1.4 HUMAN FEMALE REPRODUCTIVE SYSTEM DEGREE CLASSES.pptx

Herbert lectures 2015
Female reproductive physiology
The normal female reproductive physiology is
characterized by the following events:
Menstrual cycle
mating
fertilization
Conception
Pregnancy
Parturition
Lactation
The above physiological events are adapted by
the structural and hormonal changes of the
females body .

Female reproductive functional
anatomy
The primary female sex organs (gonads)
are the ovaries.
The accessory ducts of the female system
include the uterine tubes, uterus, and
vagina.
The ovaries and the duct system are the
internal genitalia.
The external genitalia, also known as the
vulva, include the mons pubis, labia and
clitoris.

Functional anatomy cont…
 Ovaries: development of follicles/eggs, corpus luteum ( produce
hormones)
 Oviducts (Fallopian tubes)
 Deliver eggs to uterus and fertilization in the ampulla region
 Uterus (womb): implantation, nourishment of growing fertilized egg,
secretion of hormones, protection and child birth. Made up of:
 Perimetrium; outer most wall
 Endometrium: inner lining
 Myometrium: muscular wall
 Vagina
 Receives penis in intercourse
 Birth canal
 Vulva (lips of vagina):
 Labii major and minor
 Clitoris: homologous to penis (erectile tissue)
 Mammary glands
 Secrete milk
 Pelvis:
 Supports reproductive organs
 Wide and shallow: allows easier birth

Sexual life in females
 Life span of a female can be divided into three periods.
First period
 Extends from birth to puberty.
During this period primary and accessory sex organs do not
function, they remain quiescent.
Puberty occurs at the age of 12 years.
Second period
 Extends from onset of puberty to menopause.
The first menstrual period is known as menarche and the
permanent stoppage of the menstrual cycle is menopause, which
occurs at the age of 45 to 50 years.
During the period between menarche and menopause, women
menstruate and reproduction is possible.
Third period
This period extends from menopause to the rest of the life.
 Menstruation ceases at menopause.

Menstrual Cycle
These are cyclic events that take place in a
rhythmic fashion during the reproductive
period of the woman’s life.
 The menstrual cycle starts at the age of 13
to 15 years, which marks the onset of
puberty.
The duration of menstrual cycle is usually 28
days. But, under physiological conditions it
may vary between 20 and 40 days.

Release of germ cells
Release of germ cells is cyclical - this is reflected by
the corresponding cyclic structural and functional
changes throughout the female reproductive system
(ovary and accessory organs – uterus, vagina, and
cervix ).
These changes are dependent on two inter-related
cycles; the ovarian and the uterine (menstrual) cycle.
Both these cycles, although variable, last
approximately 28days.
The menstrual cycle is controlled by the ovarian
cycle via sex hormones.

Ovarian Cycle
 The ovarian cycle is made up of monthly series of events
associated with egg maturation.
 It consists of two phases.
Follicular phase
Luteal phase
 The follicular phase is a period of follicle growth usually
extending from day 5 till the time of ovulation, which takes
place at about the 14th day.
 The Luteal phase is the period of corpus luteum activity
usually from day 14 to day 28.
 Ovarian cycles may vary in length. The follicular phase may
range from seven to 26 days long. However, the Luteal
phase is constant 14 days.
 During the follicular phase, the primordial follicle of the ovary
develops into the Graafian follicle.

Oogenesis
Gamete production in females is known as
Oogenesis. Female gamete formation is initiated in
the Embryo.
The potential germ cells develop early in fetal life,
starting at about the 5th or 6th week.
In the fetal period, the Oogonia ( the diploid stem
cells of the ovaries) multiply rapidly by mitosis.
They start meiosis but are arrested at the first
prophase ( Prophase 1), the Oogonia will replicate
their DNA and become primary Oocytes.
At birth there are about 2 million potential egg
cells, primary Oocytes. At this point, follicle cells
surround the primary Oocytes and thus, the ovary
contains primordial follicles.

Oogenesis cont…
 By puberty there are only 400,000 primordial follicles left,
about 400-500 of these will be released and ovulated in all the
monthly reproductive cycles.
 At this time, a certain few (5-20) are activated each month.
However, only one is selected to continue meiosis 1.
It completes the first meiotic division to yield two haploid
cells of different sizes.
The smaller one is known as the first polar body. It will
play no role in fertilization or development.
The larger cell, which contains nearly all the cytoplasm and
the organelles, is the secondary oocyte.
 The first polar body may undergo meiosis II and produce two
smaller polar bodies or it may simply degenerate.
 The secondary oocyte, on the other hand is arrested at second
metaphase ( metaphase II), and will not complete meiosis II
unless fertilization by a sperm occurs.
 If a sperm does penetrate the secondary oocyte, it will quickly
complete meiosis II, Producing an ovum and a second polar
body.

Follicle
components are:oocyte, granulosa cells
and theca layers
ROLES:
contains oocytes
 provides nourishment for the oocyte
 produces steroid hormones

Follicular development
 The first step is the conversion of primordial follicles into primary follicles.
 Several primordial follicles will be activated and the squamous – like cells
surrounding the primary oocyte will grow and become cuboidal cells. These
follicles are now considered primary oocytes.
 In the next step, several but not all primary follicles will become secondary
follicles.
 First, the follicle cells will proliferate; forming multiple layers ( they’re now known
as granulose cells). After 7 days, one of the follicles outgrows the others. The
others start involuting and become atresic or undergo follicular death.
 The granulose cells in dominant follicle will multiply and the follicle will become
more stratified, acquire FSH receptors and theca cells.
 The granulose cells will also secrete a glycoprotein – rich thick transparent
membrane called the zona pellucida around the oocyte.
Clear serous fluid, liquor folliculi will begin to accumulate between the granulose cells,
Fluid- filled spaces will coalesce to form a cavity known as a antrum.
The next and final step is for one chosen follicle to become a vesicular or Graafian
follicle.
 The antrum will continue to expand until it isolates the oocyte along with its
surrounding capsule of granulosa cells called cumulus oophorus which
become columnar and form corona radiate, on a stalk on one side of
the follicle.
 As the follicles grow they shift towards the peripheral part of the ovary.

