Fertilization

Process of fertilization

Ass. Prof. Dr. Malak A. Al-yawer

Fertilization Includes those mechanisms whereby:

A sperm approaches to
Becomes attached to and then penetrates the surface of an ovum
The early series of changes which follow

Female Reproductive system

Sperm transport

vagina
Site of sperm’s deposition


Cervix
Only 1% of sperm deposited in the vagina enter the cervix, where they may survive for many hours.
consistency and viscosity of cervical mucus , under hormonal control , play an important role in the process of fertilization.
Prior to ovulation – watery cervical mucus luteal phase – viscous and disorganized cervical mucus

Uterus

• primarily by their own propulsion and
• may be assisted by movements of fluids created by uterine cilia.
The trip from cervix to oviduct requires a minimum of 2 to 7 hours

Oviduct

Uterotubal junction a significant barrier

after reaching the isthmus, sperm become less motile and cease their migration

Oviduct Capacitation

It is a period of conditioning in the female reproductive tract , associated with
1.removal of glycoprotein coat and seminal plasma proteins from the plasma membrane that overlies the acrosomal region of the spermatozoa.
2. reorganization of plasma membrane lipids and proteins to prepare the sperm for acrosome reaction .
Much of this conditioning occurs in the uterine tube
In the human, it lasts approximately 7 hours .
Sperm can be capacitated by incubation in certain fertilization media.

Oviduct Oocyte transport

• Shortly before ovulation, fimbriae of the uterine tube sweep over the surface of the ovary, and the tube itself begins to contract rhythmically.
• It is thought that the oocyte surrounded by some granulosa cells is carried into the tube by
• the sweeping movements of the fimbriae and
• by motion of cilia on the epithelial lining.
• Once in the tube, cumulus cells withdraw their cytoplasmic processes from the zona pellucida and lose contact with the oocyte.
•

At ovulation, sperm

again become motile, perhaps because of chemoattractants produced by cumulus cells surrounding the egg, and
swim to the ampulla, where fertilization usually occurs.

The oviduct provides the appropriate environment not only for fertilization but for early embryonic development ( the embryo remain there for a period of 3 days ) .

The fertilizable lifespan of gametes

The oocyte can be fertilized for up 24 h after ovulation
some sperm cells remain viable in the female reproductive tract for up to 6 days although most of them have degenerated after 24h
For fertilization to occur successfully, sexual intercourse must, therefore, occur between 5 days before and one day after ovulation .


Attaching & penetrating the surface of an ovum by capacitated sperm

Attaching & penetrating the surface of an ovum by capacitated sperm

1. penetration of the corona radiata

2. penetration of the zona pellucida
3. sperm-oocyte binding

1. penetration of the corona radiata

The corona radiata is a barrier to the sperm cells reaching the oocyte .

The sperm cells are propelled through the loose matrix between the follicular cells of corona radiata by the action of their flagella.
Of the 200 to 300 million spermatozoa deposited in the female genital tract, only 300 to 500 reach the site of fertilization. Only one of these fertilizes the egg.
Only capacitated sperm pass freely through corona cells


2. penetration of the zona pellucida
The zona pellucida is an extracellular membrane , comprised mostly of glycoproteins, between corona radiata and the oocyte
One particular zona pellucida glcoprotein called zp3 which is species –specific sperm cell receptor to which molecules on the acrosomal cap of the sperm cell bind .
This binding initiates the acrosomal reaction

The acrosome reaction

Occurs after binding to the zona pellucida,
is induced by zona proteins.
culminates in the release of enzymes needed to penetrate the zona pellucida, including acrosin- and trypsin-like substances.

3. Fusion of the Oocyte and Sperm Cell Membranes

The initial adhesion of sperm to the oocyte is mediated in part by the interaction of integrins on the oocyte and their ligands, disintegrins, on sperm.
Because the plasma membrane covering the acrosomal head cap disappears during the acrosome reaction, actual fusion is accomplished between the oocyte membrane and the membrane that covers the posterior region of the sperm head.
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.

