2. Chapter Outline
• Duration of menstrual cycle
• Phases of menstrual cycle
- Follicular phase
- Luteal phase
• Changes in reproductive organs
• Changes in follicular phase
• Changes in luteal phase
• Strata of endometrium
• Mechanism of menstrual bleeding
• Hormonal changes in menstrual cycle
- Oestrogen
- Progesterone
- Luteinizing hormone
• Disorders of menstrual cycle
• Amenorrhoea
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
3. Introduction
• Reproductive system in females - pair of ovaries, uterine tubes, uterus, vagina
and external genitalia
• Fertile period - age of puberty to menopause
• Puberty - Period of adolescence in which a female reaches sexual
maturity and capable of reproduction
- Age : 11–14 years
• Menopause - Absence of menstrual cycle for a period of 12 months or more
- She is no longer able for reproduction
- Age: 49–52 years of age
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
4. • Fertile female - Monthly periodic changes in the ovary and uterus
from puberty till menopause
• Periodic changes - controlled by hormones of the pituitary gland
(hypothalamo–pituitary–ovarian axis)
• Periodic changes are grouped as follows:
Ovarian cycle
Uterine cycle or menstrual cycle
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
5. CHANGES IN FGT
OVARIAN CYCLE MENSTRUAL CYCLE
- Rhythmic changes in ovary
- Formation and maturation of ovarian follicles
- Release of gametes
- Secretion of ovarian hormones
- Periodic changes in endometrium
- Shedding of endometrium in absence of fertilisation
- Preparation of uterus for implantation
- Nourish fertilised gametes after implantation
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
6. Menstrual cycle
• Menstrual cycle - rhythmic change in uterus starting from puberty until
menopause.
• Menstruation - cyclic bleeding due to shedding of endometrium in the absence of
fertilization
• Menstrual cycle is studied as follows:
• Duration of cycle
• Phases of menstrual cycle
• Changes in reproductive organs
• Mechanism of menstrual bleeding
• Hormonal changes
• Disorders of menstrual cycle
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
7. Duration of Menstrual cycle
• “Menstrual” means lunar month of 28 days in Latin
• Average menstrual cycle : 28 days;
• Range : 21–35 days
• Menstrual cycle extends from the first day of beginning of the menstrual bleeding up to the first day of
beginning of the next menstrual bleeding
• Menstrual cycles are absent during pregnancy and lactation
• Factors affecting the duration of menstrual cycle:
Emotional status
Nutritional status
Psychological and social aspects
Environmental factors
Hormonal status
Near menopause
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
8. Phases of menstrual cycle
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
9. Menstrual phases
Follicular Phase (pre-ovulatory)
• Developing Ovarian follicle secrete
oestrogen
• Oestrogen controls changes in uterus
• Phases:
Menstrual phase – stratum
compactum, stratum spongiosum
shed off
Proliferative phase – uterine
endometrium proliferates
Luteal Phase (Post-ovulatory)
• Corpus luteum secretes
progesterone following ovulation
• Progesterone causes changes in
endometrium
• Phases:
Progestational phase: Changes in
endometrium due to progesterone
Secretory phase: uterus becomes
secretory
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
10. Phases of menstrual cycle
• Menstrual cycle
– follicular (post-menstrual) phase
– Proliferative phase
– Secretory phase and
– Menstrual phase
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
11. Endometruim
• Uterine endometrium - cyclic changes during menstrual cycle.
• Uterus three layers: (inside outwards)
Endometrium - inner mucous membrane/Functional layer of uterus
Myometrium - very thick and consists of smooth muscles.
Perimetrium - outer connective tissue layer covered by visceral peritoneum.
• Endometrium: columnar epithelium, connective tissue stroma and simple tubular uterine glands.
• Spiral arteries : Stroma of endometrium.
• Endometrium shows three strata :
Stratum compactum: Superficial layer containing necks of uterine glands.
Stratum spongiosum: Middle layer, consists of loose areolar tissue.
Stratum basale: Deep layer, lies adjacent to myometrium.
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
12. Endometruim
• Menstrual bleeding:
- Only stratum functionale (stratum compactum
and stratum spongiosum) shed off.
- Stratum basale do not shed off
• Stratum basale - fundi of uterine glands
• Stratum basale - straight arteries - branches of arcuate artery
• stratum spongiosum and compactum are supplied by spiral arteries.
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
13. Interesting facts
• Stratum functionale - stratum compactum + stratum spongiosum.
