Beginnings, Growth and Development - Lecture Sexual DifferentiationThis lecture covers embryonic sexual differentiation covering gonad, internal and external genital development. In addition, abnormalities of development are covered. This system continues to develop postnatally (this will be covered in other Lectures).
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Common |
Female |
Male |
Müllerian Duct (paramesonephric) - blue Wolffian Duct (mesonephric) - red |
Use the links below to either view the Lecture slides (1/page) or print (4/page). This lecture should be viewed in conjunction with the BGD Practical Sexual Differentiation
Page Links: Introduction | Lecture Slides | 2005 Lecture Slides | iLecture Broadcast | Quick Lecture Links | Online Resources | Glossary | Slide Text Summary
This is the short summary handout given in the Lecture: Lecture Handout (5 pages 172 Kb)
The links below to PDF versions of lecture slides. Note that movies shown in lecture will not run in these documents and are available from Quick Lecture Links below.
BGD Genital 2007 Lecture - 1 slide/page (52 pages 1.25 Mb)
BGD Genital 2007 Lecture - 3 slides/page (18 pages, 776 Kb)
BGD Genital 2007 Lecture - 4 slides/page (13 pages, 803 Kb)
This is the short summary handout given in the Lecture: Lecture 38 Handout (5 pages 172 Kb)
The links below to PDF versions of lecture slides. Note that movies shown in lecture will not run in these documents and are available from Quick Lecture Links below.
Lecture 38 View 1 slide/page (57 pages 980 Kb)
Lecture 38 Print 4 slides/page (15 pages, 664 Kb)
The external link below is to the previous iLecture (now Lectopia) broadcast of Lecture - Sexual Differentiation from 30 Aug 2005 - 10:00
iLecture 30 Aug 2005 (Note that Lecture starts 2:25 (minutes:seconds) into broadcast).
About UNSW Lectopia : "The Lectopia system enables automated digital recording of lectures that can then be accessed via streaming media over the web and can also include PowerPoint presentations. Other files such as PDF's and Word Documents can also be uploaded." (both Quicktime and Windows Media are supported)
Urogenital Development notes look at both Kidney and Genital development.
Genital Development notes look at Genital development including Abnormalities | Female | Uterus | Male | Y Chromosome | X Chromosome
Endocrine Development look at Endocrine Gonad and Hypothalamus / Pituitary notes.
Oogenesis mainly covers mature ovary.
Spermatogenesis mainly covers mature ovary.
These are movies shown in the Lecure slides. Note that movies require quicktime to be installed on your computer.
Urogenital Movies link takes you to a page with movies shown in the Lecture.
UNSW Embryology
BGD Practical Sexual Differentiation
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001.The Gonad
Molecular Biology of the Cell (4th ed.) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Influence of Sry on gonad development.
Embryo Images by Drs. Kathleen K. Sulik and Peter R. Bream Jr. Linked notes and images sections on Urogenital Development
Anatomy of the Human Body Commercial linked notes/images sections from Gray’s Anatomy of the Human Body 3. The Urogenital Apparatus
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z
Note that not all slide text shown and text out of context may not make sense to you in this bullet list form.
