First Week of Development Ovulation to Implantation pdf - نظري

Chapter 3

First Week of

Development:

Ovulation to

Implantation

OVARIAN CYCLE

• At puberty,
• sexual cycles
• Hypothalamus: Gonadotropin releasing hormone (GnRH),
• pituitary gland 

gonadotropins

– (follicle-stimulating hormone (

FSH

) and

– luteinizing hormone (

)),

– stimulate and control cyclic changes in the ovary.

• 15 to 20 primary-stage (preantral)

follicles are stimulated to grow
under the influence of FSH. (FSH
rescues 15 to 20 of these cells
from a pool of continuously
forming primary follicles)

• only one of these follicles reaches

full maturity, and only one oocyte
is discharged;

• the others degenerate and

become

atretic

(the oocyte and

surrounding follicular cells
degenerate and are replaced by
connective tissue, forming a

corpus atreticum

)

FSH effect on granulosa cells

• FSH

also stimulates maturation of follicular (

granulosa

) cells surrounding the oocyt

• In turn, proliferation of these cells is mediated by

growth differentiation factor 9

, a

member of the

transforming growth factor-β (TGFβ) family

Formation & secretion of estrogens

• FSH stimulates theca interna cells & granulosa cells to secrete estrogens

during the follicular stage

• In cooperation,

theca interna and granulosa

cells produce

estrogens:

– Theca interna cells produce androstenedione & testosterone
– Granulosa cells convert these hormones to estrone & estradiol

ESTROGEN EFFECT

The uterine endometrium enters the follicular or proliferative phase;

Thinning of the cervical mucus occurs to allow passage of sperm; and

The anterior lobe of the pituitary gland is stimulated to secrete LH.

LH surge

• At midcycle, there is an LH surge that:
• Elevates concentrations of maturation-

promoting factor, causing oocytes to
complete meiosis I and initiate meiosis
II;

• Stimulates production of progesterone

by follicular stromal cells (luteinization);
and

• Causes follicular rupture and ovulation.

Stages of growth

of ovarian

follicles

Ovulation

• Seconday follicle: diameter of 25 mm.

• abrupt increase in LH

that causes the primary oocyte to complete meiosis I

and the follicle to enter the preovulatory stage.

• Meiosis II is also initiated, but the oocyte is arrested in metaphase

approximately 3 hours before ovulation.

• an avascular spot, the

stigma,

appears.

• LH increases

collagenase

activity

• Prostaglandincause

local muscular contractions in the ovarian wall.

• OVULATION

: release of oocyte, which together with its surrounding

granulosa cells from the region of the cumulus oophorus,

• coronaradiata

Clinical Correlates - Ovulation

• Mittelschmerz “middle pain” : mid-cycle pain
• Rise in basal temperature with ovulation.
• Failure of ovulation: low concentrations of gonadotropins: - administration

of drugs to stimulate gonadotropins

Corpus Luteum

• LH lutein cells in corpus luteum progesterone secretory phase of endometrium

Oocyte transport

Corpus Albicans

• If fertilization does not occur, the corpus luteum reaches maximum development

approximately 9 days after ovulation, then degenerates

• forms a mass of fibrotic scar tissue, the

corpus albicans.

• Simultaneously, progesterone production decreases, precipitating menstrual

bleeding.

• If the oocyte is fertilized, degeneration of the corpus luteum is prevented by human

chorionic gonadotropin

(hCG),

a hormone secreted by the developing embryo.

• The corpus luteum continues to grow and forms the

corpus luteum of pregnancy

• secrete progesterone until the end of the fourth month;
• progesterone by the trophoblastic component of the placenta becomes adequate

for maintenance of pregnancy.

• Removal of the corpus luteum of pregnancy before the fourth month usually leads

to abortion.

Fertilization

• Fertilization, the

process by which male

and female gametes

fuse,

• occurs in the

ampullary region

the uterine tube.

• Spermatozoa may

remain viable in the

female reproductive

tract

for several days.

• Only 1% of sperm

deposited in the

vagina enter the

cervix, where they

may survive for many

hours.

• Spermatozoa

are not

able to fertilize the oocyte immediately upon arrival in the

female genital tract but must undergo

• (1) capacitation and
• (2) acrosome reaction

Capacitation

• is a period of conditioning

in the female reproductive tract

that in the

human lasts approximately

7 hours.

• During this time, a

glycoprotein coat and seminal plasma proteins

are

removed from the plasma membrane that overlies the acrosomal region
of the spermatozoa.

• Only capacitated sperm can pass through the corona cells and undergo the

acrosome reaction.

The acrosome reaction

• which occurs after binding to the zona

pellucida,

• is

induced by zona proteins.

