation with gland and blood vessel formation
- Glands produce mucus which lines the cervical canal
Endometrium: Proliferative Phase (day 5-14)
Early proliferative phase. Thin layer of epithelium, small glands
- Increasing vascularity, proliferation of epithelium and stroma, glands more tortuous under the influence of oestrogen
- Mitosis visible as dark purple nuclei – indicates proliferation of cells
- Purpose: TO REBUILD LOST ENDOMETRIUM
- Tubular, non-secretory glands
- Progressively coiled
- Cellular endometrial stroma
- Progressively oedematous
- Mitotic activity in glands and stroma
- Disappears by ovulation
Ovulation
- Following ovulation (Day 14), endometrium prepares for implantation
- It begins to secrete a nutrient-rich substance in preparation for fertilised ovum
- Early sign of ovulation in epithelium is sub-nuclear vacuolisation 2-3 days post ovulation
- These vacuoles migrate to the luminal surface of cells and are secreted
**Day 16-17 (2-3 days post ovulation)
- Sub-nuclear vacuolisation: Beginning of secretory phase, a nutrient-rich substance forms in epithelium that will be secreted into the lumen to nourish fertilised ovum
- Sub-nuclear vacuolisation is a sign that ovulation has occurred
- Ovulation = Piano Keys!
Describe secretory phase
Purpose: nourish implanted blastocyst until placentation is complete in
response to progesterone
* Blastocyst munches on glandular secretions and swollen endometrial
stromal glands filled with nutrients
- Progesterone and oestrogen (from corpus luteum) → continued cellular proliferation; endometrium (glands and stroma) measures up to 5-6mm thick
- The cells are rich in glycogen and lipid
- Blood vessels and glands become more tortuous
- Trophoblastic cells on the surface of the fertilised ovum digest endometrium, absorbing stored nutrients
- Near constant 14 day length between women
- Accurate dating possible histologically (i.e., POD Post-ovulatory day 1,2,3 e.t.c)
- Purpose: TO NOURISH IMPLANTED BLASTOCYST UNTIL PLACENTATION IS COMPLETE
- The blastocyst munches on glandular secretions and gobbles up swollen endometrial stromal cells filled with nutrients!
- Absence of mitotic activity
- Glands are tortuous (wiggly) and show secretion
- Subnuclear vacuoles ➔supranuclear vacuoles ➔discharge mucous into lumen ➔secretions disappear (“secretory exhaustion”)
- Endometrial stromal cells progressively swell with nutrients (“pseudodecidua”)
- (“decidua” = endometrium of pregnancy)
- Spiral arterioles
- Progressively spiral/visible toward the end of the cycle, eventually spasm causing ischemic sloughing
What is the role of decidua?
- Arias stella reaction shows hypersecretory glands and decidualised stroma (plump nutrient rich stromal cells)
- Pregnancy is an exaggerated secretory phase endometrium caused by high levels of progesterone secreted from the Long-lived corpus luteum of pregnancy!
