prenatal development

human genetics lecture 11

evolutionary biology

examines how organisms evolve and change, and undergo morphological change throughout generational time

developmental biology

examines how changes in gene expression / gene function modify phenotype, and how patterning arises

evolutionary developmental biology (evo-devo)

examines how developmental mechanisms evolved, looks at the genetic basis of phenotypes, looks at how new structures arise

gametes

spermatozoa or ovum, contain 23 chromosomes, are produced by meiosis

gonads

testes or ovaries, sites of gametogenesis

spermatogenesis

formation of sperm

1. primary spermatocytes undergo meiosis I

2. secondary spermatocytes undergo meiosis II

3. spermatids are modified

4. result: mature spermatocytes (sperm cells)

oogenesis

formation of ovum

1. primary oocytes are stalled during meiosis I (prophase I) during fetal development

2. each menstrual cycle, 1 primary oocyte completes meiosis I, polar body is formed and destroyed

3. secondary oocyte stalls during meiosis II (metaphase II) until fertilization

4. after fertilization by a sperm, secondary oocyte completes meiosis II, polar bodies are formed and destroyed

5. result: 1 mature oocyte (mature ovum, egg), 3 polar bodies

steps of fertilization

1. capacitation of sperm

2. recognition and binding of sperm by egg

3. sperm-egg fusion

4. fusion of sperm and egg pro-nuclei

5. activation of the zygote

capacitation of sperm

modifications made to sperm to allow for fertilization

• increased membrane permeability to facilitate acrosome reaction

• influx of Ca²⁺ and loss of cell surface antigens

• increased motility

recognition and binding of sperm by egg

sperm binds zona pellucida, acrosomal reaction occurs

zona pellucida

layer of glycoproteins that isolates the cytosol of the ovum

sperm-egg fusion

sperm nucleus is transferred into ovum

fusion of sperm and egg pro-nuclei

chromatin decondenses and form new nuclear envelope, resulting in a diploid nucleus

activation of the zygote

cortical reaction to prevent polyspermy, create toughened barrier that will no longer bind sperm

date of implantation

day 8-9 after fertilization

germinal stage

weeks 0-2 after fertilization

embryonic stage

weeks 3-8 after fertilization

fetal stage

week 9 after fertilization to birth

morula

16 cells, formed by blastomeres as a result of cleavage

blastulation

results in the formation of a fluid-filled blastocoel surrounded by blastomeres

blastocysts

formed at day 5 following zygote formation, contain a fluid-filled cavity, trophoblast, and inner cell mass, implants into the uterine wall

trophoblast

layer of cells surrounding the fluid-filled cavity of blastocysts, forms as the zona pellucida disintegrates

inner cell mass (embryoblast)

group of cells in the blastocyst that will develop into the embryo

chorion

two-layered structure formed from trophoblast

• releases human chorionic gonadotropin (hCG) hormone

• grows and forms villi

human chorionic gonadotropin (hCG) hormone

maintains uterine lining and stimulates endometrial cells to produce hormones

villi

exchange nutrients and wastes with maternal blood circulation, eventually form the placenta

gastrulation

involves formation of a recess (blastopore), begins after day 9, marked by further cell differentiation and polarization

cell differentiation

establish cell lineages

cell polarization

establish body axes

ectoderm

outer layer of gastrula

mesoderm

middle layer of gastrula

endoderm

inner layer of gastrula

organogenesis

germ layers begin to develop into discrete organs 4-8 weeks post fertilization

first month of the first trimester

basic tissue layers form, most of the body is divided into paired segments

second month of the first trimester

most major organ systems are formed, becomes a fetus at week 11

third month of the first trimester

sexual development is initiated in the fetus

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 hormonally induced at the end of the third trimester

teratogen

any physical or chemical agent that brings about an increase in congenital malformations, such as radiation, viruses, medications, alcohol

thalidomide

drug prescribed to pregnant women for morning sickness, was later discovered to be teratogenic

fetal alcohol syndrome (FAS)

constellation of birth defects caused by maternal alcohol consumption during pregnancy

control genes

regulate the expression of other genes

levels of sex determination

• chromosomal

• gonadal

• phenotypic

bipotential gonad

for the first 6-8 weeks, the embryo is neither male nor female, both male and female reproductive duct systems develop

gonadal sex differentiation

genes cause gonads to develop as testes or ovaries

wolffian duct

develops into the epididymis, vas deferens, and seminal vesicle under the influence of testosterone and MIS

mullerian duct

develops into the oviduct, uterus, cervix, and vagina in the absence of male hormones

