1. Development and Sex Determination
Chapter 7
Development and Sex Determination

2. 7.1 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.

3. Timing of Meiosis and Gamete Formation in Males and Females
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

4. 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

5. Figure 7.5
(1–2) In fertilization, many sperm surround the secondary oocyte and secrete enzymes that dissolve the outer barriers surrounding the oocyte. Only one sperm enters the egg. Penetration stimulates the oocyte to begin meiosis II. (3) The sperm tail degenerates, and its nucleus enlarges and fuses with the oocyte nucleus after meiosis II. (4) After fertilization, a zygote has formed.
Fig. 7-5a, p. 155

6. 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

7. 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

8. 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

9. Trophoblast (surface layer of cells of the blastocyst)
Fertilization
Endometrium
Blastocoel
Implantation
Endometrium
Inner cell mass
Uterine cavity
Inner cell mass
Figure 7.6
Development from fertilization through implantation. A blastocyst forms, and its inner cell mass gives rise to a disc-shaped early embryo. As the blastocyst implants into the uterus, cords of chorionic cells start to form. When implantation is complete, the blastocyst is buried in the endometrium.
1 DAYS 1–2 . The first cleavage furrow extends between the two polar bodies. Later cleavage furrows are angled, so cells become asymmetrically arranged. They are loosely organized with space between them.
2 DAY 3 . After the third cleavage, cells abruptly huddle into a compacted ball, and tight junctions among the outer cells stabilize. Gap junctions formed along the interior cells enhance intercellular communication.
3 DAY 4 . By 96 hours, the embryo is a solid ball of cells called a morula. Cells of the surface layer will function in implantation and give rise to a membrane, the chorion.
4 DAY 5 . A fluid-filled cavity called the blastocoel forms in the morula and the inner cell mass forms. Differentiation occurs in the inner cell mass and gives rise to the embryo proper. This embryonic stage is the blastocyst.
5 DAYS 6–7 . Some of the blastocyst’s surface cells attach themselves to the endometrium and start to burrow into it. Implantation has started. 1 2 3 4 5
Fig. 7-6a, p. 156

10. Chorion
Start of amniotic cavity
Start of embryonic disk
Chorionic cavity
Chorionic villi
Blood-filled spaces
Amniotic cavity
Start of yolk sac
Connective tissue
Start of chorionic cavity
Yolk sac
Figure 7.6
Development from fertilization through implantation. A blastocyst forms, and its inner cell mass gives rise to a disc-shaped early embryo. As the blastocyst implants into the uterus, cords of chorionic cells start to form. When implantation is complete, the blastocyst is buried in the endometrium.
6 DAYS 10–11 . The yolk sac, embryonic disk, and amniotic cavity have started to form from the blastocyst.
7 DAY 12 . Blood-filled spaces form in maternal tissue. The chorionic cavity starts to form.
8 DAY 14 . A connecting stalk has formed between the embryonic disk and the chorion. Chorionic villi, which will be features of a placenta, start to form. 6 7 8
Actual size
Actual size
Actual size
Fig. 7-6b, p. 156

11. 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

12. 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

13. Head growth exceeds growth of other regions
WEEKS 5–6
Head growth exceeds growth of other regions
Retinal pigment
Embryo at 4 to 5 weeks of development.
Future 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

14. Primordial tissues of all internal, external structures now developed
WEEK 8
Final week of embryonic period; embryo looks distinctly human compared to other vertebrate embryos
Figure 7.7
Stages of human development. (a) Human embryo 4 weeks after fertilization. (b) Embryo at 4 to 5 weeks of development. (c) Embryo at week 8, during transition to the fetal stage of development. (d) Fetus at 16 weeks of development.
Upper and lower limbs well formed; fingers and then toes have separated
Primordial tissues of all internal, external structures now developed
Tail has become stubby
(c)
Actual length
Fig. 7-7cd, p. 159

15. 16 centimeters (6.4 inches) 200 grams (7 ounces) Weight:
Placenta
WEEK 16
Length:
16 centimeters (6.4 inches) 200 grams (7 ounces)
Weight:
WEEK 29 Length:
Fetus at 16 weeks of development.
27.5 centimeters (11 inches) 1,300 grams (46 ounces)
Weight:
During fetal period, length measurement extends from crown to heel (for embryos, it is the longest measurable dimension, as from crown to rump).
WEEK 38 (full term)
Weight:
50 centimeters (20 inches) 3,400 grams (7.5 pounds)
Length:
(d)
Fig. 7-7cd, p. 159

