Development and Sex Determination Chapter 7 Development and Sex Determination

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

Mechanisms of Sex Determination 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 (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.

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

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

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 Figure 7.15 Santhi Soundarajan (green shorts), a phenotypic female who has an XY chromosomal constitution and 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 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

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

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

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

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

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.