Isfahan University of Technology
College of Agriculture, Department of Animal Science
Advanced Reproduction
Physiology
(Part 2)
Prepared by: A. Riasi
http://riasi.iut.ac.ir
Oogenesis & Folliculogenesis
Overview
1: ovary, 2: tertiary follicle, 3: proper ovarian ligament,
4: fallopian tube, 5: ovarian artery and vein
Overview
Overview
Overview
Overview

The ovaries have two distinct functions:


Producing the sex steroids and protein hormones

Prepare the vagina and fallopian tubes to assist in fertilization

Prepare the lining of uterus to accept and implant a zygote

Maintain hormonal support for the fetus before placenta capacity

Act on diverse target organs
Ovogenesis and folliculogenesis

Maintain and nurture the resident oocyte

Mature the oocyte and release it at the right time
The biology of oogenesis

Primordial germ cells migrate from the yolk sac

The primordial germ cells proliferate by mitosis to
form primary oocytes:

In cattle, the first meiotic prophase in days 75-80

The first meiotic division is not completed befor ovulation
The biology of oogenesis

In contrast the male, the female cannot manufacture
new oogonia

It must function with continuously declining number of
primary oocytes.
Folliculogenesis

The first stage of development of the ovarian follicle
parallels the prophase of the oocyte.

As an oocyte enters meiosis, it induces a single layer
of spindle cells to surround it completely.

Cytoplasmic processes from these cells attach to the plasma
membrane of the oocyte.
Folliculogenesis

In the next phase, the spindle-shaped cells become
cuboidal and granulosa cells and a primary follicle is
formed.

Then secondary follicle is created.

After that the zona pellucida is formed.
Folliculogenesis
Folliculogenesis

During the initial deposition of zona pellucida
material some changes occur in oocyte:

Formation of cortical granules within the oocyte cytoplasm

Onset of oocyte RNA synthesis

Gonadotrophin responsiveness
Folliculogenesis

Primordial, primary and secondary follicles appear in
the fetal ovary on Days 90, 140 and 210, respectively
(Russe, 1983).

The second stage of follicular development is take
place during in postnatal and in puberty.
Folliculogenesis

Follicular growth in prepubertal heifers occurs in
waves.

Each wave is preceded by a peak in serum FSH
concentrations (Fortune, 2004).

There is a marked but transient increase in blood
concentrations of both LH and FSH.
Folliculogenesis

From 30-80 days before the first ovulation, the LH
pulses frequency result:

Increases in follicle diameter

Increase in serum estradiol concentrations

Enhancing antral follicle development
Folliculogenesis

The transition to the tertiary follicle includes:

Development of the theca interna and externa

Formation of basal lamina

Formation of cumulus cells

Formation of a fluid-filled antral cavity
Folliculogenesis

The fluid in the antrum contains different chemicals:

Mucopolysachrides

Plasma proteins

Electrolytes

Glycosoaminoglycans

Proteoglycans

Gonadal steroid hormones

FSH, Inhibin and other factors
Folliculogenesis
Folliculogenesis
Folliculogenesis

The final stage of follicular development occurs only
in the postpubertal reproductive ovary.

Some event in third stage:

The granulosa cells spread apart

The cumulus oophorus loosens

The follicle generally ruptures, releasing the oocyte with
adherent cumulus oophorus

At this time the initial meiotic division complete
Follicular waves

Follicles develop in waves.

Emergence of a new follicular wave is preceded by a
rise in FSH.

Suppression of FSH prevents further growth of 3-5
mm follicles.
Follicular waves

The FSH surge peaks, on average, when the largest
follicle is about 5 mm.

Rather than selection of a dominant follicle, selection
involves an action against the other follicles in the
wave (Ginther et al, 2003).
Follicular waves

A subordinate follicle remains viable for at least 1 day
after deviation starts

Administration of FSH when a dominant follicle is
present does not consistently hasten emergence of the
next wave
Follicular waves

With decreasing serum FSH concentrations, follicles
begin to undergo changes:

Reduced production of estrogens

Reduced levels of higher molecular weight (MW) inhibins

Increased amounts of lower MW insulin-like growth factor
(IGF)-binding proteins

Culminating in granulosa cell apoptosis
Follicular waves

FSH stimulates the production of estradiol, activin-A
and inhibin-A (Glister et al, 2001).

These FSH-stimulated factors have intrafollicular
roles in deviation.

Both estradiol and inhibin act alone (as well as
synergistically) to suppress blood FSH concentrations.
Follicular waves

The estradiol secretion by dominant follicle increase
the expression of genes in granulosa cells for:

Aromatase

3-beta-HSD

Receptors for FSH and LH
Follicular waves
Follicular waves
Follicular Size
Progesterone
Atresia
Dominance
Selection
Recruitment
Ovulation
9
16
Day After Ovulation
21
Follicular waves
Follicular waves
 The
IGF system is involved in cell growth and
differentiation and consists of:

IGF-1

IGF-2

IGF receptors

A family of binding proteins (IGFBPs)

IGFBP proteases
Follicular waves

It appears that pregnancy-associated-plasma protein-A
(PAPP-A) is the earliest change detectable in the
future dominant follicle.