16. 7.3 Teratogens Are a Risk to the Developing Fetus
Any physical or chemical agent with the potential to cause birth defects
Radiation, viruses, medications, alcohol

17. 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

18. Defects in physiology; physical Major morphological abnormalities
Tetatogens and their impact on organ formation
Defects in physiology; physical
abnormalities minor
Major morphological abnormalities
Weeks: 1 2 3 4 5 6 7 8 9 16
20–36 38
Cleavage, implantation
Future heart
Future eye
Future ear
Palate forming
Future brain
Limb buds
Teeth
External genitalia
Central nervous system
Heart
Upper limbs
Eyes
Figure 7.8
Teratogens are chemical and physical agents that can produce deformities in the embryo and the fetus. The effects of most teratogens begin after 3 weeks of development. Dark blue represents periods of high sensitivity; light blue shows periods of development with less sensitivity to teratogens.
Lower limbs
Teeth
Palate
External genitalia
Insensitivity to teratogens
Ear
Fig. 7-8, p. 160

19. Mechanisms of Sex Determination
determination vary
from species to
species
XX/XY system
XX/X0
ZW/ZZ
Temp.

20. 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

21. Sexual Development begins in the Seventh week of Gestation
(a) A human embryo at 8 weeks, about the time sex differentiation begins. (b) Two duct systems (Wolffian and Müllerian) are present in the early embryo. They enter different developmental pathways in the presence and absence of a Y chromosome and the SRY gene. (c) Steps in the development of phenotypic sex from an undifferentiated stage to the male or female phenotype. The male pathway of development takes place in response to the presence of a Y chromosome and action of the SRY gene, followed by production of the hormones testosterone and dihydrotestosterone (DHT). Female development takes place in the absence of a Y chromosome and without those hormones.

22. 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

23. 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.

24. 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

25. 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

26. Egg with X sex chromosome
Male
Female
Fertilized by
Fertilized by
Sperm with Y chromosome
Sperm with X chromosome
Chromosomal sex
Embryo with XY sex chromosomes
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
Figure 7.14
The major pathways of sexual differentiation and the stages at which genetic sex, gonadal sex, and phenotypic sex are established.
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
Fig. 7-14, p. 167

27. 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

28. XY Female with Androgen Insensitivity
Figure 7.15
Santhi Soundarajan (green shorts), a phenotypic female who has an XY chromosomal constitution and androgen insensitivity.
Fig. 7-15, p. 168

29. 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

30. 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

31. 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

32. X Chromosomes and Barr Bodies
Figure 7.16
Relationship between X chromosome and Barr bodies. (a) XY males have no inactive X chromosomes and no Barr bodies. (b) XX females have one inactive X chromosome and one Barr body. (c) Females with five X chromosomes have four inactive X chromosomes and four Barr bodies. All X chromosomes except one are inactivated.
Fig. 7-16, p. 169

33. 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

34. Female Mammals are Actually Mosaics for X Chromosome Expression

35. Female Mammals are Mosaics for X Chromosome Expression
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.
Figure 7.18
(a) Photomicrograph of a Barr body (an inactive X chromosome) in a cell from a human female. (b) The mosaic pattern of sweat glands in a woman who is heterozygous for the X-linked recessive disorder anhidrotic ectodermal dysplasia.
(a)
(b)
Fig. 7-18, p. 171

36. Mosaic Expression in Female Mammals
The gene for fur color in cats is on the X chromosome.
Figure 7.17
The differently colored patches of orange and black fur on this calico cat result from X chromosome inactivation (white fur is controlled by a separate gene).
Fig. 7-17, p. 170

37. Inactivation of X Chromosome by XIST RNA
XIST gene codes for RNA that binds to the X chromosome and inactivates it
Figure 7.19
In the female mouse and other female mammals, expression of the XIST gene coats one X chromosome with XIST RNA (red), inactivating it. The active chromosomes in the set are stained blue.
Fig. 7-19, p. 171

38. 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

39. 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.