Polyspermy

• penetration of more than one spermatozoon into the oocyte


Prevention of polyspermy
• Fast block to polyspermy
• Slow block to poly spermy

Fast block to polyspermy

Once the first sperm cell attaches to the integrin (alpha 6 beta 1) on the surface of the oocyte plasma membrane, depolarization of the oocyte plasma membrane occurs within 2-3 seconds.
This depolarization( fast block to poly spermy) prevents additional sperm from attaching to the oocyte plasma membrane .

Slow block to poly spermy

Depolarization causes the intracellular release of ca+2 , which in turn causes the exocytosis of water and other molecules from secretory vesicles referred to as cortical granules on the inner surface of the oocyte plasma membrane
The released fluid causes the oocyte to shrink and the zona pellucida to denature and expand away from the oocyte .
As a result of denaturation of the zona pellucida , zp3 is inactivated and no additional sperm cells can attach . This reaction is referred to as the slow block to poly spermy

The early series of changes which follow “ egg activation “

The early series of changes which follow “ egg activation “
Prior to fertilization , the egg is in a quiescent state . Upon binding of a sperm ,the egg rapidly undergoes a number of metabolic and physical changes collectively called “ egg activation “
Cortical and zona reactions
Resumption of the second meiotic division
Metabolic activation of the egg –The activating factor is probably carried by the spermatozoon.


Oocyte immediately after ovulation,

The main results of fertilization

Restoration of the diploid number of chromosomes, , 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. Hence, the chromosomal sex of the embryo is determined at fertilization.
• Initiation of cleavage.

Clinical correlates

Contraceptive Methods

Contraceptive Methods

Barrier techniques of contraception include

the male condom, and
the female condom

Prevention of ovulation

The contraceptive pillis a combination of estrogen and the progesterone which together inhibit ovulation but permit menstruation.

Depo-Provera is a progestin compound that can be implanted subdermally or injected intramuscularly to prevent ovulation for up to 5 years or 23 months.

A male “pill”

has been developed and tested in clinical trials.
It contains a synthetic androgen that prevents both LH and FSH secretion
It either
stops sperm production (70% to 90% of men) or
reduces it to a level of infertility.


The intrauterine device (IUD)
is placed in the uterine cavity.
Its mechanism for preventing pregnancy is not clear but may entail direct effects on sperm and oocytes or inhibition of preimplantation stages of development.

Vasectomy and tubal ligation

are effective means of contraception, and
both procedures are reversible, although not in every case.

Infertility

Infertility is a problem for 15% to 30% of couples.
Male infertility
Infertility in a woman
may be a result of insufficient numbers of sperm and/or poor motility.
Normally, the ejaculate has a volume of 3 to 4 mL, with approximately 100 million sperm per milliliter.


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)

is a group of fertility treatments that involve both the sperm and the egg.

Assisted reproductive technology (ART)

In vitro fertilization (IVF)
intracytoplasmic sperm injection (ICSI)
gamete intrafallopian transfer (GIFT)
zygote intrafallopian transfer (ZIFT).

In vitro fertilization (IVF)

is the most common type of ART.
the sperm fertilizes the egg outside the body, and doctors implant it into the woman's uterus in hopes of a successful pregnancy.
IVF cycle takes four to six weeks to complete and usually costs about $12,000

There are five steps in the IVF treatment cycle

• Ovarian stimulation.
• Egg retrieval
• Insemination
• Fertilization and embryo culture
• Embryo transfer

In vitro Fertilization ( IVF )

The risk of producing malformed offspring by in vitro procedures is low.
A disadvantage of IVF is its low success rate
because preimplantation-stage embryos are resistant to teratogenic insult,

only 20% of fertilized ova implant and develop to term.

Therefore, to increase chances of a successful pregnancy, four or five ova are collected, fertilized, and placed in the uterus. This approach sometimes leads to multiple births.

The following methods of ART require patent uterine tubes.

Gamete intrafallopian transfer (GIFT)
zygote intrafallopian transfer (ZIFT)
introduces oocytes and sperm into the ampulla of the fallopian (uterine) tube, where fertilization takes place.

fertilized oocytes are placed in the ampullary region.

Intracytoplasmic sperm injection ICSI))
(oligozoospermia) or even (azoospermia), can be overcome by using intracytoplasmic sperm injection (ICSI).

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.

Thank you

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