Ovarian Cycle Overview

Controlled by: Hypothalamus → Gonadotropin-releasing hormone (GnRH) → Anterior pituitary

→ Secretes FSH (Follicle-Stimulating Hormone) & LH (Luteinizing Hormone).

1.​ FSH's Role:​

○​ Stimulates 15–20 primary follicles to grow.

○​ Rescues primary follicles from degeneration.
○​ Follicles mature, and usually only one becomes dominant.
2.​ Maturation of Follicular Cells:​

○​ Granulosa cells surrounding the oocyte mature due to FSH and GDF-9.
○​ Thecal and granulosa cells produce estrogen.
○​ Estrogen's effects:
■​ Prepares uterine lining (follicular/proliferative phase).
■​ Thins cervical mucus for sperm passage.
■​ Stimulates LH secretion from the pituitary.
3.​ LH Surge & Ovulation:​

○​ LH surge triggers:
■​ Completion of meiosis I by the oocyte.
■​ Initiation of meiosis II, but the oocyte is arrested in metaphase before
ovulation.
■​ Follicular rupture (ovulation) and release of the oocyte.
■​ Progesterone secretion begins (luteinization).

Ovulation

●​ Before Ovulation:​

○​ Secondary follicle reaches a size of 25 mm.

○​ LH surge causes the surface of the ovary to bulge (stigma).
○​ Prostaglandins and local ovarian contractions help ovulate the oocyte.
●​ Clinical Note:​

○​ Middle Pain: Some women experience slight pain during ovulation, usually
mid-cycle.
○​ Basal Temperature Rise: A slight rise in basal body temperature occurs
post-ovulation, which helps track ovulation timing.
 ○​ Ovulation Issues: Some women fail to ovulate due to low gonadotropins, which
can be treated with gonadotropin-stimulating drugs (can lead to multiple
ovulations).

Corpus Luteum Formation & Function

●​ After Ovulation:
○​ Granulosa and theca cells in the ruptured follicle become luteinized and form the
corpus luteum.
○​ The corpus luteum secretes progesterone to prepare the uterine lining for
potential embryo implantation.
○​ If pregnancy does not occur, the corpus luteum degenerates into the corpus
albicans, progesterone decreases, and menstruation begins.
○​ If pregnancy occurs, hCG (human chorionic gonadotropin) prevents the corpus
luteum from degenerating, and it forms the corpus luteum of pregnancy,
maintaining progesterone production until the placenta takes over after the 3rd
month.

Oocyte Transport

●​ Before Ovulation:
○​ The fimbriae (finger-like projections of the oviduct) sweep over the ovary, moving
the oocyte into the oviduct (fallopian tube).
○​ Ciliary action in the tube helps transport the oocyte toward the uterine cavity,
taking about 3-4 days.

Fertilization Process

●​ Location: Fertilization typically occurs in the ampullary region of the uterine tube.
●​ Sperm Journey:
○​ Sperm Viability: Sperm can survive for several days in the female tract.
○​ Movement to Oocyte: Only 1% of sperm reach the oviduct. The rest help in
penetrating the barriers around the egg.
○​ Sperm Capacitation: The sperm undergo a 7-hour conditioning process in the
female tract.
○​ Acrosome Reaction: Capacitated sperm bind to the oocyte's zona pellucida
(outer layer), triggering the acrosome reaction. Enzymes like acrosin allow
sperm to penetrate the zona.
Phases of Fertilization

1.​ Phase 1: Penetration of the Corona Radiata:​

○​ 200-300 million sperm are deposited, but only 300-500 reach the fertilization
site.
○​ Capacitated sperm pass through corona cells to reach the oocyte.
2.​ Phase 2: Penetration of the Zona Pellucida:​

○​ Sperm bind to ZP3 (zona protein) on the zona pellucida, triggering the acrosome
reaction.
○​ Acrosin helps sperm penetrate the zona and reach the oocyte membrane.
3.​ Phase 3: Fusion of Sperm and Oocyte Membranes:​

○​ Sperm binds to the oocyte membrane, leading to fusion.

○​ Zona Reaction: Lysosomal enzymes from the oocyte alter the zona, preventing
other sperm from entering.

Key Takeaways

●​ Ovarian Cycle: Controlled by FSH & LH, leading to ovulation and corpus luteum
formation.
●​ Ovulation & Clinical Significance: Mid-cycle pain (middle pain), temperature rise, and
the risk of multiple pregnancies with fertility drugs.
●​ Fertilization: Involves sperm capacitation, acrosome reaction, and zona penetration,
with only one sperm fertilizing the egg.

Phase 3: Fusion of the Oocyte and Sperm Cell Membranes

1.​ Initial Sperm-Oocyte Interaction:​

○​ Integrins on oocyte bind with disintegrins on sperm.

