BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw A man took his pregnant wife to the hospital to give birth. The doctor told them that they'd developed a new machine and asked if the couple would like to try it out. The machine could take some of the pain of childbirth from the mother and give it to the father to ease the mother's burden. Well, they thought that was a good idea, and decided to give it a try. The doctor initially set the machine on 10 percent, telling the man that even 10 percent was probably more pain than he'd ever experienced. But the husband was surprised at how little pain he was feeling, and asked the doctor to raise the level. The doctor increased it to 20 percent, and when the man still felt fine, he raised it to 50 and finally 100 percent. After it was all over, the man stood up, and stretched a little. Both he and his wife felt fine, and they shortly left the hospital to take the baby home. It was then that they found the mailman dead on their doorstep

Masters in Zoology Information Session When: Thursday 4th September 2014 1pm Where: Drummond room, ground floor Zoology Find out about masters in Zoology and potential projects. Meet and talk to potential supervisors. Department of ZOOLOGY

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw BIOL30001 Reproductive Physiology Parturition Geoff Shaw References EssRep7 Chapters 14-17 Austin & Short 2nd Edn Book 2 chap 4, The fetus and birth Thorburn, Hollingworth & Hooper (1991) The trigger for parturition in the sheep: fetal hypothalamus or placenta. J Developmental Physiology 15: 71-79 Leelan et al. (2003) Cytokines, Prostaglandins and Parturition—A Review. Placenta 24 supp A: S33-46. Jenkin G, Young IR. (2004) Mechanisms responsible for parturition; the use of experimental models. Anim Reprod Sci.82-83:567-81. Young IR, Renfree MB, Mesiano S, Shaw G, Jenkin G, Smith R (2011) The Comparative Physiology of Parturition in Mammals. In Hormones and Reproduction of Vertebrates - Vol 5: Mammals . pp 95-116. Ed. Norris, D. & Lopez, K. H.. Elsevier

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Birth A dog whelps and gives birth to puppies A cow calves and give birth to a calf A sow farrows and gives birth to piglets A ewe lambs and give birth to lambs A horse foals and give birth to a foal

BIOL30001 Reproductive Physiology The birth process Parturitition: Geoff Shaw transition: retain & nurture fetus  expel fetus synchrony parturition & fetal maturation fetal & maternal regulation of timing activation of myometrium softening of cervix timing – synchrony with fetal maturation Johnson & Everitt Fig 13.1

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Fetal maturation lung transition between amniotic fluid to air structural maturation surfactant production (cortisol induced) circulation placental to pulmonary gas exchange closure of foramen ovale & ductus arteriosus carbohydrate and fat reserves mobilisation of liver glycogen by cortisol fat reserves released by insulin & thyroxine until lactation established

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw The Myometrium circular and longitudinal muscle layers, blood vessels and connective tissue muscle cells hypertrophy during pregnancy electrical connection via gap junctions leading to coordinated contractions intracellular Ca++ activates contraction spontaneous pacemaker activity ® excitation threshold

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Hormones progesterone & oestradiol prostaglandins oxytocin nitric oxide (NO) relaxin

Progesterone & oestradiol BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Progesterone & oestradiol production by placenta and CL usually ¯ P4 &  E2 at birth P4 E2 PG ¯  OT receptor -  Ca++ influx -  Ca++ sequestration ­ - gap junctions - ­

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Prostaglandins E2 P4 Phospholipids + - produced in endometrium, myometrium and placenta PGF2a uterine contractions incr. release of Ca++ from intracellular stores PGE2 & F2a induce cervical ripening phospholipase A2 Arachidonic acid Cyclo-oxygenase (COX1, COX2) PGH2 PGE2 PGF2 PGD PGI2 TXA2 etc.

