Exp Clin Endocrinol Diabetes 2008; 116(7): 393-403
DOI: 10.1055/s-2008-1042409
Review

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The Endocrinology of Equine Parturition

A. L. Fowden 1 , A. J. Forhead 1 , J. C. Ousey 2
  • 1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG
  • 2The Equine Fertility Unit, Mertoun Paddocks, Newmarket, Suffolk, CB8 9BH
Further Information

Publication History

received 05.12.2007 first decision 20.12.2007

accepted 15.01.2008

Publication Date:
25 March 2008 (online)

Abstract

Delivery of viable young requires co-ordination of fetal maturation with the onset of labour at term. In turn, this depends on a cascade of fetal and maternal endocrine events. The sequence of these events is broadly similar in most mammals but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species. In most farm animals, maternal progesterone (P4) levels decline and oestrogen levels increase in the last 5–10 days before delivery in response to activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis and increased fetal cortisol concentrations. This cortisol surge is also responsible for fetal maturation and increasing uteroplacental prostaglandin (PG) synthesis. In the mare, there is little, if any, P4 in the maternal plasma during late gestation and both progestagens and oestrogens are produced by a feto-placental unit which uses precursors supplied by the fetus to synthesise a range of C21 and C18 steroids, many of which are unique to the horse. Regulation of uterine quiescence and activation is, therefore, complex in the mare near term. Indeed, total progestagen concentrations rise and total oestrogen levels fall in the mare during the last 20–30 days of gestation and only show the changes typical of impending parturition in other species in the last 24–48 h before delivery. Fetal cortisol concentrations also rise late in gestation in the horse compared to other species. In common with other species, the prepartum endocrine cascade appears to begin in the fetal horse with activation of the fetal HPA axis but, initially, the primary product of the fetal equine adrenal appears to be pregnenolone (P5) and not cortisol. This leads to increased progestagen production by the uteroplacental tissues, which maintains uterine quiescence in the face of increasing uterine stretch caused by the rapidly growing fetus. Very close to term in association with increasing fetal ACTH levels, the fetal equine adrenals appear to switch to producing cortisol. This late cortisol surge induces a period of rapid fetal maturation and may also contribute to increased uteroplacental oestradiol-17β and PG production. The fall in P5 availability may reduce uteroplacental progestagen production and lift the block on myometrial contractility. Finally, increased PG secretion activates myometrial contractions, which stimulate oxytocin release via a neuroendocrine reflex. The endocrine regulation of equine parturition, therefore, involves progestagens, oestrogens, PGs and oxytocin as in other species. However, further studies are required to establish the causes and consequences of the rise and fall in maternal progestagens and the extent to which initiation of equine labour depends on the fetal HPA axis.

