Amniotes - Mammals

Dr. Frances Oldham Kelsey

Canadian scientist who worked for US FDA

• refused to approve thalidomide for use in the US 

Alecithal Egg

An egg with little yolk

• Human egg is about 100um in diameter

Oviduct

Where fertilization occurs

• maternal meiosis is completed at fertilization

• embryo develops and travels before uterus implantation

  • around 72hrs in humans

Oddities of Mammalian Cleavage

Some things set mammalian cleavage aside from other taxa

• slow cleavage 

• rotational cleavage 

• asynchronous cleavage 

• early genome activation 

• compaction

Compaction

The process by which cell constrict themselves to occupy a smaller amount of space and become more closely associated

• occurs at 8 cell stage due to increased cadherin expression 

Blastocyst

Formation directed through the inside-out theory and consists of two main parts

• trophoblast 

• inner cell mass 

Trophoblast

Outer cells lining fluid filled space 

• Is the chorion/placenta precursor

Inner Cell Mass

Is a pluripotent mass of about 16 cells that stimulates trophoblast mitosis

• will form, embryo, yolk sac, and amnion

Inside Out Theory

Idea that the important development happens inside

Implantation

Blastocyst will hatch from the zona pellucida and stimulate the implantation process

• will implant in uterine wall around 7-12 days after fert in humans 

Ectopic Pregnancies

Occurs when the embryo hatches too early and implants in an incorrect location

Gastrulation and Neurolation

Process is similar to that of birds

• Heralds the presence of visible structures

• Hensen’s induces cell fates

Embryo Folding and Amnion Formation

The flat embryo elongates and folds

• yolk sac is reduced

• amnion grows to surrounds the embryo

Placenta

Tissue from both embryo and mother

• embryo’s blood vessels branch into uterus to form chorionic villi

• provides increased SA to contact with maternal blood for nutrition

• bloods do not mix

• functional at 12 weeks

Placenta and Viability

In mice there are about 5000 genes associated with embryo mortality

• 2/3 associated with placenta

• 1/3 associated with brain/heart

Extraembryonic Membranes

Visible after 40 days 

• chorion, amnion, yolk sac, umbilical chord

Extra Embryonic: Chorion

Rich in blood vessels for nutrition

Extra Embryonic: Amnion

Shock absorber

Extra Embryonic: Yolk Sac

Source of some extraembryonic membrane cells, early blood cells, and germ cell refuge

Extra Embryonic: Umbilical Cord

Stalk of cells connecting the embryo to the trophoblast

Early Embryos

• Engage in a form of regulative development where lost/damaged cells may be replaced during the blastocyst stage 

• All cells of inner cell mass are totipotent stem cells 

• Cell fate is determined by interactions among SC descendants in the ICM 

Monozygotic Twins

• Splitting at two cell stage forms separate placentas and associated structures

• Splitting in early blastocyst forms shared placenta/chorion but separate amnions

• Later splitting forms two embryos from same inner cell mass which share all extraembryonic structures

Dizygotic Twins

Separate fertilizations

Conjoined Twins

Occurs when ICM divides between 9 and 13 days after fert

• more commonly female 

• caused by a variety of factors 

• 1/200k live births but 1/40k births

Embryo Fusion

Multiple embryos may fuse in to one during compaction if they are closely associated

• happens most in animals with multiple spawn

Chimeras

Three main groups of individual who have multiple genomes

• microchimeras develop by feto-maternal cell movement across placenta

• fusion chimera formed by zygotic fusion

• twin chimeras caused by cell transfer between dizygotic twins sharing a placenta

Errors

1/4 to 2/3 of human conceptions do not develop to term

• most issues occur in the 1st month due to implantation fails or spontaneous abortion

After birth 5% have some recognizable non-deleterious malformation

Teratogenesis

Developmental disruptions caused by exogenous agents

• most effective between3-8 weeks in human development

Sensitive Periods

Certain times during development where different parts of the organism are more or less susceptible to teratogenic effects 

Retinoic Acid

Localized morphogen in low amounts that allows proper formation of the anterior-posterior axis as well as limb and jaw dev

• high concentrations causes congenital abnormalities dependent on the level an timing of exposure

Thalidomide

Anti-nausea drug marketed to cure morning sickness in the 1950s

• currently used to treat leprosy

• was a teratogen that caused abnormal limb development by inhibiting mesoderm mitosis and angiogenesis