Repro physiology 7 – Embryogenesis, maternal recognition of pregnancy and placentation

What is occurring Post-fertilization,

the zygote must divide and develop into an embryo

The zygote undergoes a series of divisions (cleavage), before the

cells differentiate to form organs

Maternal recognition of pregnancy is essential for

embryo implantation

Placenta must be successfully formed for development of

fetus

The organs develop further during the

fetal period, and the fetus becomes a neonate (new-born individual) at parturition

Embryonic period is

• Time from fertilization to the earliest stages of organ development

• Days 0-30 in dog, cat, sheep and goat

• Days 0-60 in horse and cattle

Fetal period

• Time between the embryonic period and parturition (birth),

• Organs grow and begin to function

• Days 30-64 in cats and dogs

• Days 30-147 in sheep and goat

• Days 60-285 in cattle

• Days 60-337 in horse

Holoblastic

• Small, even yolk

• Equal cleavage

• Equal daughter cells

• All blastomeres closed

• Ovum can be small (because of placenta!)

• e.g., human, most mammals

Meroblastic

• Large yolk

• Unequal cleavage

• Unequal daughter cells

• Cleavages leave nucleus open to rest of cell

• Ovum large

• e.g., bird, reptiles

Morula compacts and cells differentiate to form:

• Central mass of cells called the inner cell mass → embryo body

• Layer surrounding the cavity → trophectoderm → placenta and fetal membranes

• Differentiation is due to differential gene expression

Trophectoderm cells get flattened and secrete fluid to form

• cavity (blastocoele)

• Embryo now called blastocyst

Zona pellucida disintegrates and

blastocyst implants in uterus

It is the blastula stage that is collected from

donor animals, for embryo transfer.

Fertilization occurs in the

uterine tube, and the morula stage embryo enters the uterus on day 4.

The blastocyst is formed by day

day 6 and hatches from the zona pellucida on days 8–9.

The blastocyst develops from a spherical to a

tubular form by day 11 and then elongates to a filamentous conceptus between days 12 and 16.

The elongation of the blastocyst marks the beginning of

implantation, which involves apposition and transient attachment (days 12–15) and firm adhesion by day 16.

Equine blastocyst

• Between days 9-16

• Grows very little, remains spherical

• Migrates around uterus several times

Equine blastocyst is driven by

Probably driven by PGE2

Bovine, ovine, porcine blastocyst

• Elongates rapidly

• To deliver antiluteolytic signal to the entire endometrium

Maternal recognition of pregnancy must occur prior to

luteolysis

The conceptus (embryo) must provide a timely

biochemical signal, else the pregnancy will terminate

Maternal recognition of pregnancy: Human:

hCG (prevents luteolysis)

Maternal recognition of pregnancy: Cow:

IFN-τ (prevents PGF2α)

Maternal recognition of pregnancy: Pig:

E2 (redirects PGF2α)

Maternal recognition of pregnancy: Horse:

(redirects PGF2α to lumen of uterus)

Interferon tau (IFN-τ) secreted by

trophoblast from blastocyst

stage

IFN-τ: does what

• Does not ↑ luteal function

• ↓endometrial oxytocin receptor (OTR) synthesis

• Prevents oxytocin-induced PGF2 production

• Promotes protein secretion from uterine glands (pre-implantation)

• Role in endometrial differentiation and implantation

Maternal recognition of pregnancy – mare: Equine chorionic gonadotrophin (eCG):

• Role in pregnancy not completely understood

• Does not prevent PGF2α secretion

• Luteogenetic and luteotrophic (supports luteal function and leads to formation of supplementary CL)

• Day 120 gestation = ↓ eCG and luteolysis (pregnancy supported to D330 by placental P4)

• Acts as FSH & LH: used for stimulation follicular growth in various species

Human chorionic gonadotrophin (hCG)

• Acts like LH

• Can be used to induce ovulation

hCG functions:

• Luteotrophic(i.e., ↑ progesterone secretion)

• ↑ angiogenesis/bloody supply in uterus

• Prevents luteolysis (mechanisms poorly known)

• Stimulates ↑ PGE2 (cause of morning sickness and may ↓ PGF2α?)

• Regulate metabolism/nutrient partitioning?

Maternal recognition of pregnancy – dogs and cats

• Lack of information on maternal recognition

• Not required: why?

