Michael Cummings

David Reisman • University of South Carolina

Development and Sex Determination

Chapter 7

7.1 The Human Reproductive System

The human reproductive system• We will not cover most of this information in this

course because it is focused on anatomy rather than human genetics.

Timing of Meiosis and Gamete Formation in Males and Females Males• Spermatogenesis begins during puberty• Millions of sperm are always in production• Spermatogenesis takes about 48 days• Each cell that undergoes meiosis produces 4 sperm

Females• Primary oocytes produced during embryonic

development remain in meiosis I until ovulation• Ovulation begins during puberty• Meiotic division produces 1 large oocyte and 2-3 polar

bodies

The Largest Cell

The human oocyte is the largest cell produced in the body. It is large enough to be seen with the naked eye

Fig. 7-5a, p. 155

7.2 From Fertilization to Birth

Cell divisions in the zygote form an early embryonic stage called the blastocyst

Blastocyst • The developmental stage at which the embryo

implants into the uterine wall • Stem cells are derived from a blastocyst

Inner cell mass • A cluster of cells in the blastocyst that gives rise to the

fetus

Implantation

Implantation The embryo implants in the uterine wall, and

membranes develop to support the embryo

Trophoblast • Outer layer of cells in the blastocyst that gives rise to

the membranes surrounding the embryo

Embryonic Membranes and Placenta

Chorion • formed from trophoblast• Releases human chorionic gonadotropin (hCG)

hormone which maintains uterine lining and stimulates endometrial cells to produce hormones—hCG is what pregnancy tests detect

• Grows to eventually form the placenta

Fig. 7-6a, p. 156

Fertilization

Trophoblast (surface layer of cells of the

blastocyst)

Endometrium

ImplantationEndometrium

Blastocoel

Inner cell mass

Uterine cavity

Inner cell mass

21 3 54

Fig. 7-6b, p. 156

Start of amniotic cavity

Start of embryonic disk Blood-filled spaces Chorionic villi

Chorionic cavity

Chorion

Amniotic cavity

Connective tissue

Start of yolk sac

Start of chorionic cavity

Yolk sac

Actual size

Actual size

Actual size

6 87

Development is Divided into Three Trimesters

First trimester• First month: basic tissue layers form; most of the body

is divided into paired segments• Second month: most major organ systems are formed• Third month: embryo becomes a fetus; sexual

development is initiated

Development is Divided into Three Trimesters

Second trimester• Increase in size and organ-system development• Bony parts of skeleton form• Heartbeat is heard with a stethoscope• Fetal movements begin

Third trimester• Rapid growth• Circulatory and respiratory systems mature• Birth is a hormonally induced process at the end of the

3rd trimester

WEEKS 5–6

Head growth exceeds growth of other regions

Retinal pigmentFuture external ear

Upper-limb differentiation (hand plates develop, then digital rays of future fingers; wrist, elbow start forming)

Umbilical-cord formation between weeks 4 and 8 (amnion expands, forms tube that encloses the connecting stalk and a duct for blood vessels)Foot plate

(b) Actual length Fig. 7-7ab, p. 158

WEEK 8Final week of embryonic period; embryo looks distinctly human compared to other vertebrate embryos

Upper and lower limbs well formed; fingers and then toes have separated

Primordial tissues of all internal, external structures now developedTail has become stubby

(c) Actual length Fig. 7-7cd, p. 159

Fig. 7-7cd, p. 159

Placenta

WEEK 16 Length: 16 centimeters (6.4 inches)

200 grams (7 ounces)Weight:

WEEK 29 Length: 27.5 centimeters (11 inches)

1,300 grams (46 ounces)Weight:

WEEK 38 (full term)

Length:50 centimeters (20 inches) 3,400 grams (7.5 pounds)

Weight:

During fetal period, length measurement extends from crown to heel (for embryos, it is the longest measurable dimension, as from crown to rump).(d)

7.3 Teratogens Are a Risk to the Developing Fetus

Teratogen • Any physical or chemical agent with the potential to

cause birth defects• Radiation, viruses, medications, alcohol

Alcohol is a Teratogen

Fetal alcohol syndrome (FAS) • A range of birth defects caused by maternal alcohol

consumption during pregnancy

Alcohol is the most common teratogenic problem and leading cause of preventable birth defects• There is no “safe” amount of alcohol consumption

during pregnancy

Fig. 7-8, p. 160

Defects in physiology; physical

abnormalities minorMajor morphological

abnormalities

Weeks: 1 2 3 4 5 6 7 8 9 16 20–36 38Cleavage, implantation

Future heart Future

eyeFuture ear

Palate forming

Limb buds Teeth External genitalia

Central nervous system

HeartUpper limbs

Eyes

Lower limbs

Teeth

Palate

External genitaliaInsensitivity to teratogens Ear

Future brain

Tetatogens and their impact on organ formation

Mechanisms of Sex Determination

Mechanisms of sex determination vary from species to species

XX/XY system

XX/X0

ZW/ZZ

Temp.

