2009 BGD-B Lecture Sexual Differentiation

Introduction

This lecture is still available online with links to powerpoint slides as PDF for printing online lecture.

This current page is only in the early developmental stage and not complete.

BGD Genital 2009 Lecture Slides

The links below to PDF versions of lecture slides.

• 1 slide/page (52 pages 1.25 Mb)
• 4 slides/page (13 pages, 803 Kb)
• 6 slides/page (18 pages, 776 Kb)
• Lecture Handout (5 pages 172 Kb)

Lecture Overview

• Gonad
• Internal Genitalia
• Reproductive Tract
• External Genitalia
• Development
• Function
• Abnormalities

Background Reading

UNSW Embryology

• Gonad Development

NIH Bookshelf

• Developmental Biology (Gilbert) Chapter 17
• Endocrinology (Nussey and Whitehead) The Gonad

Textbook References

• Human Embryology (3rd ed.) Larson Chapter 10 pp266-313
• The Developing Human (6th ed.) Moore & Persaud Chapter 13 p303-346
• Before We Are Born (5th ed.) Moore & Persaud Chapter 14 p289-326
• Essentials of Human Embryology, Larson Chapter 10 p173-205
• Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152

Genital System Development

3 stages

1. Differentiation of gonad (sex determination)
2. Differentiation of internal genital organs
3. Differentiation of external genital organs

2nd and 3rd stages dependent on endocrine gonad

• Long Maturation Time-course
  • Begins in embryo
  • Continues through fetal
  • Finishes in puberty

Sex Chromosomes

X Chromosome

• 1400+ genes
• 150 million base pairs
• 95% determined

Y Chromosome

• 200+ genes
• 50 million base pairs
• 50% determined

Sex Determination

• Humans (week 5-6)
  • Germ cells migrate into gonadal ridge
  • Gonads (male/female) identical at this stage (Indifferent)

Gonad development dependent on sex chromosome

• Y present testes
• No Y ovary

DNA with SRY Protein SRY protein binds DNA

Testes determining factor (TDF)

• Transcription factor
• Bends DNA 70–80 degrees

Genital Abnormalities

• Chromosomal
• Hermaphroditism
• Gonadal Dysfunction
• Tract Abnormalities
• External Genitalia
• Gonadal Descent

Chromosomal

• Turner’s Syndrome
• Monosomy XO

99% non-viable embryos Fail to sexually mature at puberty

• Klinefelter’s Syndrome

47, XXY Begin normal male, become infertile Tall, mental dullness, behaviour problems Males 46, XX Develop as male, infertile adults Part of SRY gene located on one X Sex Reversal in Humans

Hermaphroditism True (46,XX) Gonads both ovary and teste tissues Ovotestes or ovary and testes

Male Pseudohermaphrodites (46,XY) Gonads of one sex, external genitalia of opposite Various causes

Female Pseudohermaphrodites (46,XX) Gonads are ovaries, external genitalia ambiguous Hyperplastic adrenals secrete androgens Gonadal Dysfunction Gonads fail to develop properly Gonadal Dysgenesis

Swyer’s syndrome (46,XX)

Mixed Gonadal Dysgenesis (45,X/46,XY)

Primary Hypogonadism Affected females 46,XX Primary Hypogonadism Defective anterior pituitary production of gonadotropin Lack of gonadotropin-releasing hormone

Tract Abnormalities

Many different forms

Uterine

• Associated with other anomalies
• Paramesonephric duct (0.1-0.5% of women)
• several classifications
• Unicornuate, bicornuate uterus

Vagina

• Agenesis, atresia
• See also endocrine disruptors

Ductus Deferens

• Uni- or bilateral absence
• Failure of mesonephric duct to differentiate

External Genitalia

• Multi-factoral
• Chromosomal, single gene, environmental
• Developmental arrest gives ambiguous

Hypospadias

• Common male (1 in 300)
• failure of urogenital folds to fuse
• results in a proximally displaced urethral meatus

Gonadal Descent

Cryptorchidism

• One or both testes fail to descend into scrotum
• 1:30 live male births
• May be associated with other abnormalities

Undescended Ovaries

• reasonably rare, also be associated with other uterine malformations (unicornuate uterus)

Virilization of a Genetic Female with Ovaries

• Fetal androgens
  • congenital adrenal hyperplasia (CAH)
  • adrenal adenoma or hyperplasia
• Maternal androgens
  • ovarian or adrenal tumors
• Latrogenic
  • exogenous androgens or progestagens with androgenic activity

Androgen Insensitivity Syndrome

• XY karyotype and presence of testes
• Externally - develop female secondary sex characteristics
• Internally - women lack Müllerian duct derivatives, have undescended testes