Download Physiology of Reproduction

Physiology of
Women Reproduction System
Introduction of the internal reproductive
organs
• The vagina is a muscular canal, which leads from the uterus
to the valva
• the uterus is a hollow, smooth-muscled organ. It is lined by a
glandular epithelium, the endometrium. It is related to
menstruation.
• The fallopian or uterine tubes
each fallopian tube extends
outwards from the uterine cornu to end near the ovary. The
tubes, or oviducts, convey the ovum from the ovary towards
the uterus, providing oxygenation and nutrition for sperm,
ovum and zygote,should fertilization occur.
• The ovaries are two almond-shaped solid organs, measuring
about 3.5cm in length, 2cm in depth and 1cm in thickenss.
Whole life of women’s
• Neonatal period within four weeks after birth
• childhood from after four weeks to less than 10
years old
• puberty
• sexual maturity (reproductive years, childbearing
years) from 18
• perimenopausal period round 50 years old
• Senility more than 65
Menstruation and its clinical features
1. menstruation: defined as uterine bleeding in a
regular, recurring and predictable occurs once a
month .menstruation is established at puberty
(around age 13) and continues until the time of
menopause at around age 50 .Thus a woman has
approximately 30～40 years of reproductive
function.
2. menarche:
menstruation first occurs. This is the most
definite sign that puberty has commenced. Over the last 100
years. the average age of the menarche has steadily declined
from age of 14～16 years to 11～15 years. This changes is
probably related to better nutrition and increased body
weight in adolescents . Conversely the menarche is delayed in
girls suffering from malnutrition. The age of the menarche is
not related to climate. The onset of menstruation does not
directly equate with the onset of fertility as the early
menstrual cycles in adolescents are often anovular.
3. menstrual cycle: The length of a menstrual cycle
is counted in days from the first day of bleeding to
the first day of next cycle. The length of the normal
cycle varies from woman to woman and from time
to time in the same woman. The 1st day of
menstruation is considered day 1 of the menstrual
cycle .The average duration of a menstrual cycle is
28～30 days. but variations of 21～35 days are
accepted as within normal limits. Cycles shorter or
longer than this are more likely to be anovulatory.
4. menstrual period: The duration of the
menstrual flow is very variable ,the average is
3～5 days, durations of 1～8 days can be normal.
The amount of menstrual flow peaks on the first
or second day of menstruation. The amount of
blood loss during menstruation is approximately
30～50ml. ranged from 20～80ml, more than
80ml is considered menorrhagia.
5. menstrual flow consists of nonclotting
blood ,mucus，cellular debris and endometrium
fragments.
The menstrual flow is usually scanty and viscid
at first, later becoming bright red, and finally
brown towards the end of the period. Small clots
and fragment of endometrium may be seen, but
large clots are only passed when the bleeding is
excessive.
• Symptoms of menstrual period: There may be
abdominal discomfort, headache, soreness of
breasts, feeling of tired etc .Usually these
symptoms are not severe.
• The most obvious manifestation of the normal
menstrual cycle is the presence of regular menstrual
periods. These occur as the endometrium is shed
following failure of implantation or fertilization of the
oocyte.
• Why women have recurring，regular menstrual cycle?
• The menstrual cycle depends on the cyclic interaction
between
hypothalamic
Hormone(GnRH),the
pituitary
gonadotropin–releasing
gonadotropins
follicle–
stimulating hormone (FSH) and luteinizing hormone
(LH),and the ovarian sex steroid hormones estradiol and
progesterone .Through positive and negative feedback
loops, these hormones stimulate ovulation, and bring about
menstruation .If any one (or more ) of the above hormones
becomes elevated or suppressed, the menstruation cycle
will becomes disorder ,or ovulation and menstruation cease.
Hypothalamic GnRH secretion
• The hypothalamus ,via the pulsatile secretion of GnRH, stimulates
pituitary LH and FSH secretion.
GnRH is a decapeptide hormone , it is secreted in a pulsatile
manner from the arcuate nucleus of the hypothalamus. The mechanism
for stimulation of GnRH secretions is unknown. however, GnRH
secretion is influenced by estradiol and catecholamine etc
neurotransmitters. GnRH reaches the anterior pituitary gland through
the hypothalamic –pituitary portal plexus. Pituitary gonadotropin
secretion is stimulated and regulated by the pulsatile secretion of GnRH.
