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 (PGF 2  ) Uterus Passive luteolysis –Loss of luteotropic agents

Active luteolysis Communication from uterus to ovary – Approximately 4 days before estrus, the uterus begins to produce PGF 2 , –PGF 2   diffuses into the bloodstream feeding the ovary bearing the CL (ovarian artery). PGF 2  Uterine vein Ovarian artery Large black arrows indicate direction of PGF 2  flow

From uterus to ovary –Interaction between PGF 2  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. PGF 2  Progesterone Oxytocin PGF 2 

From ovary to uterus (and back to the ovary) –Oxytocin Reaches the uterus and stimulates production of more PGF 2  –Increasing amount of estradiol from the large follicle Increased production of PGF 2  by uterus through increased sensitivity to oxytocin PGF 2  Progesterone Oxytocin PGF 2 

From ovary to uterus (and back to the ovary) –Positive feedback loop Uterine production of PGF 2  Production of oxytocin by the CL –Ultimately leads to corpus luteum regression Reinitiation of reproductive cycle PGF 2  Progesterone Oxytocin PGF 2 

Local regulation of reproductive cycle Progesterone production by CL –Begins to decline. –Initiated by increased production of PGF 2  –Increased production of PGF 2  Ablated when pregnancy has been initiated, resulting in continued Progesterone production by the CL and pregnancy maintenance PGF 2  Progesterone Pregnancy

Maternal recognition of pregnancy Two types –Anti-luteolytic Diversion of PGF 2  secretion Inhibition of PGF 2  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) Ampulla Isthmus 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-stage embryo Blastocyst- stage embryo

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-stage embryo Blastocyst- stage embryo

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 blastocyst Zona

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 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 PGF 2  by endometrium of the uterus IFN-  PGF Uterine vein Non-Pregnant Pregnant Conceptus Endometrium Uterine vein Endometrium

Diversion of PGF 2  secretion –Pigs Non-pregnant –Endocrine factor Conceptus –Divert secretion(exocrine) –Estradiol Increased production during days post coitus –Conceptus

Diversion of PGF 2  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 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