Follicular sheath or theca folliculi
Spindle shaped cells from the stroma of cortex
in the ovary form a follicular sheath.
It divides into two layers:
Theca externa (outer most)
Theca interna (innermost)
Highly vascularised
Close to the membrane granulosa
Contain lipid granule containing cells which are secretory
in nature

Follicular steroidogenesis
1. Theca
-makes androgen
-androgen production stimulated by LH
-androgen diffuses into granulosa cells
2. Granulosa cells
-contain aromatase
-convert androgen precursors to estradiol
(estrogen)
-FSH stimulates aromatase activity and thus
stimulates estrogen production.
There is therefore need for both theca and
granulosa cells in the 2-cell theory of estrogen
synthesis.

Hormonal control of ovarian changes
 The female reproduction cyclic activities in a 28-day cycle are
coupled to a hormonal control mechanism.
 On day 1, the release of Gonadotropin-releasing hormone (GnRH)
from the hypothalamus causes an increase in the production and
secretion of follicle-stimulating hormone and Luteinising hormone
from the anterior pituitary gland.

 The cycle is then controlled by the cyclic release of these two
anterior pituitary hormones, and the cyclic rhythm originates in the
hypothalamus as earlier mentioned.
 FSH increases early in the cycle, promotes development of egg and
follicle
 LH peaks in middle of cycle, triggers ovulation, completion of the 1st
meiotic division and formation of corpus luteum

 The follicle-stimulating hormone and Luteinising hormone, act
together to stimulate production of the female sex hormone,
estrogen from the follicular cells.
 Estrogen peaks just before ovulation, but is important in the 2nd
half of the cycle as well (some is produced by the corpus luteum)

Hormonal control of ovarian
changes cont…
 The rising estrogen levels in the plasma cause a decrease in pituitary
release of FSH and LH, while at the same time, stimulating the pituitary to
stockpile these two hormones.
 Eventually, as estrogens levels continue rising, they reach a threshold level
and exert a very different effect on the pituitary. This event is a sudden
large release of the accumulated LH and FSH.
 This LH surge is what stimulates the primary oocyte of the dominant follicle
to complete meiosis I.
 The LH surge is also what triggers ovulation at about day 14.
 The LH surge also transforms the ruptured follicle into the corpus luteum;
the corpus luteum will secrete progesterone and estrogen.
 Eventually, as plasma progesterone and estrogen levels rise, they'll
work together to inhibit any further LH and FSH release.
 This helps prevent any further follicle growth or ovulation in case
pregnancy occurs in the subsequent days.
 However, as LH levels decline, the corpus luteum will begin to degenerate.
 Once the corpus luteum degenerates, FSH and LH release will begin to
rise and the cycle will begin again.

Hormonal control of ovarian changes
cont…

Other functions of estrogen
1. Breast development
 Stromal tissues
 Ductule system
 Deposition of fat in the ductile system
2. other secondary sex characteristics
 Hair distribution
 Skin
 Body shape
 voice
3. skeletal effects
 increased osteoblstic activity but with early fusion of the epiphyseal plates
 Reduced or complete stoppage of estrogen secretion leads to osteoporosis in old age and bones
are prone to fracture.
4. Improved learning learning and memory
5. cardiovascular benefits
6. growth and other changes of reproductive tract (uterus, fallopian tubes, ovary,vagina )
 Vaginal changes
 From cuboidal to stratification, more resistant to trauma and infection.
 Reduces vaginal pH, more acidic (certain common vaginal infections e.g. gonorrheal vaginitis are cured by
administration of estrogen)
7. metabolism
 fat deposition (in subcutaneous tissues, breasts, hips & thighs)
8. Electrolyte balance
 Sodium and mineral retention

Indicators of ovulation
Some women feel a light tension in the breasts.
Sometimes a little pain can be felt at the left or
right ovary. This is caused by an increased blood
flow to the ovaries and an involuntary
contraction of the ligaments that pulls the ovary
closer to the fallopian tube (which allows easier
passage for the released egg into the tube).
The cervical mucus becomes much more
abundant (usually 10 to 14 days into a normal 28
day cycle). This creates an ideal medium for the
spermatozoa to swim in.

Determination of the ovulation time
By determining
Basal body temperature
Hormonal secretion in urine
Hormonal level in plasma
Using ultrasound scanning
Family planning by rhythm method can be
adopted, if the woman knows the day of
ovulation

The temperature method:
 At the day of ovulation, there is a
slight increase of about temperature
0.3° above the normal body
temperature.
 The only problem with this method is
that the temperature needs to be taken
very regularly under similar conditions
to be sure of the slight change

The testing method:
This test measures the level of the LH
hormone (Luteinising Hormone) in the
urine.
 It is normally advised that this test be
taken each day from the 11th day of the
cycle until a milky-blue appears in the
test (the colour may change depending
on the manufacturer).
 This is a very reliable test and gives
about 98% accuracy for the date of
ovulation.

Special features of Oogenesis
Although Oogenesis produces 4 haploid cells,
only one of them, the ovum, is a functional
gamete and the other 3 become polar bodies
and regress.
The unequal division of cytoplasm is essential to
ensure that the fertilized ovum has enough
nutrients to survive the journey to the uterus.
The small number of cells that even complete
the first meiotic division of the 400,000 primary
oocytes present at puberty, only about 400-500
secondary oocytes will be ovulated and only
those fertilized will undergo meiosis II.
Meiosis is arrested twice during Oogenesis.

Ovulation
Occurs when the ovary wall ruptures and expels the
secondary oocyte, still enveloped by its corona
radiate and zona pellucida, into the peritoneal cavity.
Ovulation occurs usually on 14th ( 12th -14th ) day of
the menstrual cycle.
The pituitary produces a surge of LH secretion, and
associated with the LH surge is the beginning of
secretion of the progesterone hormone by the theca
cells.
Luteinising hormone together with the progesterone
stimulate the formation of blood vessels in the ovary.
The blood flow in the thecal layers increases with
subsequent increase in the rate of transudation of
fluid into the Graafian follicle; this is assisted by
prostaglandins secreted by the granulose cells.