Pituitary gonadotropin secretion
• The pituitary gonadotropins FSH and LH are protein hormones
secreted by the anterior pituitary gland. FSH and LH are also
secreted in pulsatile fashion in concert with the pulsatile release of
GnRH, the quantity of secretion and the rates of FSH/LH are
determined largely by the levels of ovarian steroid hormones and
other ovarian factors .When a woman is in a state of relative
estrogen deficiency, the principal gonadotropin secreted is FSH.
FSH stimulates the follicular development, maturation and the
production of estrogen. LH induces ovulation of mature follicle,
corpus lutein formation and the production of progesterone and
estrogen.
H-P-O axis
hypothalamic --------------GnRH
Pituitary -----------gonadotropin (FSH,LH)
ovary---------- sex steroid hormone
Uterus and other organs
Ovarian functions and its cyclic changes
Ovarian functions
1. Reproductive function: provides oocyte monthly.
2. Endocrine function: produces steroid hormones during the follicle
grows.
• Within the ovary, the menstrual cycle can be divided into three
phases:
the follicular phase
ovulation
the luteal phase
•
menstrual cycle
Menstruation follicular phase
Sheding of
endometruim
Premordial
development
of follicles
preantral
ovulation
escape
of oocyte
antral
luteal phase
formation of
corpus luteum
Preovulatory
Or mature
Ovarian Cyclic Changes
1. Development and maturation of follicle (the follicular phase
in the menstrual cycle )
The ovary contains thousands of the primordial follicles. Follicles
first form in the female fetus during the fourth month of pregnancy ,
these primordial follicles are the smallest ，about 50μm in diameter,
and about 7 million are formed initially. At birth, their number has
declined to about 2 million.
Each primordial follicle contains an oocyte, surrounded by a single
layer of pregranulosa cells.(see Fig.)
The development of the oocyte is the key event in the follicular phase of the
menstrual cycle.
Development beyond the preantral stage is stimulated by
the pituitary hormones,LH and FSH,which can be considered
as key regulators of oocyte development.
•
at the start of the menstrual cycle, FSH levels begin to rise
as the pituitary is released from the negative feedback effects
of progesterone, oestrogen. Rising FSH levels rescue a cohort
of follicles from atresia, and initiate steroidogenesis.
• After puberty, a constant small proportion of follicles start
growing each day but only about 400 will ever release a mature
oocyte, a far greater number never mature and finally undergo
atresia.
• As a primordial follicle is stimulated by FSH ，the oocyte enlarges,
surrounded by a membrane, the zona pellucida; pregranulosa cells
become granulosa cells，which begin proliferation and secreting
estradiol; the stroma surrounding the granulosa cells begin to
organize the thecal layer, which secrete androgens. These follicles
are named preantral follicle, about 200 μm in diameter.
Under the synergistic influence of estrogen and FSH
there is a concomitant increase in the production of
follicular fluid, which accumulates in the intercellular
spaces of the granulosa to form a cavity, this stages of
follicle is called antral follicle (or developing follicle ),
about 500μm in diameter, granulosea proliferate to
become multilayer, the theca is broadly divided into
two layer; theca folliculi internal and theca folliculi
external.
During a full reproductive cycle, one oocyte is
brought to maturity before ovulation. In the process
of bringing one oocyte to maturation, a number of
oocytes are stimulated to partial maturation but
subsequently undergo atresia before reaching
ovulation. one of ripe follicles ruptures at about day
14 of each menstrual cycle to discharge its oocyte.
the follicles which rupture are converted into a
corpus luteum, which eventually retrogresses and
becomes a corpus albicans.
•
• Steroidgenesis
•
The basis of hormonal activity in preantral to preovulatory
follicles is described as the “two cell, two gonadotrophin”
hypothesis.steroidogenesis is compartmentalized in the two cell
types whthin the follicle: the theca and granulosa cells. The two
cell, two gonadotrophin hypothesis states that these cells are
responsive to the gonadotrophins, LH and FSH respectively.