• Length of luteal phase remains constant (14 days)
Irrespective of length of the menstrual cycle, ovulation
takes place 14 days prior to next menstrual bleeding
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
14. Changes in reproductive system
• During menstrual cycle -
ovary and uterus show cyclic
changes specific to phases of
the cycle
• Follicular phase changes –
ovary, uterus
• Luteal phase changes – ovary,
uterus
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
15. • Ovarian cycle – one of the follicles reaches up to the stage of Graafian follicle.
• Primary oocyte – Mature and surrounded by follicular cells
– Forms primary, secondary and tertiary follicles
• Liquor folliculi – Separates follicular (granulosa) cells into inner cumulus oophoricus and outer stratum
granulosum.
• Stromal cells – (form) theca interna and theca externa.
• Granulosa cells – secrete oestrogen, influences uterine changes.
• Primary oocyte – completes first meiotic division
– Forms secondary oocyte and first polar body.
• At the end of follicular phase – secondary oocyte undergoes ovulation.
Changes in follicular phase – Ovarian changes
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
16. Menstrual phase
• Degeneration of corpus luteum at the end of the
previous menstrual cycle - stoppage of secretion of
progesterone and oestrogen.
• Absence of these hormones - temporary spasm
(contraction) of spiral arteries, results in ischemia
and necrosis of stratum compactum and
spongiosum (superficial 2/3rd of endometrium)
• Stratum basale has not been supplied by spiral
arteries (but by straight arteries) hence it does not
shed off
• Average duration: 3–5 days
• Menstrual blood does not clot due to the presence
of proteolytic enzymes
Proliferative phase
• 5th day onwards - under the influence of oestrogen,
the thickness of endometrium starts increasing due
to regeneration.
• Uterine endometrium undergoes hypertrophy and
hyperplasia.
• length of uterine gland increases
• Uterine glands become straight, long, widely
separated and they have scanty secretions
• Number of spiral arteries increases and it enhances
blood supply to the endometrium
• Under the influence of oestrogen, the volume,
alkalinity and elasticity of cervical mucous
increases. It makes cervical mucous favourable for
the passage of sperms through cervix of the uterus.
Changes in follicular phase – uterine changes
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
17. Changes in follicular phase – uterine changes
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
18. Changes in Luteal (progestational) phase- Ovarian changes
• Luteal phase starts after ovulation
• Ovulation : Ovarian follicle is filled with blood – corpus haemorrhagicus
• Granulosa cells start accumulating a yellow pigment (lutein), hence luteal phase.
This process is luteinisation of granulosa and theca cells
• Luteal cells secrete progesterone and oestrogen
• If fertilisation does not occur, then corpus luteum degenerate by the 26th or 28th
day
• Corpus luteum undergo luteolysis to form a scar tissue called corpus albicans
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
19. Changes in Luteal (progestational) phase- uterine
changes
• Changes in stroma :
- Spiral arteries become more tortuous.
- Vascularity of endometrium enhances.
- Uterine fluid starts accumulating in stroma and
makes it oedematous and thick.
- Stromal cells accumulate glycogen and lipid
droplets in their cytoplasm. This is called decidual
reaction
- Later part of the luteal phase, due to the
absence of progesterone, vasospasm of spiral
arteries begins to produce focal necrotic changes in
endometrium.
- At the end of the luteal phase: menstruation
begins in the absence of implantation
• Cervical mucus changes
- Progesterone:
cervical mucus becomes thick and less elastic.
These changes prevent entry of sperms
through cervix
• Changes in glands
- Uterine glands become more coiled and
tortuous (produces sawtooth appearance).
- Glandular epithelium starts accumulating
glycogen
- Glands secrete carbohydrate-rich fluid
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
20. Mechanism of Menstrual Bleeding
• Absence of pregnancy : Steroid hormone levels begin to fall due to the degeneration of corpus
luteum
• Decreased steroid hormone levels - increased coiling of spiral arteries and constriction,
result in decreased blood supply (ischemia) to endometrium
• Ischemia of endometrium: - Destabilisation of lysosomal membranes and release of
proteolytic enzymes from lysosomes
- Release of prostaglandins, mainly PGF2α.MCQ
• Loss of blood supply and action of proteolytic enzymes: Produce focal areas of necrosis, later
fuse form large necrotic areas in the endometrium
• Prostaglandins - Smooth muscle (myometrium) contractions, results into the beginning of
menstrual bleeding
• Presence of proteolytic enzymes - menstrual blood does not form clots
• Normal amount of menstrual bleed: 30–130 ml
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
21. Hormonal Changes in Menstrual Cycle
• Menstruation - influence of hypothalamo-
pituitary-ovarian axis (HPO axis)
• Pituitary gland secretes follicle stimulating
hormone (FSH) and luteinising hormone (LH)
• Ovaries : Produce oestrogen and progesterone
under the influence of the LH and FSH
• Secretion of LH and FSH by anterior pituitary is
under the control of gonadotropin-releasing
hormone (GnRH) of hypothalamus
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
22. Hormones in menstrual cycle
Endocrine gland Hormone Major functions
Anterior pituitary FSH
Stimulates follicular growth in ovaries.