Ovulation cont…
The follicle swells up and protrudes against the wall
of the ovary forming a stigma, the thecal cells
secrete a proteolytic enzyme into the follicular fluid,
this weakens the follicular capsule and
degeneration of the stigma within 30 minutes of its
formation.
Within minutes of the rapture, the follicle
invaginates, the Oocyte and surrounding layers of
granulose cells, the corona radiate leave their
vesicle and enter the abdominal cavity.
The ovum must be fertilized soon i.e., with in 24 to
48 hours after ovulation because only during this
time, it is viable for fertilization. This is the fertilizing
capacity of the ovum. If fertilization does not occur,
the ovum degenerates

Luteal phase
The phase encompasses al the sequence of
events that transform the granulose cells that
remain in the ovary after ovulation into a
hormone secreting gland, corpus luteum
This phase extends between 15th to 28th day of
the menstrual cycle. Following ovulation, the
ruptured follicle collapses and the antrum fills
with clotted blood, corpus hemorrhagicum.
This hemorrhage will eventually be absorbed.
The remaining granulose cells will enlarge,
transform into lutein cells that form a yellow
body; the corpus luteum and the Luteal phase
will begin.

Luteal phase cont…
 The corpus luteum acts as a temporally endocrine gland and secretes
large quantities of progesterone and small amount of estrogen.
 The Luteinising hormone from anterior pituitary gland influences
development of the corpus luteum and the secretion of these hormones.
 The hormones secreted are essential for maintenance of pregnancy.
 If fertilization occurs corpus luteum increases in size, now transformed into
corpus luteum graviditatis ( verum) or corpus luteum of pregnancy. It is
active secreting estrogen and progesterone until the placenta is formed
and ready to take over its function, which occurs at about the third month
of pregnancy.
 Progesterone remains high in pregnancy, preventing further ovulation
during embryonic development.
 Abortion occurs if the corpus luteum becomes inactive or removed before the
onset of hormonal secretion from the placenta.
 If the ovum is not fertilized, the corpus luteum reaches maximum
development about one week after ovulation, and then it degenerates
into the corpus luteum menstrualis or spurium
 All that will remain following degeneration is a whitish scar known as the
corpus albicans

Ovarian Cycle -summary
The hypothalamus releases GONADOTROPHIN RELEASING
HORMONE (GnRH) which stimulates the Ant. Pituitary to
secrete FSH. This acts on the ovarian follicle, to initiate
maturation and become the Graafian follicle which will release
the ovum into the fallopian tubes (ovulation).
 The developing follicle synthesizes oestrogens which act to
inhibit production of GnRH and FSH by the hypothalamus and
pituitary respectively.
The fall in FSH levels and the increase in oestrogens cause
the Ant. Pit. to release LH. LH triggers ovulation 12 hrs later by
a multicomponent mechanism.
The ruptured follicle becomes the CORPUS LUTEUM, which
in turn starts to produce both oestrogens and
PROGESTERONE.
 In an infertile cycle, the corpus luteum only lasts for 10 days
after which it regresses. If pregnancy does occur the corpus
luteum is maintained for at least 3 months.

Uterine changes
 The uterine events also take a 28 day
cycle of the menstrual cycle.
 The uterine cycle is a series of changes
that the uterine endometrium goes
through every month in response to the
fluctuating levels of ovarian hormones.
 During each menstrual cycle, the
changes in uterus take place in three
phases namely:
 Menstrual phase
 Proliferative phase
 Secretory phase

Menstrual phase
 Days 1-5 of the cycle are known as the menstrual phase.
This is the phase during which bleeding occurs.
 The day when bleeding starts is considered as the first day of
the menstrual cycle.
 Two days before the onset of bleeding, that’s the 26th or 27th
day of the previous cycle, there is sudden reduction in the
release of progesterone and estrogen from the ovary
because of the degeneration of the last cycle’s corpus
luteum.
 The reduced level of these hormones is responsible for
menstruation.
This triggers the shedding of all but only the deepest layer
( the stratum functionalis) of the endometrium.
 The detached portion of the endometrium as well as blood
will pass through the vagina as the menstrual flow ( menses),
causing menstrual blood flow ( average blood loss about 40
mL; another 40 mL of extracellular fluid & cells are also lost).
 During this phase, FSH levels are rising and as a result,
follicular development has begun to proceed and follicle
secretion of estrogen has begun.

Proliferative phase
 Day 6-14 are known as the Proliferative phase.
As follicular development proceeds, blood
estrogen levels rise.
This estrogen causes the regeneration of the
stratum functionalis.
The endometrium grows thicker and becomes
more vascularised and glandular. At this time,
cervical mucus begins to get less viscous.
Ovulation occurs at the end of the Proliferative
phase and coincides with the beginning of the
next phase.

Secretory phase
This is the final phase, days 15-28, during this
phase, the endometrium prepares for the
implantation of an embryo.
During this phase, the corpus luteum is active and
secreting progesterone and estrogen.
The progesterone acts to thicken the uterus even
more and become even more vascular and
glandular.
The endometrium also begins to secrete nutrients
into the uterine cavity, so as to support an embryo
prior to implantation.
The rising progesterone also causes cervical
mucus to become viscous again ( forming the
cervical plug), which helps prevent bacteria or any
more sperm from entering the uterus.

Progesterone role in ending the
menstrual cycle
As progesterone levels rise, they inhibit the release
of LH.
Without LH, the corpus luteum begins a steady
decline.
As the progesterone declines, the endometrium
begins to synthesize vasoconstrictive chemicals.
The spiral arteries become constricted and the outer
endometrial cells are denied oxygen.
More and more endometrial cells begin to die and eventually
the endometrial capillaries will rupture and blood and dead
cells will begin to slough off through the vagina. And now
we’re back to day 1 of a new cycle.