•
Within the theca cells, LH stimulates the production of
androgens from cholesterol. Within granulosa cells, FSH
stimulates the conversion of thecallyderived androgens to
oestrogens(aromatization). In addition to its effects on
aromatization, FSH is also responsible for proliferation of
granulosa cells.
•
• Ovarian steroidogenesis.the ovary has the capacity to synthesize
oestradiol from cholesterol. The major products of the ovary are
oestradiol and progesterone although small amounts of
testosterone and androstenedione are also produced. See Fig.
• Dominant follicle
the developing follicle grows and produces steroid
hormones under the influence of the gonadotrophins LH
and FSH. These gonadotrophins rescue a cohort of prantral
follicles from atresia. However, normally only one of these
follicles is destined to grow to a preovulatory follicle and
be released at ovulation-the dominant follicle.
the dominant follicle is the largest and most developed
follicle in the ovary at the mid-follicular phase. Such a
follicle has the most efficent aromatase activity and the
highest concentration of FSH-induced LH receptors.
for various causes the largest follicle requires the
lowest levels of FSH(and LH) for continued development.
• In a lot of developing follicle ,only one leading follicle
(dominant follicle) can reach maturation (≥20mm in
diameter ) and ovulation during a menstrual cycle, It is
called mature follicle (or preovulatory follicle ).The
cavity of mature follicle enlarge, follicular fluid
increase, oocyte is pushed to one side of follicle, follicle
moved towards the surface of ovary .
• The phase of follicle development , from primordial to
mature ,is called follicular phase .
2. Ovulation
The process during which a mature follicle ruptures to
release a mature oocyte with some granulosa cells and
follicular fluid .The mechanism for ovulation is not very clear,
LH surge is necessary for ovulation, it precipitates the final
maturation of follicle, changes in the follicular wall and
follicular fluid volume. LH surge also increase production of
intrafollicular prostaglandins which play an essential role in
release of the oocyte, the administration of prostaglandin
synthetase inhibitors will cause the oocyte to be retained
within the follicle during the luteal phase of the cycle.
• In addition. some enzymes play a role for ovulation. In
humans spontaneous ovulation usually occurs 24～36h
after the LH surge.
• Ovulation usually occurs 14 days before the next
expected menstruation, i. e. around at day 14 in a 28
days cycle .In longer cycles ovulation occurs later, i.e.
around day 19 in a 33days cycle. In many women,
ovulation may be associated abdominal discomfort or
pain.
3. Formation and degeneration of corpus luteum
( luteal phase in the menstrual cycle)
After ovulation follicle collapsed, original granulosa cells enlarge,
accumulating yellow lipid, called granulosa corpus lutein cells ,
meanwhile theca cells become theca corpus lutein cells, right now, corpus
luteum formed .
the luteal phase is characterized by the production of progesterone
from the corpus luteum within the ovary.
About 7～8 days after ovulation， the corpus lutein development reach
maturation,2～3cm in diameter ,at the time the corpus leteum secretes
maximal estrogen and progesterone . The production of progesfterone
from the corpus luteum is dependent on continued pituitary LH secretion.
•
If fertilization and implantation do not occur, at 9～10 days
after ovulation the corpus luteum begins degeneration ,it
decreases in volume and loses its yellow color ,hormones
production diminishes rapidly ,cells denatured ,menstruation
ensues leading to the beginning of a new cycle .
The corpus luteum has a fixed life period, about 13～14
days unless pregnancy occurs .If the oocyte becomes fertilized
and implants within the endometrium, the early pregnancy
begins secreting human chorionic gonadotropin (HCG),which
support the corpus luteum for another 6～7 weeks. If there
has been no pregnancy, after 8～10 weeks the corpus luteum
becomes a white fibrous streak within the ovary called the
corpus albicans .The phase from formation to degeneration of
corpus luteum called luteal phase.
If there has been no pregnancy, after 8～10
weeks the corpus luteum becomes a white
fibrous streak within the ovary called the
corpus albicans .The phase from formation to
degeneration of corpus luteum called luteal
phase. However, serum levels of progesterone are such
that LH and FSH production is relatively suppressed.
So a menstrual cycle is divided into follicular
phase，Ovulation phase and luteal phase .