References

  • 1 Allen WR, Wilsher S, Turnbull C, Stewart F, Ousey J, Rossdale PD, Fowden AL. The influence of maternal size on placental, fetal and postnatal growth in the horse. II. Endocrinology of pregnancy.  J Endocrinol. 2002;  172 237-246
  • 2 Alm CC, Sullivan JJ, First NL. The effect of a corticoid (dexamethasone), progesterone, oestrogen and prostaglandin F2 α on gestation length in normal and ovariectomised mares.  J Reprod Fert Suppl. 1975;  23 637-640
  • 3 Barnes RJ, Nathanielsz PW, Rossdale PD, Comline RS, Silver M. Plasma progestagens and oestrogens in fetus and mother in late gestation.  J Reprod Fert Suppl. 1975;  23 617-623
  • 4 Bloomfield FH, Oliver MH, Hawkins P, Holloway AC, Campbell M, Gluckman PD, Harding JE, Challis JRG. Periconceptual under-nutrition in sheep accelerates maturation of the fetal hypothalamic-pituitary-adrenal axis in late gestation.  Endocrinology. 2004;  145 4278-4285
  • 5 Brendemenhl JP, Williams MA, Boosinger TR, Ruffin DC. Plasma progestagen, tri-iodothyromine and cortisol concentrations in postdate gestation foals exposed in utero to the tall fescue endophyte Acremonium coenophialum.  Biol Reprod Monograph. 1995;  1 53-59
  • 6 Browne ES, Wright BE, Porter JR, Svec F. Dehydroepiandrosterone: antiglucocorticoid action in mice.  Am J Med Sci. 1992;  303 366-371
  • 7 Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm.  Endo Rev. 2000;  21 515-550
  • 8 Chavatte P, Holton D, Ousey JC, Rossdale PD. Biosynthesis and possible biological roles of progestagens during equine pregnancy and in the newborn foal.  Equine Vet J Suppl. 1997;  24 89-95
  • 9 Chavatte P, Rossdale PD, Tait AD. 11β hydroxysteroid dehydrogenase (11βHSD) in equine placenta.  Am Assoc Equine Pract. 1995a;  41 264-265
  • 10 Chavatte P, Rossdale PD, Tait AD. Corticosteroid synthesis by the equine fetal adrenal.  Biol Reprod Monograph. 1995b;  1 13-20
  • 11 Chavatte-Palmer P, Duchamp G, Palmer E, Ousey JC, Rossdale PD, Lombes M. Progesterone, oestrogen and glucocorticoid receptors in the uterus and mammary glands of mares from mid to late gestation.  J Reprod Fert Suppl. 2000;  56 661-672
  • 12 Christiansen D, Olsen G, Smith J. The use of betamethasone to advance fetal maturation in the equine.  Havemeyer Foundation Monograph Series. 2006;  19 19-20
  • 13 Clarke KA, Ward JW, Forhead AJ, Giussani DA, Fowden AL. Regulation of 11β-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by cortisol.  J Endocrinol. 2002;  172 527-534
  • 14 Cox JE. Oestrone and equilin in the plasma of the pregnant mare.  J Reprod Fert Suppl. 1975;  23 463-468
  • 15 Cudd TA, Le Blanc M, Silver M, Norman W, Madison J, Keller-Wood M, Wood CE. Ontogeny and ultradrian rhythms in adrenocorticotropin and cortisol in the late gestation fetal horse.  J Endocrinol. 1995;  144 271-283
  • 16 Daels PF, Besoquet B, Hansen B, Mohammed H, Odensvik K, Kindahl H. Effect of progesterone on prostaglandin F2 alpha secretion and outcome of pregnancy during cloprostenol-induced abortion in mares.  Am J Vet Res. 1996;  57 1331-1337
  • 17 Davies Morel MCG, Newcombe JR, Holland SJ. Factors affecting gestation length in the Thoroughbred mare.  Anim Reprod Sci. 2002;  75 175-185
  • 18 Edwards LJ, MacMillen IC. Impact of maternal under-nutrition during the periconceptional period, fetal number and fetal sex on the development of the hypothalamic-pituitary-adrenal axis in sheep during late gestation.  Biol Reprod. 2002;  66 1562-1569
  • 19 Foster S, Marshall D, Houghton E, Gower DB. Investigations into the biosynthetic pathways for classic and Ring B unsaturated oestrogens in equine placental preparations and allantochoriotic tissues.  J Steroid Biochem Mol Biol. 2002;  82 401-411
  • 20 Fowden AL, Silver M. Effect of inhibiting 3β-hydroxysteroid dehydrogenase on plasma progesterone and other steroids in the pregnant mare near term.  J Reprod Fert Suppl. 1987;  35 539-545
