2110571

Sharimilee a/p Ratnam

Definition: regular cyclical changes occurring in
females of child bearing age characterized by periodic
vaginal bleeding

Usual length; 28 days (may vary according to
individual and external factors)
If unusual?
Made up of 2 cycles
Ovarian cycle
Uterine cycle

Ovarian Cycle
3 stages
Folicular phase (dominated
by maturing follicle)
Ovulation (release of the
secondary oocyte)
Luteal / Secretory phase (in
uterus) (characterised by the
presence of corpus luteum)
Fetal life; even before we ladies are born, weve already got meiosis up and
running.

The primordial germ cells, a.k.a the Oogonia start to undergo meiosis, but
unfortunately, they dont complete it. (meiotic arrest..) These half
cooked oocytes remain this way up to puberty. We call them
Primary
oocytes
Diploid 46
chromosome
Surrounded
by granulosa
cells
Single layer of granulosa cells proliferate to form several layers that surround the
oocyte

These granulosa cells themselves make the zona pellucida as a membrane that
separate themselves from the oocyte.

The zona pellucida has gap junctions through which the granulosa cells supply ions
and small molecules to the oocyte (akin to how the sertoli cell nurses the
developing sperm)
Granulosa cells also release paracrines that form an
outer layer known as the Theca cells.

Granulosa cells + Theca cells = FOLLICULAR CELLS
(whose main function is estrogen secretion)


So now that the follicular cells have start
secreting stuff, all of its secretion has to
go somewhere, right?

A fluid filled cavity (antrum) forms in
the middle of the granulosa cells. Fluid
is made up of secretions of the follicular
cells (eg. Estrogen).

The antral follicle undergoes rapid
growth. (more estrogen produced more
growth,)

During each cycle 15-20 primary follicles mature, but only one dominant follicle will
fully mature.

Greatly expanded antrum pushes oocyte (which has developed in to 2ndry oocyte) to
one side of the growing follicle. The greatly expanded mature follicle bulges on the
ovarian surface, creating a thin surface that ruptures to release the oocyte at ovulation.

Release of ovum is triggered by LH SURGE

Rupture follicle develops into corpus luteum via
process called luteinization whereby cells enlarge and
are converted to active steroid hormone producing
tissue
Contains an abundance on cholesterol (steroid
hormone precursor) which gives its yellow colour

Highly vascularised to enable secretion of high amouts
of progesterone and smaller amounts of estrogen it
blood.
Human ovary with fully developed
Corpus Luteum
Ovum
Fertilised within 14d
Corpus luteum continues to grow and
produce increasing quatities of
progesterone and estrogen until
development of placenta.
Not fertilised
Luteal cells degenerate and are
phagocytosed .Connective tissue
rapidly fills to form corpus
albicans (white body)
Follicular Phase
FSH; antrum formation
LH + FSH; proliferation of granulosa
cells
LH; theca cells to produce
androgens
FSH; granulosa cells to produce
enzyme aromatase to convert
androgen to estrogen
Thus, rate of estrogen production
depends primarily on circulating LH
levels.
So what happens to the estrogen
secreted?
Partly enters blood (to supply sex-
specific organs e.g. uterus), while the
rest remains in antrum, further
stimulating growth of granulosa cell.

Further growth of granulosa cells, more
estrogen produced.

Estrogen also has negative feedback on
hypothalamus in NEGATIVE
FEEDBACK MECHANISM, resulting in
reduced GnRH-prompted released


Secretion of inhibin by follicular cell also contributes to fall in FSH. Decline in FSH
results in atresia of all but the single most mature follicle. (Sort of like survival of the
fittest)

Estrogen alone cannot inhibit tonic secretion of LH because both estrogen and
progesterone is needed. At this stage, progesterone secretion hasnt started yet. Thus, LH
levels slowly increases.
If there is a negative feedback mechanism, why only
FSH is reduced while LH continues to rise?
Ovulation
LH is secreted in two modes
Tonic secretion partially suppressed by inhibitory
action of estrogen during follicular phase and
completely suppressed by progesterone in luteal phase.
(NEGATIVE FEEDBACK EFFECT)
LH surge triggered by POSITIVE FEEDBACK where peak levels of
estrogen, instead if inhibiting, now acts directly on hypothalamus to
INCREASE GnRH, thus, both FSH and LH levels increase. However, FSH
does not increase as much as LH because continued inhibin secretion
keeps it low.

The amount of estrogen required to trigger an LH surge can only be
produced by a mature follicle. This way, it can be made sure that follicle will
only be ovulated when it has reached the proper degree of maturation

Process of ovulation in women 45 years old canada,
taken by a doctor named Dr Donnez, from the Catholic
University of Louvain, using a small camera-shaped tube
Result of LH surge
Halts estrogen synthesis
Reinitiates mitosis by blocking oocyte
maturation-inhibiting factor
Trigger production of local prostaglandins to
promote vascular changes to cause rapid
follicular swelling, resulting in swelling
which would eventually lead to rupture of
ovarian wall a.k.a ovulation
Cause differentiation of follicular cell into
luteal cell
Luteal Phase
Under influence of LH, corpus luteum secretes both
estrogen and progesterone (more abundant).

Estrogen level climbs again, but not as much as it
did in the follicular phase. Progesterone prevents
estrogen from trigerring another LH surge by
powerfully inhibiting LH itself, and FSH too.

No inhibin released, as progesterone is adequate to
inhibit FSH so that preparation to receive fertilised
ovum is carried out instead of preparation of other
ova for release.
Corpus luteum does its job for about
2 weeks; if still no fertilisation,
degenerates. But how?

LH influences corpus luteum to
release progesterone which in turn,
inhibits LH itself. Eventually, no LH,
no stimulation of corpus luteum, no
more progesterone, no more
inhibition on LH and FSH

Cycle repeats all over again.
Uterine Cycle
Influence of Estrogen and Progesterone on
the two layers of the uterus
Myometium: outer smooth muscle layer
Endometrium: inner lining containing
numerous blood vessels and gland

Estrogen stimulate growth of both
myometrium and endometrium, induces
synthesis of progesterone receptors in the
endometrium

Progesterone makes endometrial tissue
loose and edematous to facilitate
implantation, secrete and store glycogen ,
growth of endometrial blood vessels
Menstrual Phase
Characterised by discharge of blood
and endometrial debris from the
vagina

First day of menstuation is the day 1
of cycle

No fertilisation degeneration of
corpus luteum drop in
progesterone and estrogen levels
deprive uterine lining of its
hormonal support death of
endometrium

Fall in ovarian hormone levels uterine prostaglandin release
vasoconstriction of endometrial vessels reduction in O2 supply
death of endometrium

Uterine prostaglandin release rhythmic contraction of uterine
myometrium expulsion of blood and endometrial debris from
uterine cavity

Excessive uterine contraction; dysmenorrhea (menstrual cramps)

Average blood loss in a single menstrual period is 50-
150 ml

Lasts 5-7 days

After 5-7 days, FSH and LH from newly growing
follicles secrete enough estrogen to induce repair and
growth of endometrium

Proliferative phase
Endometrium starts to repair itself and proliferate
under influence of estrogen from newly developing
follicles
Secretory phase
Coincides with ovarian luteal phase

Large amounts of progesterone from corpus luteum
converts endometrium to richly vascularised, glycogen
filled tissue

Secretory; because endometrial glands are actively
secreting glycogen into uterine lumen for nourishment
of developing embryo.