The uterine cycle- summary
The uterine cycle follows the ovarian cycle, which makes
sense since it is dependent on the different steroids
produced during different phases of the follicular cycle.
1. Proliferation phase
 the endometrium proliferates, becoming thicker
 follicular estradiol stimulates proliferation
 It coincides with the follicular phase
2. Secretory phase
 development of secretory glands
 development of spiral arteries
 lots of secretions
 dependent on progesterone (from CL)
 It coincides with the luteal phase
3. Menstruation
 loss of Luteal progesterone following luteal regression leads to
sloughing of tissue & loss of blood from spiral arteries

Ovarian and Uterine cycle
Ovarian and uterine cycle superimpose to
each other.

Other roles of progesterone
Breast development
Lobule and alveoli formation
Enlargement of breasts and increases fluid
secretion in the subcutaneous tissue.
Electrolyte balance
In small doses sodium and water retention
In large doses excretion of sodium and water.
Vaginal changes

Female Sexual Response
The female sexual response is similar to the male's in
many ways. The clitoris, vaginal mucosa, and breasts
can engorge with blood, analogous to erection in
males. The clitoris is analogous to corpus carvenosa
and glans penis, the labia minus is analogous to
corpus spongiosum.
The main difference is the fact that female orgasm is
unaccompanied by ejaculation.
There are two major kinds of vestibular glands,
greater vestibular glands that open through a pair of
large ducts at the urethral orifice and lesser vestibular
glands that open at the entry into vaginal orifice.
These glands secrete a mucus secretion which
lubricate the vagina and so provide for smooth
intercourse

Female Sexual Response cont…
The excitement phase prepares the vagina for coitus or
sexual intercourse.
Vasoconstriction, filling of the erectile tissue with blood
occurs because of increased flow in the arteries and
constriction of the veins, especially in the clitoris, but also in
the ovaries, labia minora, and breasts.
 Myotonia, increased muscle tension, causes erection of the
nipples; tension in the arms, legs, and other skeletal
muscles; and sustained or rhythmic contractions of the
smooth (and skeletal) muscles.
Many of these characteristics continue into the plateau
phase.
The outer third of the vagina becomes vasoconstricted, while
the inner two thirds becomes slightly expanded, and the
uterus becomes elevated, all in preparation for receiving
sperm.
Breathing and heart rates increase, not because of physical
activity, but because of stimulation from the autonomic
(sympathetic) nervous system.

Female orgasm
Typically it is harder to stimulate a woman to reach
orgasm, and the man needs to take care to make
sure the woman is ready when he is.
 Women, however, can have multiple orgasms, and
once aroused, are often not ready to “quit” when,
physiologically, the man’s body is progressing to the
resolution phase.
 Many women appreciate continued, gentle
stimulation after coitus.
 A male normally has only one orgasm (and some
men may fall asleep during/after the resolution phase
which follows).
In the female, orgasm involves the uterus and outer
vagina but not the upper two thirds of the vagina.

Definitions of menstrual cycle
abnormalities
A cessation of menses is known as
amenorrhea.
As one's age increases, menstrual periods
become erratic and increasingly irregular.
Eventually, ovulation and menses cease
entirely. This is known as menopause.
Dysmenorrhea- Irregular menstruation with
pain occurs

Fertilization
 Ovum is released from the Graafian follicle into the abdominal
cavity at the time of ovulation.
 The ovum enters into the fallopian tubes; the fimbriated end of
the fallopian tube is placed near and around the ovary. The cilia
of the fallopian tube beat continuously and facilitate entry of
ovum into the fallopian tube.
 After sexual intercourse and ejaculation, some sperms are
transported through the uterus to the fallopian tube (ampulla)
where fertilization takes place. The rate of motility of sperms in
female genital tract is about 3mm/minute. The sperms reach in
fallopian tube in about 30-60 minutes after sexual intercourse.
The uterine contractions during sexual intercourse act to facilitate
the movement of sperms.
 An average ejaculate contains about 300,000,000 sperm or so.
 About 20% of them are non-functional
 At the entrance to the Fallopian tube only 300,000 sperm are left
and only 100 or so make it to the upper end of this tube

Fertilization
Sperm modification
The spermatozoa undergo certain modifications
including 3 major steps: capacitation,
hyperactivation and acrosome reaction.
 Capacitation takes about 5-6 hours. It is a calcium
dependent process involving activation of ATPase,
redistribution of mannose receptors, glycoproteins and
glycolipids on the sperm surface. Angiotensin converting
enzyme (ACE) is released during capacitation and
assumed to participate in the acrosome reaction.
 Hyperactivation. Hyperactivated motility results in
enhanced lateral head displacement, reduced linearity,
beat frequency and flagellar curvature.

Fertilization
Sperm modification cont…
Acrosome reaction. The spermatozoon initially
binds to zona pellucida, a semipermeable
membrane.
The acrosome reaction involves fusion of outer and inner
acrosomal membranes.
It involves changes in membrane potentials, modification
of pH, swelling and release of acrosomal enzymes.
This reaction is accompanied by modifications in the
sperm plasma membrane.
Acrosome reacted spermatozoon may pass through
zona pellucida into the perivitelline space (this
process may take about 1 hour).
The fusion occurs between sperm plasma membrane
and oolemma.

Fertilization
The sperm enters the ovum, by penetrating the
multiple layers of granulose cells, the corona
radiata. Hyaluronidase and proteolytic enzymes
present in the acrosome of the sperm facilitate
this.
Though many sperms reach the ovum, only one
enters it.
Fertilization causes rapid changes leading to
zygote formation, When 1 sperm penetrates an
egg reaction take place on the surface of the egg
that block penetration by other sperm.
Proteolytic enzymes from acrosome of the first
entered sperm diffuse through the structures of
zona pellucida. This is necessary because
polyspermy is lethal

Fertilization
The egg cell nucleus is triggered into
finishing meiotic division, in the next 11
hrs following fertilization finally producing
a haploid nucleus
The sperm loses its tail and its nucleus
swells
The 2 haploid nuclei, from the sperm and
egg, fuse to form a single nucleus, the
joining of the genetic information occurs.
This results into a single cell called a
zygote and end of fertilization.