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Oxytocin produced by hypothalamus, released from posterior pituitary CL uterus induces uterine contractions increase Ca++ influx stimulate PG release release stimulated by cervical stimulation - Ferguson reflex OT neural signal cervical stretch

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Nitric Oxide NO - potent inhibitor of smooth muscle contraction Myometrium pregnancy: progesterone promotes  iNOS shut down NO production in labour Cervix activation of iNOS at term NO activates matrix metalloproteases

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Relaxin cytokine related to insulin produced in CL - released in late gestation softens (relaxes) connective tissue in cervix & pubic symphysis stimulates mammary development

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw goat fetal pituitary ACTH fetal adrenal fetal maturation C19 steroids oestrogens cortisol Aromatase PLACENTA PLACENTA maternal neurohypophysis PGF2 Corpus Luteum regression OT Ferguson reflex PG synthesis Progesterone withdrawal contractions MYOMETRIUM

Placental steroidogenic enzymes activated by cortisol BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw HO Cholesterol CH3 CH3 C=O C=O HO O D5-pregnenolone Progesterone 17a-hydroxylase CH3 CH3 C=O C=O OH OH Aromatase HO O 17a-OH-pregnenolone 17a-OH-progesterone 17-20-Lyase (17-20-Desmolase) O O O HO HO O Dehydroepiandrosterone (DHEA) Androstenedione Oestrone OH OH O HO Testosterone Oestradiol-17b

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw sheep fetal pituitary ACTH cortisol incr. sensitivity to ACTH at term fetal maturation fetal adrenal oestrogens 17 hydroxylase C17-C20 lyase Aromatase Progesterone PLACENTA PLACENTA maternal neurohypophysis OT Ferguson reflex P4 decrease as production redirected into E2 Progesterone withdrawal PG synthesis contractions MYOMETRIUM

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Birth in humans Somewhere on this globe, every ten seconds, there is a woman giving birth to a child. She must be found and stopped. --Sam Levenson

BIOL30001 Reproductive Physiology human Parturitition: Geoff Shaw fetal pituitary ACTH cortisol fetal maturation fetal adrenal CRF C19 steroids (largely DHAS) oestrogens PLACENTA Aromatase no 17-hydroxylase PLACENTA maternal neurohypophysis PGF2 CL regression Progesterone withdrawal PG synthesis iNOS OT Ferguson reflex MYOMETRIUM contractions

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw pH 7.35 Umb Art pH 7.2 pH 7.26 Fetal haemoglobin Bohr effect – pH change as CO2 ex-changed increases O2 transfer note: placenta highly metabolically active – uses 30% of O2 supplied Ut Art Umb Vein Ut Vein Johnson & Everitt Fig 12.2; table 12.1

Circulation before birth BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw Circulation before birth oxygenated blood draining from placenta mixes with depleted blood from body Lung is fluid filled and has low O2. It has constricted arterioles restricting blood flow FO LUNG BODY PLACENTA DA Most blood shunts through foramen ovale and ductus arteriosus.

Circulation after birth BIOL30001 Reproductive Physiology Circulation after birth Parturitition: Geoff Shaw increased flow into Left Atrium closes flap over Foramen ovale Oxygen opens capillaries in lung increasing blood flow FO closes LUNG BODY DA closes increased oxygenation of blood in ductus arteriosus causes contraction and closure

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw indicator of lung surfactant production Johnson & Everitt Fig 12.5

Actions of fetal adrenal glucocorticoids BIOL30001 Reproductive Physiology Actions of fetal adrenal glucocorticoids Parturitition: Geoff Shaw lung surfactant; water resorption central respiratory mechanisms metabolism glucose storage and gluconeogenesis endocrine induced insulin secretion induced adrenaline secretion conversion of T3 to T4 placental steroidogenesis blood switch from fetal to adult haemoglobin switch haematopoiesis to bone marrow salt balance stimulation of GFR and Na+ resorption ?activation of ANF lactogenesis ductal-lobule-alveolar growth in pregnancy

BIOL30001 Reproductive Physiology Parturitition: Geoff Shaw placenta FO RA LA body lung RV LV Ductus Arteriosus Sensitive to O2, closes when O2 increases Foramen Ovale Flap valve, closes when pressure in LA>RA RA RV LA LV body lung DA

Parturition Summary Process involves synchronised interactions between fetus and maternal system Transition from quiescent to active uterus (↓Prog, ↑E2; NO; PGF2α; OT; Fergusson reflex) Triggers vary between species Fetal triggers: adrenal cortisol Placental: PGE2; CRF Physiological maturation of cardiovascular system: gas exchange switch from placenta to lung