• This reaction culminates in the release of

enzymes needed to penetrate the zona
pellucida, including

acrosin- and trypsin-

like substances

The phases of fertilization

• phase 1

, penetration of the corona radiata;

 Capacitated sperm pass freely
 Of the 200 to 300 million spermatozoa normally deposited in the female genital

tract, only 300 to 500 reach the site of fertilization.

 Only one of these fertilizes the egg.

• phase 2

, penetration of the zona

pellucida;

Both binding and the acrosome reaction are
mediated by the ligand

ZP3

, a zona protein.

zona reaction

: to prevent sperm penetration

• phase 3

, fusion of the oocyte and

sperm cell membranes

In the human, both the head and tail of the
spermatozoon enter the cytoplasm of the oocyte,
but the plasma membrane is left behind on the
oocyte surface.

As soon as the spermatozoon has entered the oocyte, the egg responds in three ways:

• 1. Cortical and zona reactions

 As a result of the release of cortical oocyte granules, which contain lysosomal

enzymes,

 (1) the oocyte membrane becomes impenetrable to other spermatozoa, and
 (2) the zona pellucida alters its structure and composition to prevent sperm binding

and penetration.

 These reactions prevent

polyspermy

(penetration of more than one spermatozoon

into the oocyte).

• 2. Resumption of the second meiotic division.

Finishing of second meiotic division
immediately after entry of the
spermatozoon.
 second polar body + definitive oocyte
Definitive oocyte chromosomes: (22 plus
X) in the
female pronucleus

The spermatozoon, meanwhile, moves
forward until it lies close to the female
pronucleus. Its nucleus becomes
swollen and forms the

male

pronucleus

• 3. Metabolic activation of the egg.

 The activating factor is probably carried by the spermatozoon.
 Activation encompasses the initial cellular and molecular events associated with early

embryogenesis.

Female & male pronuclei

• DNA replication in pronuclei.
• mitotic division.
•  sister chromatids move to opposite poles
• Furrow dividing the cytoplasm into 2 parts

The main results of fertilization

• Restoration of the diploid number of chromosomes

, half from the father

and half from the mother. Hence, the zygote contains a new combination
of chromosomes different from both parents.

• Determination of the sex of the new individual

. An X-carrying sperm

produces a female (XX) embryo, and a Y-carrying sperm produces a male
(XY) embryo. Therefore, the

chromosomal sex of the embryo

determined at fertilization.

• Initiation of cleavage

. Without fertilization, the oocyte usually degenerates

24 hours after ovulation.

Clinical Correlates

Contraceptive Methods

• Barrier techniques
• The contraceptive pill
• Depo-Provera
• A male “pill”
• The intrauterine device (IUD)
• The drug RU-486 (mifepristone) causes abortion if it is administered within

8 weeks of the previous menses.

• Sterilization: Vasectomy and tubal ligation

Infertility causes

• Male infertility

: insufficient numbers of sperm and/or poor motility.

• Normally, the ejaculate has a volume of 2 to 6 mL, with as many as 100 million

sperm per milliliter.

• Men with 20 million sperm per milliliter or 50 million sperm per total ejaculate are

usually fertile.

• Infertility in a woman

may be due to a number of causes, including

– occluded uterine tubes (most commonly caused by pelvic inflammatory disease),
– hostile cervical mucus,
– immunity to spermatozoa,
– absence of ovulation, and others.

Assisted Reproductive Technology (ART).

• In vitro fertilization (IVF)

– Follicle growth in the ovary is stimulated by administration of gonadotropins.
– Oocytes are recovered by laparoscopy from ovarian follicles with an aspirator just

before ovulation when the oocyte is in the late stages of the first meiotic division.

– The egg is placed in a simple culture medium, and sperm are added immediately.
– Fertilized eggs are monitored to the eight-cell stage and then placed in the uterus

to develop to term.

• To increase chances of a successful pregnancy, 4 or 5 ova are collected, fertilized,

and placed in the uterus. This approach sometimes leads to multiple births.

intracytoplasmic sperm injection (ICSI).

• Severe male infertility, in which the ejaculate contains very few live sperm

(oligozoospermia) or even no live sperm (azoospermia), can be overcome
using

intracytoplasmic sperm injection (ICSI).

• With this technique, a single sperm, which may be obtained from any

point in the male reproductive tract, is injected into the cytoplasm of the
egg to cause fertilization.

• The technique carries an increased risk for fetuses to have Y chromosome

deletions but no other chromosomal abnormalities.

Cleavage

• series of mitotic divisions,

increasing the numbers of cells,

blastomeres

compaction

• After the third cleavage,
•

blastomeres

maximize their contact

with each other, forming a compact
ball of cells held together by

tight

junctions

Organization of cells in the morula

• compacted embryo divide again to form a 16-cell morula (mulberry).
• Inner cell mass, embryo proper
• Outer cell mass, trophoblast (placenta).