Human Fertilization

Fertilization is the biological process of fusion of male and female gametes resulting in the formation of a zygote.

The term “fertilisation” (from the Latin fertilis, which means “to bear”) refers to the joining of the cytoplasm and
pronuclei of the male and female gametes.

Steps in fertilization:-

1. Male discharges the semen into the vagina of the female during copulation (coitus).
2. Preparation of the Sperm:-
Ejaculated sperm are not ready to fertilize an egg when they enter the vagina. In response to the dilution
of semen in the vagina, they undergo several changes, which are collectively known as capacitation.
Capacitation- Capacitation occurs after ejaculation, when Albumin proteins, present in the female
reproductive tract dissolve the sperm’s cholesterol coat. This initiate few changes-
 1.Intracellular Ca++ levels increase.
 2.Spermatic motility is activated and tails change beat frequency.
 3.Sperm cell surface antigens are lost. The loss of these proteins renders the sperm more receptive
to binding to the egg.
3. Sperm-Egg Binding:-
 In humans the process of sperm-egg binding is not so simple. The complicating factor is the thick
zona pellucida, which keeps sperm from binding close to the egg plasma membrane.
 The zona pellucida glycoprotein III(ZPGP) could prevent sperm binding to eggs showing that ZPGP III
is the sperm receptor on egg. The carbohydrate groups on the zona pellucida glycoproteins function
as sperm receptors.
 Similarly galactosyl transferase and other proteins of sperm helps in binding with ZPGPIII to facilitate
the binding.

4. Acrosome reaction :-
 As a result of irreversible binding of the sperm to the egg, the zona pellucida triggers the acrosome
reaction. The outer plasma membrane of the acrosome fuses at multiple sites with the plasma
membrane and the
 contents of the acrosome are released.
 Two of the important components are
 acrosin (a serine protease)= Acrosin bores a hole in the zona pellucida so that the sperm can reach
the egg itself.
 N-acetylglucoaminidase= hydrolyzes the O-linked oligosaccharides in ZPGP III to allow the sperm to
detach.
 As a result of the membrane fusion, a new surface is exposed on the sperm the inner acrosomal
membrane.

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N.B- Sperm that lose their acrosomes before encountering the oocyte are unable to bind to the zona pellucida and
thereby unable to fertilize. Assessment of acrosomal integrity of ejaculated sperm is commonly used in semen
analysis.

5. Penetration of the Zona Pellucida:-

 The constant propulsive force from the sperm's flagellating tail, in combination with acrosomal
enzymes, allow the sperm to create a tract through the zona pellucida.
 These two factors - motility and zona-digesting enzymes- allow the sperm to traverse the zona
pellucida.
 Some investigators believe that sperm motility is of overriding importance to zona penetration,
allowing the knife-shaped mammalian sperm to basically cut its way through the zona pellucida.
6. Sperm-Oocyte (egg) Binding:-
 Once a sperm penetrates the zona pellucida, it binds to and fuses with the plasma membrane of the
oocyte.
 Binding occurs at the posterior (post-acrosomal) region of the sperm head.
 A leading candidate in some species is a dimeric sperm glycoprotein called fertilin, which binds to a
protein in the oocyte plasma membrane and may also induce fusion.
 Interestingly, humans and apes have inactivating mutations in the gene encoding one of the subunits
of fertilin, suggesting that they use a different molecule to bind oocytes.
7. Fusion of male and female pronucleus:-
 Once the sperm fuses with the egg, the beating of the tail stops immediately.
 The sperm instead is drawn into the egg by elongation and fusion of the egg’s microvilli.
 As a result, the sperm nucleus and other organelles are incorporated into the egg cytoplasm.
 The sperm nucleus undergoes a series of changes, including chromatin decondensation and
formation of a new nuclear envelope, to form a male pronucleus.
 The male pronucleus uses microtubules to migrate to the center of the cell, where it fuses with the
female pronucleus to reconstitute a diploid nucleus.
 Other sperm organelles (e.g., mitochondria) persist during early cleavage stages of the embryo and it
is conjectured that they may play a role in development.
8. Activation - The Egg’s Response:-
Prior to fertilization, the egg is in a quiescent state, arrested in metaphase of the second meiotic division.
Upon binding of a sperm, the egg rapidly undergoes a number of metabolic and physical changes that
collectively are called egg activation.
 The immediate events after fertilization include the egg’s effort to prevent polyspermy.
 Polyspermy refers to the fertilization of the egg by more than one sperm, resulting in zygotes with
greater than a diploid amount of DNA.
 This causes early embryonic defects and arrest of development. After sperm-egg fusion, the egg
mounts the cortical reaction to prevent polyspermy.
cortical reaction-
 The cortical reaction refers to a massive exocytosis of cortical granules seen shortly after sperm-
oocyte fusion.
 Cortical granules contain a mixture of enzymes, including several proteases, which diffuse into the
zona pellucida following exocytosing their contents into the perivitelline space (the space
between the plasma membrane and the zona pellucida)..
 These proteases alter the structure of the zona pellucida, inducing what is known as the zona
reaction.
 Components of cortical granules may also interact with the oocyte plasma membrane.

zona reaction - The zona reaction refers to an alteration in the structure of the zona pellucida catalyzed by proteases
from cortical granules. The critical importance of the zona reaction is that it represents the major block to

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polyspermy in most mammals. Characterized by (a) The zona pellucida hardens (b) Sperm receptors in the zona
pellucida are destroyed.

Fig: Cortical Reaction

Overview of fertilization

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