Hormones of pregnancy

Pregnancy

• Preparation of uterus– Steroid hormones

• Fertilization– Coitus– Gamete transfer– Capacitation of sperms– Fusion of gamates

• Embryonic development– Preimplantation– Implantation

• Placentation• Differentiation of cells• Organogenesis

• Must alter cyclic changes in the ovarian steroid hormones– Progesterone

• High • Must maintain the CL

– Most species– Some can maintain pregnancy without CL after

certain stage (placental progesterone)

Luteolysis• Destruction of the CL

– Reinitiation of reproductive cycle– Two types

• Active• Passive

• Active luteolysis– Production of luteolytic agent (PGF2)

• Uterus

• Passive luteolysis– Loss of luteotropic agents

Active luteolysis

• Communication from uterus to ovary– Approximately 4 days

before estrus, the uterus begins to produce PGF2,

– PGF2diffuses into the bloodstream feeding the ovary bearing the CL (ovarian artery).

PGF2

Uterinevein

Ovarian artery

Large black arrows indicatedirection of PGF2 flow

• From uterus to ovary – Interaction between

PGF2 and its receptor

• Large luteal cells

• Decreased production of progesterone

• Death of the luteal cells– Elevated intracellular

Ca level– Constriction of blood

vessels

• Release of oxytocin.

PGF2

Progesterone

Oxytocin

PGF2

• From ovary to uterus (and back to the ovary)– Oxytocin

• Reaches the uterus and stimulates production of more PGF2

– Increasing amount of estradiol from the large follicle

• Increased production of PGF2 by uterus through increased sensitivity to oxytocin

PGF2

Progesterone

Oxytocin

PGF2

• From ovary to uterus (and back to the ovary)– Positive feedback loop

• Uterine production of PGF2

• Production of oxytocin by the CL

– Ultimately leads to corpus luteum regression

• Reinitiation of reproductive cycle

PGF2

Progesterone

Oxytocin

PGF2

Local regulation of reproductive cycle

• Progesterone production by CL – Begins to decline. – Initiated by increased

production of PGF2

– Increased production of PGF2

• Ablated when pregnancy has been initiated, resulting in continued Progesterone production by the CL and pregnancy maintenance

PGF2

Progesterone

Pregnancy

Maternal recognition of pregnancy

• Two types– Anti-luteolytic

• Diversion of PGF2 secretion

• Inhibition of PGF2 secretion

– Luteotropic• Maintenance of the CL by providing necessary

hormone– Gonadotropin

Early embryonic development

• Zygote – Begins to divide as it moves through the oviduct towards the

uterus– Numbers of cells increase after each division

• The size of the embryo does not (cell size decreases by approximately 20 % after each division)

AmpullaIsthmus

Ampullary-isthmic Junction

Uterotubal Junction

Early embryonic development

• Cells of the embryo remain within the zona pellucida as they divide– The size of the nucleus increases– All chromosomes remain intact– In cows, the embryo divides three to four times (approximately one

division a day) while in the oviduct• Usually at the 16-cell or morula stage when it reaches the uterus

2-cell embryo 8-cell embryos

Early embryonic development

• Morula stage– All the cells of the embryo

are in a tightly packed clump – Cells on the inside of the

clump• Different from those on the

outside

• Cells inside begin to further pack themselves together and form a mass of cells called the inner cell mass (ICM), located at one end of the embryo

ICM

Blastcoele

Morula-stageembryo

Blastocyst-stageembryo

Early embryonic development

• The ICM – Develops into the fetus

• The outer layer of cells lining the zona pellucida– Trophoblast

• Placenta

– Formation of a fluid-filled cavity

• Blastcoele

• Blastocyst

ICM

Blastcoele

Morula-stageembryo

Blastocyst-stageembryo

Early embryonic development

• Cells in the ICM and trophoblast – Continue to divide– Blastacoele continues to

accumulate fluid

• Hatching– Floats freely until it

attaches itself within lumen of the uterus

Hatched blastocystZona

Attachment and establishment of pregnancy

• After hatching – Rapid growth and development phase.

• In cows, the blastocyst begins to rapidly elongate around 13 days after estrus, transforming from an ~3 mm spherical blastocyst into a long, thread-like form (around 25 cm in length) in 3 to 4 days

– The elongation of the bovine embryo• Due to rapid proliferation of trophoblast cells • Cells in the ICM divide slowly during elongation

ICM

ICM

Embryo

Placenta

Attachment and establishment of pregnancy

• Cattle and sheep– Attachment of trophoblast to the uterine wall

• Superficial with some fusion between uterus and trophoblast cells

Inner cell mass

Trophoblast layer

Uterine endometrium

Implantation and establishment of pregnancy

• Conceptus (embryo plus placental tissue)– Produces interferon-tau

(IFN-) as it elongates• Prevents production of

PGF2 by endometrium of the uterus

IFN-IFN-IFN-

IFN-

PGF PGFPGF PGF

PGF PGFPGF

PGF

Uterinevein

Non-Pregnant

PregnantConceptus

Endometrium

Uterine vein

Endometrium

• Diversion of PGF2 secretion

– Pigs• Non-pregnant

– Endocrine factor

• Conceptus– Divert secretion(exocrine)

– Estradiol• Increased production during 11-12 days post

coitus– Conceptus

• Diversion of PGF2 secretion– Local factor rather than systemic factor

• Conceptus must be present in both uterine horns

Secretion of luteotropic substances

• Species with passive luteolysis– Primates

• Secretion of glycoprotein hormone

– Syncytiotropoblast

• Human chorionic gonadotropin (hCG)

– Basis of pregnancy test

– Secretion begins around 10 days after ovulation

• hCG– Luteotropic hormone

• LH-like activity• Binds to LH receptors in the CL

– Maintenance of progesterone production– Increased lifespan during early stage of pregnancy

– Production• Peaks around 9 to 14 weeks of pregnancy

– CL loses its function during this time– Switch in steroidogenesis (placenta)

• Declines gradually thereafter

• Neuroendocrine system– Rodents and rabbits– Coitus as stimulus

• Physical contact• Physical stimulation of reproductive tract

(cervix)• Release of prolactin by the anterior pituitary

gland

• Neuroendocrine system– Prolactin

• Luteotropic hormone• Switch to placental hormones

– Placental lactogen

– CL• Eventually dies

– Steroid production by placenta

• Horses– Recognition of pregnancy

• Movement of embryo within the uterus– 12-14 times a day during day 12-14 of pregnancy– Eventual lock-down of the embryo

– Production of glycoprotein• eCG• Cause luteinization of the large follicle

– Formation of secondary CL

• FSH-like activity in other mammals

– Loss of both CLs• Placental progestigens