SRY gene

sex-determining region of the Y chromosome, encodes the transcription factor SRY protein or testis determining factor (TDF)

Swyer syndrome

loss of SRY gene region resulting in a lack of male sex characteristics in an individual with XY chromosomes

testosterone

• steroid hormone produced by the testis

• male sex hormone

• converted into DHT

• controls development of wolffian duct

anti-mullerian hormone

• hormone produced by developing testis that causes breakdown of mullerian ducts in the embryo

• mullerian inhibiting substance (MIS)

development of female gonads

requires the absence of the Y chromosome and the presence of two X chromosomes

androgens

hormones secreted by the testis controlling later stages of male sexual differentiation

• testosterone

• dihydrotestosterone (DHT)

• androstenedione

5-alpha-reductase

enzyme that converts testosterone to DHT

androgen insensitivity syndrome (AIS)

mutation in the X-linked androgen receptor gene causes XY individuals to develop into phenotypic females

46, XX intersex

• individual has female chromosomes, ovaries, but external genitals appear male

• usually the result of a female fetus having been exposed to excess male hormones before birth

46, XY intersex

• individual has male chromosomes, but external genitals are incompletely formed, ambiguous, or clearly female

• mostly related to deficiencies in enzymes required for testosterone biosynthesis

sex-influenced and sex-limited inheritance

sex of the individual affects whether the trait is expressed and the degree to which the trait is expressed

pattern baldness

• due to sex-influenced genes → increase androgens / androgen receptors

• acts like a dominant trait in males and recessive trait in females

• highly polygenic

balding scalp

increased concentration of 5-alpha-reductase → increased production of DHT

finasteride

reduces production of DHT by blocking the action of the 5-alpha-reductase, slowing the action of the androgen receptor

sex-limited genes

• loci that produce a phenotype in only one sex

• traits expressed only in females because males die before reproductive age

  • male-lethal X-linked dominant traits

cytoplasmic determinants in human development

gradients of mRNA molecules are organized in human eggs prior to fertilization, creating initial intracellular differentiation

cell signalling

signalling between distant and neighbour cells allows for co-ordination and is essential for division and differentiation

cell specification

cells are defined by the types and amounts of proteins they make

master control genes

transcription factors, proteins that regulate the expression and activity of other proteins

morphogens

transcription factors that control morphological development, determining the animal body plan

activity of morphogens

based on the concentration of the regulatory protein in each particular cell, a series of subsequent signals (cascades) and responses to them dictate the direction and extent of cell growth and development

segmental patterning

results from cascades and the spatial distribution of gene expression / protein products

homeobox

similar stretch of about 180 nucleotides within genes that control body pattern

homeotic (Hox) genes

genes containing a homeobox

evolution of the insect mouth

mouth parts evolved from an ancestral leg, showing serial homology

serial homology

evo-devo has provided powerful empirical evidence that new structures need not evolve de novo, but evolve from pre-existing structures by the modification of pre-existing genetic regulatory circuits

human Hox genes

control the development of our head-to-tail anatomy as embryos

maternal effect genes

expressed in the mother’s ovaries, produce mRNAs placed in different regions of the egg, such as bicoid and nanos mRNA

drosophila bicoid protein

• present in a steep concentration gradient

  • anterior: high levels

  • posterior: low levels

• determines head development

• determines the expression of other body plan genes, such as hunchback and knirps

segmentation

controlled by the interaction of various master genes throughout development