Sex steroid hormones secretion in ovaries
The ovaries secrete estrogen (E)，progesterone (P)
and androgens (A) .
During the process of follicular maturation, binding of FSH
to receptors in the granulosa cells causes granulosa cell
proliferation and continuously increased production of
estradiol (E2). The follicle with the greatest number of
granulosa cells , FSH receptors and the highest E2 production
becomes the dominant follicle from which ovulation will
occur .The theca cells secrete A, which serve as the precursors
for E production by the granulosa cells.
The basic substance provides for sex hormone
synthesis is cholesterol from food intake. E is
secreted through a two-cell mechanism . Androgens
are first secreted by the theca cells, these A enter the
granulosa cells by diffusion , where they are
aromatized to E.
After ovulation, the mature follicle becomes to
corpus luteum .the luteal phase of the cycle is
characterized by a change in secretion of sex steroid
hormones from E predominance to P predominance.
As FSH rises early in the cycle and stimulates
mitosis of granulosa cells and production of E,
additional LH receptors are created in the
granulosa cells and theca cells .With the LH
surge at the time of ovulation ,these LH
receptors bind LH and convert the enzymatic
machinery of the granulosa and theca cells to
facilitate production of P.
Androgens are metabolic precursors of
E and are found in small amounts in the
blood and urine of normal women. They
are secreted by the suprarenal cortex and
stromal cells of ovary.
Physiological actions of E and P
1. Uterus
• E:
accelerates
uterine
development,
myometrial
thickness ， uterine blood supply, smooth muscle
contractility and sensitivity to oxytocin.
• P: uterine blood supply increase, reduces smooth
muscle contractility and sensitivity to oxytocin.
2. endometrium
• E: stimulates the endometrial stroma thickens
and the glands proliferate，this is a proliferative
endometrium.
• P: converts the proliferative endometrium into a
secretory endometrium. After ovulation the
corpus luteum secretes both oestrogen and
progesterone,
and
these
bring
progestational changes in the endometrium.
about
3. cervical mucosa
• E:
the
endocervical
glands
secrete
quantities of thin ， clear, watery mucus.
large
On
drying， shows fern-like crystals.
• P: cervical mucus become thick , clouding, and
tenacious。 On drying，ellipsoid appeared. see
4. fallopian tube
• E:
augment
contraction,
the
amplitude
accelerates
of
rhythmic
fallopian
tube
development.
• P: reduces the amplitude of rhythmic contraction.
5. Vagina epithelium
• E: Stimulates vaginal epithelium proliferates and
mature, glycogen increase，causes the vaginal
PH to be low (PH=4～5).
• P: accelerates vaginal epithelial cells shedding.
6. breasts
• E: mammary gland duct proliferates. high level
of E inhibits milk secretion.
• P: accelerates the growth of alveolus and lobular.
high level of P inhibits milk secretion.
7. Body temperature regulation
E: no action
• P: make basal body temperature (BBT)rises
0.3 ～ 0.5oC
by
affect
thermoregulating center.
Hypothalamic
8. H-P
E: there are both negative and positive feedback
to H-P.
P: there is negative feedback only.
10. bone:
E：promote calcium deposits in bone.
Summary of ovarian events
Follicular phase
• LH stimulates theca cells to produce androgens
• FSH stimulates granulosa cells to produce oestrogens
• the most advanced follicle at mid-follicular phase
becomes the dominant follicle
• rising oestrogen produced by the dominant follicle
inhibit pituitary FSH production
• declining FSH levels carse atresia of all but the
deminant follicle
Ovulation
• FSH induces LH receptors
• LH surge
• proteolytic enzymes within the follicle carse follicular
wall breakdown and release of the oocyte
The luteal phase
• the corpus luteum is formed from granulosa and theca
cells retained after ovulation
• progesterone produced by the corpus luteum is the
dominant hormone of the luteal phase
• A delicate balance of FSH and LH is required for early follicular
development. The ideal situation for the initial stages of follicular
development is low LH levels and high FSH levels, as seen in the
early menstrual cycle. If LH levels are too high, theca cells produce
large amounts of androgens carling follicular atresia.
• The interrelation of Hypothalamic-pituitary ovarian Axis (H-P-O Axis)