• Pseudopregnancy in dogs

• Normal luteal phase ~ half gestation - switch from luteal to placental P4

production during mid-gestation in cats

Gastrulation:

formation of the three germ layers - ectoderm,

mesoderm and endoderm

Neurulation:

formation of neural tube, a precursor to brain and

spinal cord

Segmentation:

formation of somites, precursor to vertebrae

Organogenesis:

formation of different organs

Types of placenta: Diffuse: in what animals

horse and pig

Types of placenta: Cotyledonary:: in what animals

ruminants

Types of placenta: Zonary::: in what animals

dogs and cats

Based on placental barriers Epitheliochorial:

ruminants, pig, horse

• 3 maternal layers; 3 fetal layers

Based on placental barriers Endotheliochorial: dog and cat

• 1 maternal layer (endothelium); 3 fetal layers

Based on placental barriersHaemochorial:

humans and rodents

• No maternal tissue; 3 fetal layers

Progesterone (P4) concentrations are high or low

high

Oestrogen (E2) concentrations are high or low

low

Progesterone (P4) and Progesterone (P4) prevent what

This prevents uterine contractions

Where do these hormones come from?

• Corpus luteum (CL)

• Placenta

Progestins which animals sufficient progestin is

secreted by the placenta

• (women, horses, sheep, cats),

Progestins which animals luteal P4 is necessary

throughout gestation

• (cattle, pigs, goats, dogs),

Oestrogens in women is called?

oestriol

Oestrogens in ruminants is called?

oestradiol

Oestrogens in mare is called?

unique compounds

Who has Chorionic gonadotrophin (CG)

• In primates and equids

hCG: responsible for

• Signal for maternal recognition of pregnancy

• Cause of morning sickness

• Binds to LH receptor on CL – prevents luteolysis

• Increases P4 secretion

• Aids placental formation

• Increases blood supply to the uterus

eCG also known as Pregnant Mare Serum Gonadotropin (PMSG)

• eCG has activity like FSH and LH

• Used to stimulate ovulation and superovulation in sheep

• Response is dose dependent

Placental lactogen (PL)

• Like prolactin and GH

• In primates, ruminants and rodents

• Inhibit gonadotrophins and stimulates mammogenesis

Relaxin

• Produced by CL and placenta (fetalmembranes)

• Aids P4

• Relaxes pelvic ligaments at end of gestation

• Allows passage of foetus

Most organs formed by

6 weeks

Heart by

3 weeks

Exponential Growth

• More than 50% during last 2 months

Foetus derives nutrients from dam

• Glucose (50%), amino acids (25%) and short chain fatty

acids (25%)

Factors affecting foetal growth

• Foetal genotype

• Maternal genotype

• Dam age

• Dam nutrition

• Litter size

• Ambient temperature

Factors affecting foetal growth: foetal genotype

• Foetus inherits genes from both sire and dam

• Calves from large breeds grow rapidly in uterus

• e.g., HF claves bigger at full term compared to Jersey

• Males grow faster compared to females

Factors affecting foetal growth: maternal genotype

• Dams of large breeds produce bigger claves

• e.g., Angus-Friesian claves bigger in Friesian dams

compared to Angus-Friesian claves in Angus cows

• Large dams have greater ability to supply nutrients

• Maternal genotype more influence than paternal genotype

Factors affecting foetal growth: dam age

• Young dams produce lighter offspring

• Not yet reached mature weight

• Are still growing

• Need to be adequately fed

• Mature dams produce bigger progeny

Factors affecting foetal growth: dam nutrition

• Dams exhibit mild buffering effect to over and under nutrition

• Slight changes usually have no effect on foetal growth

• Poor condition of dam can be detrimental

• Low birth weight

• Neonatal mortality

• Improper mammogenesis and low milk production

• Over nutrition can also have negative effects

• Very large progeny leading to dystocia

Factors affecting foetal growth: litter size

• Larger than normal litter size has negative effect of birth weight

• Gestation length can decrease in case of large litter size in cattle

Factors affecting foetal growth: ambient temperature

• High ambient temperature reduces birth weight

• Decrease in feed intake

• Reduced placental development

Maternal stabilising effect on foetal growth

• Dam has an amazing control on the size of foetus

• Makes sure it is not too small or not too large

• Progeny from a very large breed of bull (e.g., a South Devon

of 1100 kg mature weight) mated to a small breed of cow

(e.g., a Dexter of 450 kg mature weight) will only be 2 kg

heavier

• A poorly fed cow that loses 50 kg body weight would produce

calf that is about only 1 kg lighter

• A vital adaptation for better survival of offspring

Fetal growth restriction

• Alterations in fetal nutrition and endocrine status may

result in developmental adaptations that permanently

change the following in the offspring

• Structure

• Physiology

• Metabolism

• Postnatal growth

Due to epigenetic effect i.e., alterations of gene

expression through

DNA methylation and histone

modifications of the fetal genome