Oogenesis: Prenatal and Postnatal Stages

• Oogenesis is the process of producing a mature oocyte from immature germ cells.
• It occurs in the ovaries and continues in the oviducts.
• The process starts in early fetal life and continues during puberty.

Prenatal Oogenesis

• Majority of the steps occur prenatally.
• Oogonium divides many times in fetal life through mitosis.
• Oogonia grow before birth to produce primary oocytes.
• Most primary oocytes undergo atresia before birth.
• Females are born with all the primary oocytes they will ever have.
• Primary oocytes do not divide further.
• Primary oocyte starts the first meiosis before birth but stops (arrests) in prophase I until puberty.

Number of Primary Oocytes During Life

• Before birth, there are ~7 million.
• At birth, there are ~2 million.
• Before puberty, there are ~400,000.
• After puberty (during the reproductive phase), there are ~4,000.

Postnatal Oogenesis

• After puberty, GnRH is released from the hypothalamus.
• GnRH causes FSH and LH release
• These hormones control the menstrual cycle, which takes almost 28 days.
• In each cycle, 5-15 primordial follicles start to grow, but only one oocyte gets ready for fertilization.
• Oogenesis is controlled by the menstrual cycle (~28 days).
• After puberty, menstrual cycles begin.
• Oocyte begins meiosis and is arrested in prophase I during fetal life.
• As the menstrual cycle starts, the oocyte completes the first meiotic division.
• It enters the second meiosis and arrests in metaphase II in the menstrual cycle again.
• Meiosis continues if fertilization occurs.

Arrest Points in Oogenesis

• Primary oocyte is arrested in diplotene of prophase I.
• It completes meiosis I and enters into meiosis II.
• Secondary oocyte is arrested in metaphase II until activation or fertilization, which results in a mature egg.

Folliculogenesis

• Oocyte development occurs within follicles.
• Folliculogenesis is the development of follicles.
• Follicles are sac-like structures where oocytes grow.
• Oogenesis and folliculogenesis occur in conjunction with each other.

Ovarian Follicles

• Ovarian follicles' primary role is oocyte support.
• From birth, the ovaries contain numerous immature, primordial follicles.
• These follicles each contain an immature primary oocyte.
• After the first menstruation, a clutch of follicles begins folliculogenesis.
• An ovarian follicle consists of an oocyte surrounded by one or more layers of epithelial cells.
• The follicles formed during fetal life are primordial follicles, consisting of a primary oocyte (2N) arrested in prophase I enveloped by a single layer of flattened follicular cells.
• These follicles are in the ovarian cortex.
• The oocyte in the primordial follicle is ~25 µm in diameter and contains chromosomes in the first meiotic prophase.
• The basal lamina surrounds the follicular cells.
• It forms a clear boundary between the follicle and the vascularized stroma.
• With the release of follicle-stimulating hormone (FSH) from the pituitary, a small group of primordial follicles begins folliculogenesis each month.
• This involves the growth of the oocyte (meiosis continues), proliferation, and changes in the follicular cells and stromal fibroblasts around each follicle.
• An oocyte can grow to a diameter of about 120 µm.
• Follicular cells undergo mitosis and form a simple cuboidal epithelium around the growing oocyte.
• The follicle is called a unilaminar primary follicle.
• Follicular cells continue proliferating, forming a stratified follicular epithelium called the granulosa which communicates through gap junctions.
• Follicular cells are now termed granulosa cells.
• The follicle becomes a multilaminar primary follicle surrounded by a basement membrane.

Zona Pellucida

• Between the oocyte and the first layer of granulosa cells, extracellular material accumulates, called the zona pellucida.
• The zona pellucida contains four glycoproteins secreted by the oocyte.
• It is essential for sperm receptors, binding specific proteins on the sperm surface and inducing acrosomal activation.
• A fluid (liquor folliculi) begins to accumulate in the intercellular spaces between granulosa cells.
• Fluid-filled spaces coalesce to form a single large cavity called an antrum.
• As a result of this, secondary follicles are developed.
• Stromal cells outside each growing primary follicle differentiate to form the follicular theca.
• This differentiates further into two distinct tissues around the follicle.
  • A well- vascularized endocrine tissue, the theca interna, with steroid-producing cells secreting androstenedione.
  • A more fibrous theca externa with fibroblasts and smooth muscle merges gradually with the surrounding stroma.
• First meiotic division is completed

Secondary Oocytes

• The chromosomes are equally divided between the two daughter cells, but one retains almost all of the cytoplasm.
• The cell is now the secondary oocyte (1N), and the other becomes the first polar body (PB).
• Secondary oocyte contains half the chromosome number (N) of the parent cell.
• The oocyte begins the second meiotic division but arrests again at metaphase until fertilization.
• Follicular fluid contains hyaluronic acid, growth factors, plasminogen, fibrinogen, the anticoagulant heparan sulfate proteoglycan, and high concentrations of steroids (progesterone, androstenedione, and estrogens) with binding proteins.
• As the antrum develops, the granulosa cells around the oocyte form a small hillock, the cumulus oophorus, which protrudes into the antrum

Graafian Follicle

• Granulosa cells surrounding the zona pellucida make up the corona radiata.
• They accompany the oocyte when it leaves the ovary at ovulation.
• The large antrum of a mature or (preovulatory follicle / graafian follicle) accumulates follicular fluid and expands to a diameter of ~2 cm.
• It contains a secondary oocyte (1N) arrested at metaphase II.
• A preovulatory follicle forms a bulge at the ovary surface visible with ultrasound imaging.
• A mature follicle normally develops from a primordial follicle over a period of about 90 days.

Ovulation

• It's the release of oocyte from the ovary.
• Occurs around the 14th day of a cycle.
• Hours before ovulation, the mature dominant follicle bulging against the tunica albuginea develops an ischemic area, the stigma, in which tissue compaction has blocked blood flow.
• Usually only one oocyte is ovulated during each cycle, but sometimes either no oocyte or two or more oocytes may be expelled.
• Ovulation occurs in response to the LH surge.
• The secondary oocyte and its corona radiata cells leave the ruptured follicle at the ovarian surface to enter the fimbriated end of the oviduct.
• During a menstrual cycle, one follicle becomes dominant and develops farther than the others.
• The dominant follicle undergoes ovulation, while the other follicles undergo atresia.
• Large growing follicles produce estrogen before becoming atretic follicles.
• This estrogen stimulates the preparation of the reproductive tract to transport and sustain the embryo if the oocyte from the dominant follicle is fertilized.

Follicular Atresia

• Most ovarian follicles undergo the degenerative process called atresia. Follicular cells and oocytes die and are disposed of by phagocytic cells..
• Follicles at any stage of development including nearly mature follicles may become atretic.
• Atresia involves apoptosis and detachment of the granulosa cells, autolysis of the oocyte, and collapse of the zona pellucida.
• Atretic follicles are follicles (in various stages of maturation) undergoing degeneration.
• After a graafian follicle ovulates, the remaining secondary follicles degenerate.

Oocyte

• A large cell having the potential to feed the zygote during early mitotic divisions.
• The biggest cell of the body at ~120-130μm.
• It is surrounded by zona pellucida and cumulus oophorus cells.
• Feeds and protects the oocyte.

Fertilization

• The process where sperm and oocyte come together to form a new zygote.
• If fertilization occurs, meiosis II is induced to continue when a sperm penetrates the oocyte.
• Meiosis II finishes, and two cells are produced again.
• The chromatids are divided between the two daughter cells, but again, one of these cells is big (oocyte) ,and smaller become the second polar body.
• The second polar body (PB) is extruded.