Detailed Notes on Developmental Biology and Gonad Development

Learning Objectives

• Grasp the timeline of embryo development.
• Comprehend the genetic and endocrine control of sexual development.
• Understand the connection between gonadal development and meiotic timing: why men remain fertile for life while women have a limited reproductive span.

Embryo Development Timeline

• Day 1: Fertilization occurs, forming a zygote.
• Day 2: Cleavage begins (cell division).
• Day 3: Compaction of cells takes place.
• Day 4: Differentiation of cells into various cell types.
• Day 5: Cavity formation (cavitation).
• Day 6: Zona hatching occurs, allowing the embryo to prepare for implantation.
• Day 7: Implantation into uterine lining.
• Day 9-12: Formation of bilaminar disc (ectoderm and endoderm) and mesoderm formation.
• Day 18-23: Development of amniotic sac and further differentiation of the fetal structures.

Developmental Stages and Teratogenic Effects

• Embryonic Period (Weeks 1-8): High susceptibility to teratogens resulting in major morphologic abnormalities (CNS, heart, eyes, teeth, palate).
• Fetal Period (Weeks 9-38): Lower susceptibility to teratogens; physiological defects and minor morphologic changes can occur.

Endocrine Control of Sexual Development

• Endocrine Differences: Males have higher testosterone levels from Leydig cells in the testes, while females produce smaller amounts.
• Castration Impact: Changes the development of secondary sexual characteristics.
• Historical Contributions: Arnold Berthold (1849) and Charles-Édouard Brown-Séquard (1856) made key discoveries about hormones influencing sexual development.

Gonadal Development

• Indifferent Stage: Early embryos possess undifferentiated gonads; potential to develop into either ovaries or testes.
• Male Development: Wolffian duct develops into male structures (epididymis, vas deferens) while Mullerian duct regresses.
• Female Development: Mullerian duct develops into the Fallopian tubes, uterus, and vagina while Wolffian duct regresses.

Hormonal Influence on Sexual Differentiation

• Anti-Müllerian Hormone (AMH): Produced by Sertoli cells in developing testes; responsible for regression of Mullerian ducts during male differentiation.
• Testosterone: Promotes the development of Wolffian duct structures.

Genetic Sex Determination

• SRY Gene: Located on the Y chromosome, acts as a master switch for male differentiation; without SRY, embryonic structures default to female development.
• Turner Syndrome (XO) and Klinefelter Syndrome (XXY): Examples of chromosomal abnormalities affecting sexual development (females with short stature, males with infertility).

Meiosis and Fertility

• Timing Differences: Males undergo meiosis at puberty, beginning sperm production, while females are born with a set number of oocytes that decline over time.
• Retinoic Acid (RA) and Meiosis: RA signaling drives germ cells to undergo meiosis in females; in males, a barrier prevents meiosis until puberty.

Key Takeaways

• Gonadal Development Timing: Males differentiate early (first trimester), while females differentiate later. This sexual differentiation complexity indicates that female development is not passive but rather requires regulation.
• Role of AMH and Testosterone: These hormones drive differentiation in male embryos while preventing female structure development, confirming the critical role of hormonal signaling in determining sex.