PAPP-A is a protease and increase intrafollicular IGFI concentrations.
Follicular waves

Increased IGF-I acts together with FSH to increase
estradiol synthesis.

It is noteworthy that estradiol stimulates the
production of IGF-1 and IGF-1 stimulates the
production of estradiol.
Follicular waves

In the early estrogenic follicle some changes occur for
receptors:

The mRNAs for the FSH receptor and aromatase are
elevated within the granulosa layer.

Theca cells have increased abundances of LH receptor and
17α-hydroxylase.
Follicular waves
Two cell, two-gonadotropin theory of ovarian steroidogenesis
Follicular waves

Dynamic changes are evident within the inhibin
family:

In estrogen-active follicle the large molecular weight
inhibins (i.e., >160 kDa) are elevated.

In estrogen-inactive follicles the smaller inhibins (32 to 34
kDa) are increased.
Follicular waves


FSH secretion by pituitary gland will reduce by:

The increased secretions of estradiol

The increased secretion of large MW inhibin
Lack of FSH prevents further growth of subordinate
follicles, which are also nonestrogenic due to low
concentrations of free IGF-I.
Follicular waves

Once the dominant follicle reaches 10 mm its
granulosa cells begin to express LH receptors.

Continued growth and dominance of the dominant
follicle beyond10 mm appears to be dependent upon
LH secretion.
Follicular waves
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Ovarian follicular and corpus luteum development correlated with endocrine
changes during the bovine estrous cycle. E2 = Estradiol; IGFBP-4 and -5 = insulinlike growth factor binding proteins 4 and 5; OvF = ovulatory follicle.
Follicular waves

Dominant follicles continue to grow for a few days
after selection.

If there is an LH surge the dominant follicle continues
to grow and the oocyte within undergoes:

Final maturation

Culminating in follicle rupture

Ovulation
Follicular waves

Final maturation includes:

Expansion of the cumulus cover

Disruption of the contact between the corona radiata cells
and the oocyte membrane

Perivitelline space formation

Increase lipid content in oocyte cytoplasm

Decrease golgi compartment in oocyte cytoplasm
Follicular waves

Final maturation includes:

The cortical granules are aligned just inside the oocyte
membrane

The chromosomes condense and progress through the final
stages of meiosis I and arrest at metaphase of meiosis II
Follicular waves

The peak and average plasma concentrations of FSH
and inhibin A are lower in the two non-ovulatory
waves than a three-wave cycle
Follicular waves

Higher fertility in three-wave cycles could be due to:

A shorter interval for development of the ovulatory follicle
(Townson et al, 2002).

Delayed regression of the corpus luteum.
Progesterone
Follicular Size
Atresia
Recruitment
Dominance
Ovulation
Selection
FSH Sensitive Pool
Ovulation
9
16
Day After Ovulation
21
Ovulation

Ovulation takes place about 10-14 hours after the end
of oestrus.

The gonadotropin surge is important for ovulation:

Increase progesterone production

Increase estrogen production

Increase prostaglandins (PGE2 & PGF2α)
Corpus luteum formation

In
its
early
stages
of
growth
the
corpus
haemorrhagicum is difficult to palpate.

The corpus luteum (CL) is palpable at about five
days post ovulation.
Corpus luteum formation


It frequently has a distinct crown:

About ½ cm in diameter

About ½ cm high
The corpus luteum enlarges progressively to two to
three cm by day-8 or 9 and has a liver like
consistency.
Corpus luteum formation

Actually the CL is made up two cell groups:

The large luteal cells, which originated from granulosa
cells.


The small luteal cells which originated from theca cells.
The luteal cells are steroidogenic and secrete
progesterone.
Corpus luteum formation

Progesterone has the following functions during
pregnancy:

It prevents the cow from coming on heat.

The function of the hormone oxytocin is blocked.

It regulates the changes in the mucous membranes in the
uterus.

It plays a role in the formation of udder tissue.
Some research papers associated to this lecture
1.
Beg, M. A. et al. 2002. Follicle Selection in Cattle: Dynamics of follicular
fluid factors during development of follicle dominance. Biology of
Reproduction. 66: 120–126.
2.
Bisinotto, R. S. Et al. 2010. Follicular wave of the ovulatory follicle and
not cyclic status influences fertility of dairy cows. J. Dairy Sci. 93 :3578–
3587.
3.
Rýfat, M. et al. 2005. Evaluation of the corpus luteum size throughout
the cycle by ultrasonography and progesterone assay in cows. Turk. J.
Vet. Anim. Sci. 29: 1311-1316.