Gonad
Internal Genitalia
# Reproductive Tract
External Genitalia
# Development
# Function
# Abnormalities
Notes
# Fertilization
# Week 1
# Kidney
# Endocrine
UNSW Embryology
# Gonad Development
## http://embryology.med.unsw.edu.au/Notes/urogen.htm
NIH Bookshelf
# Developmental Biology (Gilbert)
- Chapter 17
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=dbio.chapter.4101
# Endocrinology (Nussey and Whitehead)
- The Gonad
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=endocrin.chapter.972
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
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 Timecourse
# Begins in embryo
# Finishes in puberty
X Chromosome
# 1400+ genes
# 150 million base pairs
# 95% determined
Chromosome Y
# 200+ genes
# 50 million base pairs
# 50% determined
Genes such as Wnt-4 and DAX-1
necessary for initiation of female pathway ovary development
female not considered a default process
Sry gene on Y chromosome
# responsible for testis-determining function
# TDF
# expressed in a subset of somatic cells in developing gonad
# induces cells to differentiate into Sertoli cells
Sertoli cells
# produce signals that promote development of male characteristics
# suppress development of female characteristics
# induce primordial germ cells to commit to sperm development
SRY protein binds DNA
# Testes determining factor (TDF)
# Transcription factor
Bends DNA 70–80 degrees
# Black
- SRY protein HMG box
# Red coil - DNA double helix (Image after Haqq et al. 1994 and Werner et al. 1995)
Early germ line separation from somatic cells
## germ cells do not arise within gonad
Precursors primordial germ cells (PGCs)
## arise elsewhere and migrate into developing gonads
Gametogenesis
## forming PGCs and getting them into genital ridge as gonad forms
## formation of germ plasm and determination of PGCs
## migration of PGCs into developing gonads
## process of meiosis and modifications of meiosis for forming sperm and eggs
## differentiation of sperm and egg
## hormonal control of gamete maturation and ovulation
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 testes
# No Y ovary
All embryos form paired
# Nephric duct
# 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)
- Causes regression of paramesonephric duct
# Testosterone
- Retains mesonephric duct
Female - opposite
After colonization of gonad
female germ cells enter prophase of first meiotic division as a mid-gestational hallmark of gender
Perinatally oocytes interact with granulosa cells to form primordial follicles
# cyclic periodicity enter a 3 week growth phase that culminates in meiotic maturation and ovulation
# (study in mouse)
Inactive until puberty
Seminiferous tubules
## Initially solid (cellular)
## Hollow and active at Puberty
Cyclic sperm production along length of tubule
# Hormonal production of differentiated gonads
## required for differentiation of internal and external genitalia during fetal life
## development of secondary sex characteristics at puberty
# Antimullerian hormone (AMH) secreted by Sertoli cells
# Testosterone secreted by Leydig cells
# External male genitalia
## requires transformation of testosterone to dihydrotestosterone
## 5alpha reductase type 2 expressed in genital skin and urogenital sinus
# effects of androgens occur in presence of functional androgen receptor protein
## Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity
All embryos initially same (indifferent)
Testosterone
# Differentiates male
Fetal Development
Chromosomal
Hermaphroditism
Gonadal Dysfunction
Tract Abnormalities
External Genitalia
Gonadal Descent
Cryptorchadism
# One or both testes fail to descend into scrotum
# 1:30 live male births
# May be associated with other abnormalities
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
- Portion of SRY gene located on one X
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
# 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
# Many different forms
Uterine
- Associated with other anomolies
Vagina
# Agenesis, atresia
- See endocrine lecture DES
Ductus Deferens
# Uni- or bilateral absence
- Failure of mesonephric duct to differentiate
Multi-factoral
# Chromosomal, single gene, environmental
# Developmental arrest gives ambiguous
XY karyotype and presence of testes
Externally
# develop female secondary sex characteristics
Internally
# women lack Müllerian duct derivatives
# have undescended testes
not known significance of brain sex differences
transient sex differences in gene expression in developing brains may cause permanent differences in brain structure
may prevent as well, by compensating for potentially differentiating effects of sex differences in gonadal hormone levels and sex chromosomal gene expression
Brains of males and females differ
## in regions specialized for reproduction
## 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 the brain have been attributed to the 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
Factors that increase gonadotrophin secretion and stimulate gonadal maturation
Bars show proportional rise in testosterone and estradiol secretions in males and females respectively
Activation of positive feedback mechanism of estradiol in females also occurs during puberty
gonads, internal genital ducts, and external genital structures develop from bipotential embryologic tissues
Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation
Karyotype (46, XY or 46, XX)
# of embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary respectively (gonadal differentiation)
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This is a new Lecture developed for BGD. It contains many new concepts and terms you may not have heard before. This should become clearer once you nave done some of the associated Laboratories.
Some lecture slides within the Lecture Slide PDFs were not shown during the lecture and are provided to aid your understanding.
These notes and linked materials have been prepared for Educational purposes only.
Please email Dr Mark Hill if you wish to make a comment about this current project.