2009 BGD-B Lecture Sexual Differentiation

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Introduction

Historic Image of female urogenital sinus development

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 yet complete. The genital system is anatomically and developmentally associated with the urinary system and is often described as the urogenital system.

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)

Objectives

Understand the role of the Y chromosome in sex determination.
Understand the differences in male/female duct develpoment (mesonephric/paramesonephric).
Compare the development of the cloaca in the male and female.
Understand the developmental abnormalities in male and female development.

Lecture Overview

Gonad
Internal Genitalia
Reproductive Tract
External Genitalia
Development
Function
Abnormalities

Background Reading

UNSW Embryology

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 pp303-346
Before We Are Born (5th ed.) Moore & Persaud Chapter 14 pp289-326
Essentials of Human Embryology, Larson Chapter 10 pp173-205
Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 pp134-152

Genital System Development

3 stages

Differentiation of gonad (sex determination)
Differentiation of internal genital organs
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

Gonad

gastrulating mammalian embryo
cells signaled by neighbours
form primordial germ cells (pgc)
migrate into genital ridges which develop into gonads

Primordial germ cells develop into

eggs, if gonad is becoming an ovary
sperm, if gonad is becoming a testis

Gonad will develop into an ovary unless its somatic cells contain a Y chromosome

Human Molecular Genetics - Development of the germ line

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

Internal Genital Tract

Female - paramesonephric - uterus
Male - mesonephric - ductus deferens

All embryos form paired

Mesonephric duct - see kidney development
Paramesonephric duct - Humans 7th week Invagination of coelomic epithelium Cord grows and terminates on urogenital sinus

Male Gonad (testes) secretes
- Mullerian duct inhibitory factor (MDIF) which causes regression of paramesonephric duct
- Testosterone which retains mesonephric duct

Caspar Friedrich Wolff (1733 – 1794) in 1759 was the first to describe the "Wolffian duct" also called the mesonephric duct.

Johannes Peter Muller (1801 – 1858) in 1830 was the first to describe the "Mullerian duct" also called the paramesonephric duct.

External Genital Organs

All embryos initially same (indifferent)
Testosterone - differentiates male
- Male Hormone dependent anatomy

Endocrinology - External Genital Development

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 (see Sex Reversal in Humans)

Hermaphroditism

True Hermaphroditism (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

Puberty

Hormone Axis LH & FSH
Difference in timing
increased gonadotrophin secretion and stimulate gonadal maturation
rise in testosterone and estradiol secretions in males and females respectively
positive feedback of estradiol in females also occurs during puberty
secondary sexual characteristics

Tanner Stages

External Genitalia
Mammary

Endocrinology - Tanner Stages

Mammary Glands

sex hormone secretion of ovarian hormones estrogen and progesterone
lead to reciprocal signaling between the epithelium and stroma
branching and elongation through the stroma forming extensive network of ducts
full development approx 20 years
mainly fat and connective tissue deposition
growth also influenced by other hormones
prolactin, corticoids, growth hormone

Integumentary Development - Mammary Glands

Sex and Brain Differentiation

Brains of males and females differ
- regions specialized for reproduction
- Also in other regions (controlling cognition, etc) where sex differences are not necessarily expected
Differentially susceptible to neurological and psychiatric disease
2 sources of sexually dimorphic information
- complement of sex chromosome genes
- mix of gonadal hormones
sex differences in brain attributed to differential action of gonadal hormones
evidence for sex chromosome effects on both neural and non-neural systems
XX and XY cells differentiate even before they are influenced by gonadal hormones
- even if exposed to similar levels of gonadal steroids

References

Search Online Textbooks sexual differentiation | puberty

Search Entrez sexual differentiation | puberty

Links

Anatomy of the Human Body, Henry Gray (1918) 3. The Urogenital Apparatus

Cite this page: Hill, M.A. (2024, April 24) Embryology 2009 BGD-B Lecture Sexual Differentiation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2009_BGD-B_Lecture_Sexual_Differentiation

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