Mr.SPERM + Mrs. EGG

Guide line to a Boy or Girl!!
 Interestingly, there are some things a couple can do to
increase their chances of having a baby of a given sex.
 It has been found that sperm which contain an X
chromosome tend to live longer than Y sperm, so having
intercourse a couple days prior to ovulation increases the
chances of a girl baby.
 On the other hand, Y sperm swim faster than X sperm, so
having intercourse right at ovulation can increase the
chances of a boy baby.
 As previously mentioned, at the time of ovulation, a woman’s
body temperature and cervical mucus are “right” to help
sperm survive.
 The contractions caused by orgasm and the prostaglandins
in semen help propel sperm up into the uterus, and from
there, up the Fallopian tubes.
 An egg is fertilized near the end of the Fallopian tube, then
finishes meiosis, the nuclei unite, and the embryo starts
dividing as it begins to travel to the uterus.

Cleavage
 The zygote undergoes mitotic cell divisions (without cell
growth) called cleavage. Cleavage gives rise to a
blastocyst.
 Initially the cell (zygote) divides mitotically, giving rise to a
mulberry- like mass, called morula with in the first three
days after fertilization.
 The morula moves down fallopian tube to uterus. The zygote
spends the next few days (3-5 days after fertilization)
traveling down the Fallopian tube and rapidly multiplying the
number of cells by mitosis (about once every 20 hours).
 Movement along tube is caused by cilia, which sweep the
zygote along, as the zygote moves down the fallopian tube,
its cells divide further to form a blastocyst (hollow sphere)
and the rapid cell division taking place up to the blastocyst
stage occurs without significant increase in total mass
compared to the zygote.

Cleavage
Along the wall of the cavity, a structure called a
“blastocyst” (about 100 cells) develops with an inner
core and an outer shell of cells.
The outer layer of the blastocyst, the trophoblast gives
rise to the fetal part of the placenta and fetal
membranes (yolk sac, amniotic sac,allantois and the
chorion) that nourish and protect the inner cell mass
which develops into the embryo proper.
Summary: i.e. Single Cell -> Morula (berry-shaped) ->
Blastocyst.
 After reaching the uterus the developing zygote
remains freely in the uterine cavity for 2-4 days before
implantation.
Thus it takes about a week for implantation after the
day of fertilization

Nutrition of the developing zygote
For the first 7 days the embryo has been
using food materials originally stored in the
egg cell and secretions from the
endometrium, called the uterine milk.
Now it imbeds itself into the uterine lining so
that it can be nourished by the mother.
Elaborate connections are made between
embryonic and maternal tissue, forming the
placenta

Implantation
A layer of spherical cells called the trophoblast cells is
formed around the blastocyst; these cells release
proteolytic enzymes over the surface of the endometrium
on the dorsal wall.
The proteolytic enzymes digest cells of endometrium; the
blastocyst burrows inside the endometrium and implants
itself.
The implantation process is completed in the in the 2nd
week after fertilization (by the 10th day after fertilization),
the implanted blastocyst is now an embryo.
The fully implanted blastocyst is now an embryo.
 7 - 12 days post-ovulation, trophoblast cells engulf and
destroy cells of the uterine lining creating blood pools, both
stimulating new capillaries to grow and foretelling the
growth of the placenta.

Placentation
 This is the formation of the placenta.
 The placenta is a combination of fetal and maternal tissues.
 The trophoblast cells form cords that grow into the
endometrium
Blood capillaries grow into the cords from the embryo; by
day 16 after fertilization blood flow begins into capillaries.
 At the same time, on the maternal side, sinuses develop that
are perfused with blood from the uterine vessels surrounding
the trophoblast cords.
 The cords branch extensively as they continue to grow, forming
the placental villi on the chorionic membrane into which
embryonic capillaries grow, these carry fetal blood and they are
surrounded by sinuses filled with maternal blood.
 The two blood supplies remain separated by several layers and
no mixing occurs of the blood from the mother and fetus
 Blood vessels enter and leave the placenta through the
umbilical cord, which is connected, to the baby at the site of the
belly button (navel).

The Placenta and its roles
 The placenta is a link between the fetus and the mother and
provides both a physical attachment and physiological
connection between the mother and the fetus.
Functions of the placenta
 Nutrients compounds necessary for the development of the
fetus diffuse through the mother’s blood into the fetal blood
through the placenta.
 Metabolic end products and other waste products from the
fetal body are excreted in the mother’s blood through the
placenta.
 Oxygen necessary for fetus is received from maternal blood
and carbondioxide from the fetal blood diffuses into the
mother’s blood through the placenta
 The placenta acts as an endocrine gland and secretes
hormones:

Placental transfer
Pressure gradient between the fetus and maternal
blood favors exchange of O2, 50 mmHg and 30
mmHg maternal and fetal blood respectively.
Factors that favor diffusion of O2 from mother to
fetus include:
Fetal Hb (carry 20-50% of O2 more than adult Hb)
Hb concentration is 50% in fetal blood than maternal blood.
Bohr effect – as CO2 (and acid) is transferred to mother, HbF
binds more oxygen, and HbA (mother) binds less O2.
CO2 – simple diffusion (even at 2-3 mmHg, diffusion
occurs).

Placental Transfer cont…
Nutrients
Facilitated diffusion (especially glucose)
Simple diffusion (most nutrients, electrolytes)
Waste
Simple diffusion of urea, uric acid, creatinine
etc.

Human Chorionic Gonadotropin
The secretion of hCG begins 8-9 days after
fertilization and peaks at 8-9th week and
declines to low levels by the 16th week when
the placenta is capable of taking up the role of
the corpus luteum.
Functions
Prevents involution of corpus luteum
Corpus secretes more progesterone and estrogen
Prevents menstruation
Decidua cells swell
Stimulates interstitial cell development in male fetuses
Secretes more testosterone
Male develops male sex organs

Placental Estrogens
Secreted by syncytiotrophoblast
Toward end of pregnancy, estrogen is 30X
normal
Function
Enlargement of mother’s uterus
Enlargement of mother’s breasts and growth of breast
ducts
Enlargement of external genitalia
Relaxation of SI and pubic joint ligaments
Mitogenic effect on fetus

Placental Progesterones
Secreted by syncytiotrophoblast
Secretory rate 10X normal
Replaces corpus luteum as primary
source of estrogens
Functions
Decidual cell development in endometrium
Decreases contractility of pregnant uterus
Promotes breast development

Human Chorionic
Somatomammotropin (hCS)
a.k.a. human placental lactogen
Secreted by placenta starting at 5th
week
Functions (not well known)
May aid breast development
May have similar effects to growth hormone
Decreases insulin sensitivity in mother

Relaxin
Secreted by ovaries and placenta in
response to hCG
Relaxes ligaments of symphysis pubis,
may cause cervix effacement.