○​ Fusion occurs after the sperm head's acrosomal membrane disappears, joining
the oocyte membrane with the sperm's posterior head membrane.
2.​ Entry of Sperm into Oocyte:​

○​ Head & tail of sperm enter the oocyte, leaving the sperm membrane on the
oocyte surface.
3.​ Oocyte's Response After Sperm Entry:​
 ○​ Cortical and Zona Reactions:
■​ Cortical granules release enzymes:
■​ Prevents other sperm from entering (prevents polyspermy).
■​ Alters zona pellucida to stop sperm binding.
○​ Resumption of Meiosis:
■​ Oocyte finishes the second meiotic division, forming a female
pronucleus.
■​ The second polar body is formed with minimal cytoplasm.
○​ Metabolic Activation:
■​ Sperm activates the egg for embryogenesis.
4.​ Sperm's Response:​

○​ Male pronucleus forms by swelling of sperm nucleus.

○​ Tail degenerates. Male and female pronuclei merge and lose their nuclear
envelopes.
5.​ DNA Replication and Mitosis:​

○​ Both pronuclei replicate DNA.

○​ Chromosomes align for mitosis, resulting in a diploid zygote.
6.​ Main Results of Fertilization:​

○​ Diploid Chromosome Number: 23 from each parent.

○​ Sex Determination: XX (female) or XY (male).
○​ Cleavage Initiation: Without fertilization, oocyte degenerates after 24 hours.

Contraceptive Methods

1.​ Barrier Methods:​

○​ Male condom (latex, sometimes with spermicide).

○​ Female condom (polyurethane).
○​ Diaphragm, cervical cap, contraceptive sponge.
2.​ Hormonal Contraception:​

○​ Contraceptive Pill: Combination of estrogen and progestin to inhibit ovulation.

○​ Depo-Provera: Progestin injection or implant.
○​ Male Pill: Synthetic androgen, suppresses LH and FSH.
3.​ Intrauterine Device (IUD):​

○​ Prevents pregnancy via effects on sperm, oocytes, or pre-implantation stages.

4.​ RU-486 (Mifepristone):​
 ○​ Used for abortion within 8 weeks.
5.​ Permanent Contraception:​

○​ Vasectomy (males) and Tubal Ligation (females).

Infertility and Treatments

1.​ Infertility Causes:​

○​ Male: Low sperm count, poor motility.

○​ Female: Blocked fallopian tubes, absence of ovulation, hostile cervical mucus.
2.​ In Vitro Fertilization (IVF):​

○​ Stimulates egg production with gonadotropins.

○​ Eggs fertilized outside the body and cultured to the 8-cell stage.
○​ Success rate: 20% (often leads to multiple births).
3.​ Other Techniques:​

○​ GIFT (Gamete Intrafallopian Transfer): Sperm and oocytes placed in fallopian

tubes.
○​ ZIFT (Zygote Intrafallopian Transfer): Fertilized eggs placed in fallopian tubes.
4.​ Intracytoplasmic Sperm Injection (ICSI):​

○​ Single sperm injected into egg for fertilization in cases of severe male infertility.

Cleavage and Early Development

1.​ Cleavage Stages:​

○​ Two-Cell Stage: Zygote divides into smaller blastomeres.

○​ Compaction: Cells maximize contact after the third cleavage.
○​ Morula: 16-cell stage, with inner and outer cell masses.
○​ Blastocyst Formation: Fluid enters, forming the blastocele.
2.​ Morula and Blastocyst:​

○​ Inner cell mass becomes the embryo proper.

○​ Outer cell mass (trophoblast) forms the placenta.

Implantation
 1.​ Trophoblast Invasion:​

○​ Trophoblast cells invade uterine mucosa around day 6.

○​ Integrins and extracellular matrix molecules (like laminin, fibronectin) help
attachment and migration.
2.​ Uterus During Implantation:​

○​ Secretory Phase: Endometrial glands and arteries become coiled and succulent.
○​ Embryo implants in the anterior/posterior uterine wall.

Abnormal Zygotes and Genetic Screening

1.​ Abnormal Zygotes:

○​ 50% of pregnancies end in spontaneous abortion, many due to chromosomal
abnormalities.
2.​ Genetic Screening:
○​ IVF + PCR: Early-stage embryos are screened for genetic defects.
○​ Blastomere removal for DNA analysis.

Uterus Structure and Menstrual Cycle

1.​ Uterus Layers:​

○​ Endometrium: Mucosal lining.

○​ Myometrium: Smooth muscle layer.
○​ Perimetrium: Outer peritoneal covering.
2.​ Menstrual Cycle Phases:​

○​ Proliferative Phase: Under estrogen influence, ovarian follicles grow.

○​ Secretory Phase: After ovulation, under progesterone, uterus prepares for
implantation.
○​ Menstrual Phase: If no pregnancy, endometrium sheds.
3.​ Endometrial Changes:​

○​ Secretory phase: Three layers form (compact, spongy, basal).

○​ If no fertilization: Endometrium sheds, only basal layer remains for regeneration.