Stimulates follicles for oestrogen secretion.
LH
LH surge causes ovulation.
LH surge, on ovulation, forms corpus luteum.
Ovaries Oestrogen
Stimulates endometrial proliferation.
Inhibits secretion of GnRH, FSH and LH.
Progesterone
Increases thickness of uterine endometrium and make it suitable
for implantation.
Inhibits GnRH, FSH and LH secretion.
Inhibin • Inhibits secretion of FSH by anterior pituitary.
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
23. • Amenorrhoea - Absence of menstrual cycle
• Hypomenorrhoea - Short or scanty periods (extremely light menstrual flow)
• Oligomenorrhoea - Infrequent menstruation that occurs at intervals of greater than
35 days (only 4–9 menstruations/year)
• Dysmenorrhoea - painful menstruation. It involves sharp, intermittent pain or dull
aching abdominal pain associated with the beginning of menstruation
• Premenstrual syndrome (PMS)
- non-specific symptoms that develop a week before onset of menstrual
bleeding
- Painful or swollen breast, depression, irritability, headache and so on
- Symptoms disappear 1–3 days after the menstruation starts
Disorders of Menstrual Cycle
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
24. Disorders of Menstrual Cycle
• Disorders of flow: amenorrhoea, hypomenorrhoea, oligomenorrhoea
• Painful menstruation: dysmenorrhoea, premenstrual syndrome
• Disorders of timing: menometrorrhagia, menorrhagia, metrorrhagia
• Disorders of ovulation: oligoovulation, anovulation
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
25. • Menorrhagia - Excessive menstrual bleeding
• Metrorrhagia - Uterine bleeding that occurs at irregular intervals
• Menometrorrhagia - Excessive uterine bleeding at frequent and
irregular intervals
• Anovulation - Absence of ovulation.
• Oligoovulation - Irregular ovulation, usually if menstrual cycle is more
than 36 days
• Polymenorrhoea - Frequent menstruation (cycle of less than 21 days)
Disorders of Menstrual Cycle
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
30. Ovulation
• Q. Write a short note on ovulation.
∙ Definition: Release of the ovum from the Graafian follicle.
∙ Time: 14 days prior to the onset of next menstrual bleeding. (MCQ)
• Responsible factors
1. LH surge: high concentration of luteinising hormone (LH) prior to the ovulation →
increase collagenase activity → digestion of collagen fibres surrounding follicle.
2. Prostaglandins: Increased concentration of prostaglandins → causes contraction of
smooth muscles of wall of the ovary.
3. Follicular fluid: Increased amount of follicular fluid → increased follicular pressure.
30
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
31. Ovulation
Events
High FSH level and LH surge
↓
↑ Increased follicular fluid
↓
Loosening of cumulus cells
↓
Formation of stigmata (avascular area) over the follicle
Digestion of collagen fibres surrounding follicle
↓
Rupture of follicle
↓
Shedding of secondary oocyte with corona radiata (cells of cumulus oophorous)
↓
Entry of ovum in fallopian tube 31
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
32. Box 2.3: Tests for ovulation
Tests for Ovulation (MCQ, Viva)
1. Calendar method: Ovulation occurs 14 days prior to the onset of next menstrual cycle.
2. Basal body temperature: Record the temperature every day in the morning.
Temperature ↓ 0.3°C–0.5°C just before ovulation and ↑ thereafter.
3. Cervical mucus method (Billings method): Watery and sticky at the time of ovulation
and it shows a fern pattern.
4. Hormonal estimation: ↑ LH and estrogen, ↓ FSH. Ovulation kits (ELISA strips like
pregnancy test kits) help for detection of LH surge.
5. Ultrasonography monitoring contributes to keep follow-up of ovulation.
6. Endometrial biopsy (nowadays it is not done routinely.)
32
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
33. Box 2.4: Disorders of ovulation
Disorders of ovulation(MCQ)
∙ Anovulation: Absence of ovulation. It may be due to menopausal or due to
hormonal imbalances.
∙ Oligoovulation: Infrequent or irregular ovulation.
∙ Induced ovulation: In assisted reproductive technology, clomiphene citrate and
a low dose of human chorionic gonadotropin are used for induced ovulation.
∙ Suppressed ovulation: Contraceptive hormonal pills suppressed folliculogenesis
and ovulation.