Endocrine Alterations in Pregnancy
Pituitary – enlarges, increases
corticotropin, thyrotropin, and prolactin
production
Adrenal cortex – increased
glucocorticoids, aldosterone
Thyroid – increased thyroxine
Parathyroid – increased parathormone

Pregnancy
Weight gain
Average 24 lbs
7 lbs fetus
4 lbs amniotic fluid, placenta, fetal membranes
2 lbs uterus
6 lbs blood, extracellular fluid
3 lbs fat
Increase in appetite – can increase weight gain
even more if mother isn’t careful.

Pregnancy
Increased metabolic rate
Nutrition
Iron –for baby and mother’s extra blood
Vitamin D – for calcium
Vitamin K – for clotting factors
Increased blood volume (1-2 liters)
Increased CO

Pregnancy
Increased respiratory rate (due to increased
metabolism as well as effects of uterus against
diaphragm)
Amniotic fluid
From fetal renal excretion
Amniotic membrane
Turnover every 3 hours

Preeclampsia, Eclampsia
Hypertension, proteinurea
Excess salt and water retention
Arterial spasm in kidneys, brain, and liver
Due to hormones?, autoimmunity?,
allergy?
Eclampsia (coma, death) is severe form of
preeclampsia that occurs shortly before
birth

Parturition
Increase in uterine activity
Estrogen/progesterone ratio
Oxytocin
Stretch of uterine smooth muscle
Cervical stretch/irritation
Braxton Hicks contractions – weak periodic
contractions before true labor begins
Labor
Positive feedback???
Cervix pressure = reflex uterine contractions ,
pituitary secretion of oxytocin 

Parturition
Abdominal muscle – reflexively contract due to
painful stimuli from uterus and birth canal.
Stages of labor
First – cervical dilation and effacement – (8-24 hours w/
first pregnancy), amnion rupture
Second – movement of fetus through cervix and vagina
(30 min – 2 hrs w/ first pregnancy)
Uterine involution
Lasts 4-5 weeks, facilitated by lactation

Summary of the role of hormones in parturition
 Oxytocin – causes contraction of smooth muscles
 The number of receptor for oxytocin increase in the wall of the
uterus in the later stages of pregnancy under the influence of
estrogen, thus the uterus becomes more sensitive to oxytocin.
 Estrogen – increases the force of contraction by:
 Increasing the number of oxytocin receptors in the uterine wall.
 Accelerating the synthesis of prostaglandins
 In the later stages of pregnancy, the quantity of estrogen
released is much greater than that of progesterone from the
uterus.
 Prostaglandins – increases the force of contraction by increasing the
concentration of intracellular calcium ions in the smooth muscles of the
uterus.
 Secreted from uterine tissues, fetal membranes, and placenta
 Cortisol – enhances uterine contraction and plays an important role in
helping the mother to withstand the stress during labor.
 Relaxin
 Softens the cervix and loosens ligaments of the pubic symphsis
 Suppresses the inhibitory action of progesterone
 Also increases the number of oxytocin receptors in the
myometrium

After Parturition
After birth, decreasing progesterone and
estrogen and increasing oxytocin help reduce
the uterus to its normal size (involution).
It has been found that laying the baby on the
mother’s abdomen immediately after birth will
stimulate the production of oxytocin, helping
shrink the uterus faster.
The baby’s sucking on the mother’s nipples
stimulates nerve endings that also stimulate
the production of oxytocin, so immediate
postpartum nursing can also help return
uterus to proper size.

Lactation
Lactation describes the secretion of milk
from the mammary glands, the process of
providing that milk to the young, and the
period of time that a mother lactates to
feed her young.
The process occurs in all female
mammals, humans inclusive and it is
commonly referred to as breastfeeding or
nursing.

Lactation
Growth of ductal system – estrogen (and
other hormones GH, prolactin,
glucocorticoids, insulin)
Lobule-Alveolar system – progesterone
Initiation of lactation – prolactin, human
chorionic somatomammotropin
Colostrum (proteins, lactose, little fat) – secreted
immediately before and after parturition
Milk – after estrogens and progesterones decrease
post partum.
Nursing – stimulates prolactin secretion,
maintains milk production

Lactation.
The milk synthesizing units

Lactation
The hormone prolactin must be present for
milk synthesis to occur.
On the walls of the lactocytes (milk-producing
cells of the alveoli) are prolactin receptor sites that
allow the prolactin in the blood stream to move
into the lactocytes and stimulate the synthesis of
breast milk components.
Lactogenesis takes a course of three stages
namely:
Lactogenesis I
Lactogenesis II
Lactogenesis III

Lactation
Lactogenesis I & II
During pregnancy and the first few days
postpartum, milk supply is hormonally driven –
this is called the endocrine control system.
Essentially, as long as the proper hormones are
in place, mom will start making colostrum about
halfway through pregnancy but high levels of
progesterone inhibit milk secretion and keep the
volume "turned down." (Lactogenesis I)
At birth, the delivery of the placenta results in a
sudden drop in progesterone/estrogen levels.
This abrupt withdrawal of progesterone in the
presence of high prolactin levels cues
Lactogenesis II (copious milk production) around
30-40 hours after birth.