  • 21 Fowden AL, Silver M. Comparative development of the pituitary-adrenal axis in the fetal foal and lamb.  Reprod Dom Anim. 1995;  30 170-177
  • 22 Fowden AL, Forhead AJ. Endocrine mechanisms of intrauterine programming.  Reproduction. 2004;  127 515-526
  • 23 Fowden AL, Comline RS, Silver M. Insulin secretion and carbohydrate metabolism during pregnancy in the mare.  Equine Vet J. 1984;  16 239-246
  • 24 Fowden AL, Forhead AJ, White KL, Taylor PM. Equine uteroplacental metabolism at mid and late gestation.  Exp Physiol. 2000;  85 539-545
  • 25 Fowden AL, Li J, Forhead AJ. Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance?.  Proc Nutr Soc. 1998;  57 113-122
  • 26 Fowden AL, Ralph M, Silver M. Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation.  Exp Clin Endo. 1994;  102 212-221
  • 27 Haluska GJ, Currie WB. Variation in plasma concentrations of oestradiol-17β and their relationship to those of progesterone, 13,14 dihydro-15-keto-prostaglandin F2 α and oxytocin across pregnancy and at parturition in pony mares.  J Reprod Fert. 1988;  84 635-646
  • 28 Haluska GJ, Lowe JE, Currie WB. Electromyographic properties of the myometrium correlated with the endocrinology of the pre-partum and post-partum periods and parturition in pony mares.  J Reprod Fert Suppl. 1987;  35 553-564
  • 29 Hamon M, Clarke SW, Houghton E, Fowden AL, Silver M, Rossdale PD, Ousey JC, Heap RB. Production of 5α-dihydroprogesterone during late pregnancy in the mare.  J Reprod Fert Suppl. 1991;  44 529-535
  • 30 Han X, Fowden AL, Silver M, Holdstock N, MacGladdery AJ, Ousey JC, Allen WR, Rossdale PD, Challis JRG. Immunohistochemical localisation of steroidogenic enzymes and phenylethanolamine N-methyl-transferase (PMNT) in the adrenal gland of the fetal and newborn foal.  Equine Vet J. 1995a;  27 140-146
  • 31 Han X, Rossdale PD, Ousey JC, Holdstock NB, Allen WR, Silver M, Fowden A, MacGladdery AJ, Labric F, Belanger A, Ensor CM, Tai H-H, Challis JRG. Localisation of 15-hydroxy prostaglandin dehydrogenase (PGDH) and steroidogenic enzymes in equine placenta.  Equine Vet J. 1995b;  27 334-339
  • 32 Holtan DW, Houghton E, Slver M, Fowden AL, Ousey J, Rossdale PD. Plasma progestagens in the mare, fetus and newborn foal.  J Reprod Fert Suppl. 1991;  44 517-528
  • 33 Jackson SA, Squires EL, Nett TM. The effect of exogenous progestins on endogenous progesterone secretion in pregnant mares.  Theriogenology. 1986;  25 275-279
  • 34 Janowski T, Zduñczyk S, Malecki-Tepicht J, Barañski W, Raœ A. Mammary secretion of oestrogens in the cow.  Domest Anim Endocrinol. 2002;  23 25-137
  • 35 Jeffcott LB, Rossdale PD. A critical review of current methods for induction of parturition in the mare.  Equine Vet J. 1977;  9 208-215
  • 36 Jochle W. Corticosteroid-induced parturition in domestic animals.  Ann Rev Pharmacol. 1973;  13 33-55
  • 37 Kitts DD, Anderson GB, Bon Durant RG, Stabenfeldt GH. Temporal withdrawal patterns of Δ4C-21 steroids in coexisting, genetically dissimilar twin lamb fetuses throughout late gestation.  Endocrinology. 1984;  114 703-711
  • 38 Klonisch T, Homback-Klonisch S. Review: Relaxin expression at the fetal-maternal interface.  Reprod Dom Anim. 2000;  35 149-152
  • 39 Leadon DP, Rossdale PD, Jeffcott , Allen WR. A comparison of agents for inducing parturition in the pre-viable and premature periods of gestation.  J Reprod Fert Suppl 1983. 1982;  32 597-602
  • 40 Liggins GC. The role of cortisol in preparing the fetus for birth.  Reprod Fert Dev. 1994;  6 141-150
  • 41 Lofgren M, Holst J, Bäckström T. Effects in vitro of progesterone and two 5α reduced progestins, 5α pregnane,-3,20-dione and 5α pregnane-3α-ol-20-one, on contracting human myometrium at term.  Acta Obstet Gyneal Scand. 1992;  71 28-33
  • 42 Lye SJ, Ou C-W, Teoh T-G, Erb G, Stevens Y, Casper R, Patel FA, Challis JRG. The molecular basis of labour and tocolysis.  Fetal Matern Med Rev. 1998;  10 121-136