33
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
34. Structure of Ovum
Q. write a short note on the structure of ovum.
∙ Also called as a secondary oocyte.
∙ Size: 140 µm.
Structure: consists of a nucleus, ooplasm, vitelline
membrane, zona pellucida and corona radiata.
Nucleus
∙ Called germinal vesicle
∙ Contains 23,X chromosomes.(MCQ)
Ooplasm/ cytoplasm/ yolk
∙ Contains droplets of lecithin-like substances that
forms deutoplasm.(MCQ)
∙ Two centrioles are present near the nucleus but
they disappear during fertilisation.
34
Vitelline membrane
∙ Cell membrane that is surrounded by
perivitelline space.
∙ First polar body lies within perivitelline
space.
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35. Structure of Ovum
35
Zona pellucida:
∙ Glycoprotein coat that surrounds the vitelline membrane.
∙ Zona pellucida glycoprotein (ZP3) facilitates binding of sperms and induces an acrosomal
reaction. (MCQ)
∙ Prevents implantation. Zona pellucida disappears on 5th
-6th
day after fertilisation to permit
implantation. (MCQ, Viva)
Corona radiata
∙ Few cells of cumulus oophorous remain attached to the outer surface of the ovum and that
forms corona radiata.
∙ Acrosomal enzyme (hyaluronidase) disintegrates corona radiata cells during fertilisation.
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers
#3:Puberty is a period of adolescence in which a female reaches sexual maturity and becomes capable of reproduction. It occurs by the age of 11–14 years.
Menopause is the absence of menstrual cycle for a period of 12 months or more in the later life of a female and by then she is no longer able for reproduction. It occurs between 49–52 years of age.
#4:A fertile female shows monthly periodic changes in the ovary and uterus from puberty till menopause.
The periodic structural and functional changes of female reproductive organs are under the control of hormones of the pituitary gland (hypothalamo–pituitary–ovarian axis).
These periodic changes are grouped as follows:
Ovarian cycle: Rhythmic changes in the ovary involves formation and maturation of ovarian follicles, release of gamete (ovum) and secretion of ovarian hormones.
Uterine cycle or menstrual cycle: It consists of the periodic changes in the endometrium of uterus. It is mainly targeted towards the preparation of uterus for implantation, to nourish fertilised gametes after implantation and shedding of endometrium in absence of fertilisation.
#5:These periodic changes are grouped as follows:
Ovarian cycle: Rhythmic changes in the ovary involves formation and maturation of ovarian follicles, release of gamete (ovum) and secretion of ovarian hormones.
Uterine cycle or menstrual cycle: It consists of the periodic changes in the endometrium of uterus. It is mainly targeted towards the preparation of uterus for implantation, to nourish fertilised gametes after implantation and shedding of endometrium in absence of fertilisation
#6:Menstrual cycle is studied as follows:
Duration of cycle
Phases of menstrual cycle
Changes in reproductive organs
Mechanism of menstrual bleeding
Hormonal changes
Disorders of menstrual cycle
#7:Length of menstrual cycle varies from female to female. Even in one female, it is not always the same.
Usually, average menstrual cycle consists of 28 days. Menstrual means lunar month of 28 days in Latin (Flowchart 3.1, Figure 3.1).
Factors affecting the duration of menstrual cycle:
Emotional status
Nutritional status
Psychological and social aspects
Environmental factors
Hormonal status
Near menopause
The normal range of menstrual cycle: 21–35 days.
Each menstrual cycle extends from the first day of beginning of the menstrual bleeding up to the first day of beginning of the next menstrual bleeding.
Because of hormonal influence, menstrual cycles are absent during pregnancy and lactation
#9:Developing ovarian follicle secrete oestrogen that controls the changes in uterus. Hence, this phase of menstrual cycle is called follicular phase.
Follicular phase lasts up to ovulation.
In initial few days of follicular phase, superficial parts of the thickened endometrium (stratum compactum and stratum spongiosum) are shed off. It constitutes menstrual bleeding that lasts for 3–5 days. This part of follicular phase is also known as menstrual phase.
In remaining part of the follicular phase, uterine endometrium proliferates, hence called proliferative phase.
Following the ovulation, corpus luteum secretes progesterone that influences uterine changes. Hence, this phase is luteal phase or progestational phase.
Uterine endometrium becomes secretory in the luteal phase; hence, this phase is also called secretory phase.
#10:Menstrual cycle shows follicular (post-menstrual) phase, proliferative phase, secretory phase and menstrual phase (Flowchart 3.1).
In this chapter, menstrual cycle is divided into two phases: follicular phase (it includes menstrual phase) and luteal phase. These two phases are separated by ovulation