Lactation
Lactogenesis III
After Lactogenesis II, there is a switch to the autocrine (or
local) control system.
This maintenance stage of milk production is also called
Lactogenesis III.
In the maintenance stage, milk synthesis is controlled at the
breast -- milk removal is the primary control mechanism for
supply.
Milk removal is driven by baby's appetite. Although hormonal
problems can still interfere with milk supply, hormonal levels
play a much lesser role in established lactation.
Under normal circumstances, the breasts will continue to
make milk indefinitely as long as milk removal continues.
By understanding how local/autocrine control of milk
synthesis works, we can gain an understanding of how to
effectively increase (or decrease) milk supply.

Lactation
Regulation of lactation
Milk contains a small whey protein called Feedback
Inhibitor of Lactation (FIL) – the role of FIL appears
to be to slow milk synthesis when the breast is full.
Thus milk production slows when milk accumulates
in the breast (and more FIL is present), and speeds
up when the breast is emptier (and less FIL is
present). When the alveolus is full of milk, the walls
expand/stretch and alter the shape of prolactin
receptors so that prolactin cannot enter via those
receptor sites – thus rate of milk synthesis
decreases.


Lactation
The prolactin receptor theory suggests that
frequent milk removal in the early weeks will
increase the number of receptor sites.
 More receptor sites means that more
prolactin can pass into the lactocytes and
thus milk production capability would be
increased.
 As milk empties from the alveolus,
increasing numbers of prolactin receptors
return to their normal shape and allow
prolactin to pass through - thus rate of milk
synthesis increases.

Lactation
Milk ejection (let down) reflex
 Baby's sucking stimulates nerves in the nipple and
the nerves carry a message to the brain, and a
hormone, called oxytocin, is released from the
posterior pituitary gland.
 Oxytocin flows through the bloodstream to the
breasts, where it causes tiny muscle cells
(myoepithelial) around the milk glands to squeeze
milk out of the glands and into the milk ducts.
This is known as the let-down reflex or the milk
ejection reflex. The release of the hormone oxytocin
leads to the milk ejection or let-down reflex.

Lactation
Milk Let down cont…
Once your let-down is working well (usually by 2
weeks after delivery)
you may feel a pins-and-needles or tingling sensation
in your breasts when you nurse or pump.
Milk will usually drip from one breast while you are
feeding on the other side.
Sometimes your let-down will occur when you hear
your baby cry or think about nursing your baby.
 A well-functioning let-down reflex helps
ensure your breasts get emptied and your
baby is easily getting milk.

Lactation
Afterpains
The surge of oxytocin that triggers the milk
ejection reflex also causes the uterus to
contract.
During breastfeeding, mothers may feel
these contractions as Afterpains.
These may range from period-like cramps
to strong labour-like contractions and can
be more severe with second and
subsequent babies.

Lactation
Suppresses female ovarian cycles
Inhibits GnRH secretion from hypothalamus
Milk composition – water, fat, lactose, casein,
lactalbumin, ash (minerals), antibodies,
neutrophils, macrophages

Lactation
Physiological facts on breast feeding cont…
fat content of the milk is also determined by how empty the
breast is (emptier breast = higher fat milk), rather than by
the time of day or stage of the feed.
The more milk in the breast, the slower the speed of milk
production.
Storage capacity is the amount of milk that the breast can
store between feedings. This can vary widely from mom to
mom and also between breasts for the same mom
To speed milk synthesis and increase daily milk production,
the key is to remove more milk from the breast and to do
this quickly and frequently, so that less milk accumulates in
the breast between feedings:

Lactation
Physiological facts on breast feeding
Nursing is important in the bonding process, and for
that reason, too, it’s very important to let a baby
nurse immediately after birth.
There is evidence that human babies imprint on the
smell of their mothers’ nipples. Instinctively, when a
newborn is first trying to nurse, (s)he will turn his/her
mouth toward anything that brushes his/her cheek.
 Milk is a specially-designed food source that
exactly matches the nutritional needs of a baby, thus
every effort should be made to make use of
mother’s milk rather than artificial substitutes which
often are nutritionally lacking.

Fetal Physiology
Growth
1st
two weeks – placental , membrane development
>>>> embryo development
Thereafter, length is roughly proportionate to age
The rate of weight gain increases with age of fetus
Circulatory system
Heart begins beating at about 21 days
Red cells – yolk sac and placenta  liver  spleen
bone marrow

Fetal Physiology
Fetal Circulation
Fetal blood secures oxygen and food from
maternal blood instead of from fetal lungs and
digestive organs.
Deposits wastes into maternal blood
Substances diffuse between the maternal and
fetal blood through the placental membrane.
The exchange of substances takes place
without any actual mixing of maternal and fetal
blood.

Fetal Physiology
 Structures located in the fetal body important in fetal circulation include:
Two umbilical arteries
 Extension of internal iliac (hypogastric) arteries and carry fetal blood
to the placenta
 The umbilical vein
 Returns oxygenated blood from the placenta, enters the fetal body
through the umbilicus, extends up to the undersurface of the liver
and continues on as the ductus venosus
 The two umbilical arteries and the umbilical vein constitute the
umbilical cord and are shed at birth together with the placenta.
Ductus venosus
 Continuation of the umbilical cord along the surface of the liver,
drains into the inferior venacava
 most of the blood returning from the placenta by – passes the liver,
only a small amount of blood enters the liver by way of branches
from the umbilical vein and the liver.

Fetal Physiology
Foramen ovale
Opening in the septum between right and left atria, a
valve at the opening of the inferior venacava into the
right atrium directs most of the blood through foramen
ovale into the left atrium so that it by – passes the fetal
lungs.
A small amount of blood leaves the right atrium for the
right ventricle and pulmonary artery.
Ductus arteriosus
A small vessel connecting pulmonary artery to a
descending thoracic aorta.
It enables another portion of the blood to join the
systemic circulation without going through the lungs.
The placenta

Fetal circulation

Fetal Physiology
Respiratory System
Lungs are collapsed
Some respiratory movements, mostly inhibited
Nervous system
3-4 month – reflexes
Myelinization – complete after 1st
year of life

Fetal Physiology
GI tract
Ingest and absorb amniotic fluid
Meconium – mucus, bile, amniotic residue
Kidneys
Excretes urine during last half of pregnancy
Control of electrolyte and acid/base balance is
poor