Human Sex Ratios

Sex ratio • The proportion of males to females changes

throughout the life cycle • The ratio at conception is slightly higher for males.(**prenatal deaths most likely due to lethal X-linked recessive alleles)

• The ratio at birth is about 105 males/100 females• The ratio of females to males increases as a

population ages

Sexual Development begins in the Seventh week of Gestation

7.5 Defining Sex in Stages: Chromosomes, Gonads, and Hormones

Sex of an individual is defined at three levels• Chromosomal sex (established at fertilization)• Gonadal sex (begins around week 7 or 8 of

embryogenesis)• Phenotypic sex

Gonadal and phenotypic sex depend on the interaction of genes and environmental factors, especially hormones

Gonadal Sex Differentiation

For the fist 7 or 8 weeks, the embryo is neither male nor female• Both male and female reproductive duct systems

begin to develop

Genes cause gonads to develop as testes or ovaries, establishing gonadal sex• Alternative pathways produce an intermediate sex for

1 out of every 2000 births.

Y Chromosome and Testis Development

SRY gene• Sex-determining region of the Y chromosome• Plays a major role in causing the undifferentiated

gonad to develop into a testis• Testis development causes secretion of testosterone

Müllerian inhibiting hormone (MIH) • Hormone produced by developing testis that causes

breakdown of Müllerian (female) ducts in the embryo

Female Development

Requires the absence of the Y chromosome and the presence of two X chromosomes for the embryonic gonad to develop as an ovary

In the absence of testosterone, the Wolffian duct system degenerates

In the absence of MIH, the Müllerian duct system forms female reproductive system

Fig. 7-14, p. 167

Egg with X sex chromosomeMale Female

Fertilized by Fertilized bySperm with Y chromosome

Sperm with X chromosome

Embryo with XY sex chromosomes

Chromosomal sex Embryo with XX sex

chromosomes

Sex-determining region of the Y chromosome (SRY) brings about development

of undifferentiated gonads into testes.

No Y chromosome, so no SRY. With no

masculinizing influence, undifferentiated gonads

develop into ovaries.

Gonadal sex

Testes secrete masculinizing hormones, including testosterone, a

potent androgen.No androgens secreted

In presence of testicular hormones, undifferentiated

reproductive tract and external genitalia develop

along male lines.

With no masculinizing hormones, undifferentiated

reproductive tract and external genitalia develop

along female lines.

Phenotypic sex

Androgen Insensitivity

Androgen insensitivity (CAIS)

A mutation in the X-linked androgen receptor gene (AR) causes XY males to become phenotypic females• Testosterone is produced, but not testosterone

receptors; cells develop as females

XY Female with Androgen Insensitivity

Fig. 7-15, p. 168

Exploring Genetics: Joan of Arc or John of Arc?

Joan of Arc fought with the French at the Battle of Orleans, and was burned as a heretic by her enemies, the English, in 1431

From an examination of trial evidence and records of her physical examinations, R.B. Greenblatt proposed that Joan had phenotypic characteristics of androgen insensitivity

Mutations can cause Sex Phenotypes to Change at Puberty

Pseudohermaphroditism • Mutations in several different genes cause XY

individuals to develop the phenotype of females• Affected individuals have structures that appear

female at birth• At puberty, testosterone burst causes a change into

the male phenotype

7.7 Equalizing the Expression of X Chromosomes in Males and Females Lyon hypothesis (proposed by Mary Lyon) • How do females avoid getting a double dose of protein

from X-linked genes?• Random inactivation of one X chromosome in females

equalizes the activity of X-linked genes

Barr body • A densely staining mass in the somatic nuclei of

mammalian females • An inactivated X chromosome, tightly coiled

X Chromosomes and Barr Bodies

Fig. 7-16, p. 169

Female Mammals are Mosaics for X Chromosome Expression

In females, some cells express the mother’s X chromosome and some cells express the father’s X chromosome• Inactivated chromosome can come from either mother

or father• Inactivation occurs early in development• Inactivation is permanent; all descendants of a

particular cell have the same X inactivated

Female Mammals are Actually Mosaics for X Chromosome Expression

Fig. 7-18, p. 171

Unaffected skin (X chromosome with recessive allele was condensed; its allele is inactivated. The dominant allele on other X chromosome is being expressed in this tissue.)

Affected skin with no normal sweat glands (yellow). In this tissue, the X chromosome with dominant allele has been condensed. The recessive allele on the other X chromosome is being transcribed.

(a)(b)

Female Mammals are Mosaics for X Chromosome Expression

Mosaic Expression in Female Mammals

Fig. 7-17, p. 170

The gene for fur color in cats is on the X chromosome.

Inactivation of X Chromosome by XIST RNA

Fig. 7-19, p. 171

XIST gene codes for RNA that binds to the X chromosome and inactivates it

7.8 Sex-Related Phenotypic Effects

Sex-limited trait - affects a structure or function of the body that is present in only males or females • Women do not get prostate cancer, women do not

grow beards but pass on the gene for beard growth on to their sons

Sex-influenced trait - an allele is dominant in one sex and recessive in the other • Baldness—the allele is dominant in males and

recessive in females

Imprinting

Imprinting • difference in expression of a gene depending upon

whether it was inherited from mother or father

• More discussion to follow on this topic in Chapter 11.