Fetal Physiology
Metabolism
Mainly utilize glucose for energy
Storage of fat and protein (from glucose sources)
Calcium and Phosphate - most is accumulated
during ossification (last 4 weeks of gestation)
Iron – accumulates rapidly for hemoglobin synthesis
Vitamins
B12 and folate – for RBC, nervous system, growth
Vitamin C – for bone matrix and connective tissue
Vitamin D – bone growth (calcium absorption by
mother)
Vitamin E – function unclear, deficiency leads to
spontaneous abortion
Vitamin K – blood clotting

Time of Birth
Onset of breathing
Slightly asphyxiated state during birth
Sensory stimuli from cooled skin at birth
Hypoxia can occur due to compression of umbilical
cord, placental separation, anesthesia, excessive
uterine contractions
Infant can tolerate up to 10 minutes without O2
Lung Expansion – requires 60 mm Hg negative
pressure to inflate lungs the first time, by 40
minutes, respiration is near normal
Respiratory distress syndrome – prematurity and
lack of surfactant

Time of Birth
Changes in circulation
Systemic circulation – increased vascular resistance
due to loss of circulation through placenta
Pulmonary circulation – decreased vascular
resistance due to lung expansion, increased O2 also
causes vasodilation of pulmonary vessels
Closure of foramen ovale – due to above pressure
changes
Closure of ductus arteriosus – pressure changes
reverse blood flow through ductus, and increases
oxygen and prostaglandins cause constriction
Closure of ductus venosus – forces more blood
through liver sinusoids (prepares liver for functional
activity)

Nutrition of Neonate
Glucose stores are low
Liver function low (little gluconeogenesis)
Infants use stored fat and protein for
energy until mothers milk “comes in”
Neonates typically lose 20% of their
weight the first 2-3 days of life (mostly
fluid).

Miscellaneous Problems
Neonatal jaundice
Bilirubin is not efficiently removed from the
blood by the liver (mild jaundice)
Erythroblastosis fetalis – hemolytic anemia
increases bilirubin load (severe jaundice)
Renal function – immaturity of kidneys,
rapid fluid turnover, high metabolic rate
may lead to acidosis and dehydration

Miscellaneous Problems
Liver immaturity
Little bilirubin conjugation (see above)
Little plasma protein production  edema
Deficient gluconeogenesis  low blood glucose
Little blood clotting factors  abnormal coagulation
Body temperature
Surface area/ volume ratio  loss of body heat
Immunity
Passive immunity from mother (lasts 6 months)

Growth and Development
Birth – suckling
1 month – smiles
2 months – vocalization (other than crying)
3 months – head control
3 ½ months – hand control
5 months – roll over
6 months – sitting
7 ½ month – crawling
8 months – well developed grasp
9 months – pulls up
10 months – walks with support
11 months – stands alone
11 ½ - 12 months - walks alone

Birth control methods
 Are methods used by couples to avoid creating a baby.
 A number of birth control methods that prevent fertilization
(contraceptives) are available, but not all methods of birth
control fit into that category.
 In one method of “natural” birth control, the woman must have
very regular, predictable cycles and must keep a very accurate,
daily record of her body temperature (first thing in the morning
before getting out of bed) and condition of her cervical mucus in
order to determine when ovulation is occurring.
 The couple must, then, cooperate in being willing to forego a few
minutes of pleasure within several days of ovulation, in the
interest of building a strong, long-term, loving relationship.
 Since many women’s cycles are not that predictable and/or many
women do not wish to keep such detailed records and/or many
couples would rather not have to consult a calendar, a variety of
other methods of preventing ovulation or preventing sperm from
reaching the egg are available.

Birth control methods cont…
 Some of the hormone contraceptive pills prevent follicle
development and subsequent ovulation.
 Many of the barrier methods attempt to prevent sperm from
getting up into the uterus, either by introducing a physical
barrier between the penis and the uterus (cervical cap,
diaphragm, condom) or by killing the sperm (spermicidal
chemicals inserted into the vagina).
 However, none of these methods is a substitute for will power
and personal responsibility, and will not prevent conception if the
people involved do not choose to discipline themselves to “make
it work.”
 If a barrier or foam is neglected or used improperly or if a
woman doesn't take the pills on schedule, a baby is a likely
outcome.
 Birth control methods that permanently make reproduction
impossible are called sterilization, and include things like
vasectomy, tubal ligation, and hysterectomy.

Abortifacients
 some birth control methods like IUDs and some drugs prevent an
already-fertilized and growing embryo from implanting in the uterus, thus
are abortifacients, agents that cause abortions.
 RU-486 is specifically meant to kill an unborn baby, and must be taken
in conjunction with other drugs that cause uterine contractions to expel
the dead baby.
 Depo-Provera injections works by thinning the endometrium of the
woman’s uterus so that when/if a week-old blastocyst-stage embryo
reaches her uterus, it will have no place to implant, and will, thus, die.
 While some people feel that abortion should legally be available as a
means of correcting “mistakes,” it is not a contraceptive and should not
be routinely used as such.
 Legal or not, abortion is not a substitute for personal will power and
responsibility for one’s own actions.
 In early abortions, a suction device is used to dismember and remove
the baby.
 In mid-term abortions, special tongs are used to dismember the baby
and remove the pieces.
 In late-term abortions, some of the amniotic fluid is replaced with a
strong salt solution to try to burn/poison/kill the baby, and the woman is
then given drugs to induce labor.

The most effective contraceptive
method!!!!
The only totally effective method of preventing
making a baby (short of sterilization) is abstinence,
yet in our culture, we’re bringing up a whole
generation of young people who are being taught
that they couldn’t possibly be expected to have the
personal will power and responsibility for their
actions to make that work.
 In previous generations when young people were
taught that they were capable of abstinence and
were expected to abstain from sexual intercourse
until marriage, the rates of teen-age pregnancies
among unwed mothers were much lower.

Menopause
Around 40-50 years of age.
“burning out” of the ovaries – decrease in
estrogens as number of follicles dwindle.
Symptoms
Hot flashes
Dyspnea
Irritability
Fatigue
Anxiety
Decreased strength and calcification of bones

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