  • 43 Macpherson ML. Treatment strategies for mares with placentitis.  Theriogenology. 2005;  64 528-534
  • 44 Marshall DE, Dumasia MC, Wooding P, Gower DB, Houghton E. Studies into aromatase activity associated with fetal allantochorionic and maternal endometrial tissues of equine placenta. Identification of metabolites by gas chromatography mass spectrometry.  J Steroid Biochem Mol Biol. 1996;  59 281-296
  • 45 Marshall DE, Gower DB, Silver M, Fowden AL, Houghton E. Cannulation in situ of equine umbilica. Identification by gas chromatography-mass spectrometry (GC-MS) of differences in steroid content between arterial and venous supplies to and from the placental surface.  J Steroid Biochem Mol Biol. 1999;  68 219-228
  • 46 MacGlothlin JA, Lester GD, House PJ, Thomas M, Pablo L, Hawkins DL, Le Blanc MM. Alteration in uterine contractility in mares with experimentally induced placentitis.  Reproduction. 2004;  127 57-66
  • 47 Moss GE, Estergreen VL, Becker SR, Grant BD. The source of 5α-pregnanes that occur during gestation in mares.  J Reprod Fert Suppl. 1979;  27 511-519
  • 48 Mostl E. The horse feto-placental unit.  Exp Clin Endo. 1994;  102 166-168
  • 49 NIH Consensus Development Conference . Effects of corticosteroid for fetal maturation on perinatal outcomes.  J Am Med Assoc. 1995;  273 413-418
  • 50 O’Donnell LJ, Sheenan BR, Henry JM, Thatcher MJ, Thatcher WW, Le Blanc MM. 24-hour secretion patterns of plasma oestradiol-17β in pony mares in late gestation.  Reprod Dom Anim. 2003;  38 233-235
  • 51 Ousey JC. Perinatal endocrinology in the mare and fetus.  Reprod Dom Anim. 2004;  39 222-231
  • 52 Ousey JC. Hormone profile and treatments in the late pregnant mare.  Vet Clin Equine. 2006;  22 724-747
  • 53 Ousey JC, Dudan F, Rossdale PD. Preliminary studies of mammary secretions in the mare to assess foetal readiness for birth.  Equine Vet J. 1984a;  16 259-263
  • 54 Ousey JC, Dudan F, Rossdale PD. Effects of fluprostenol administration in mares during late gestation.  Equine Vet J. 1984b;  16 264-269
  • 55 Ousey JC, Forhead AJ, Rossdale PD, Grainger L, Houghton E, Fowden AL. The ontogeny of uteroplacental progestagen production in pregnant mares during the second half of gestation.  Biol Reprod. 2003;  69 540-548
  • 56 Ousey JC, Freestone N, Fowden AL, Mason WJ, Rossdale PD. The effects of oxytocin and progestagens on myometrial contractility in vitro during equine pregnancy.  J Reprod Fert Suppl. 2000;  56 681-689
  • 57 Ousey JC, Houghton E, Grainger L, Rossdale PD, Fowden AL. Progestagen profiles during the last trimester of gestation in Thoroughbred mares with normal and compromised pregnancies.  Theriogenology. 2005;  63 1844-1856
  • 58 Ousey JC, Rossdale PD, Dudan FE, Fowden AL. The effects of intrafetal ACTH administration on the outcome of pregnancy in the mare.  Reprod Fert Dev. 1998;  10 359-367
  • 59 Ousey JC, Rossdale PD, Palmer L, Grainger L, Houghton E. Effects of maternally administered Depot ACTH1–2 α on fetal maturation and the timing of parturition in the mare.  Equine Vet J. 2000;  32 489-496
  • 60 Ousey JC, Rossdale PD, Palmer L, Houghton E, Grainger L, Fowden AL. Effects of progesterone administration to mares during late gestation.  Theriogenology. 2002;  58 793-795
  • 61 Palmer E, Chavatte-Palmer P, Duchamp G, Levy I. Lack of effect of clenbuterol for delaying parturition in late pregnant mares.  Theriogenology. 2002;  58 797-799
  • 62 Pashen RL. Low doses of oxytocin can induce foaling at term.  Equine Vet J. 1980;  12 85-87
  • 63 Pashen RL. Maternal and foetal endocrinology during late pregnancy and parturition in the mare.  Equine Vet J. 1984;  16 233-238
  • 64 Pashen RL, Allen WR. The role of the fetal gonads and placenta in steroid production, maintenance of pregnancy and parturition in the mare.  J Reprod Fert Suppl. 1979;  27 499-509
  • 65 Pashen RL, Sheldrick EL, Allen WR, Funt APF. Dehydroepiandrosterone synthesis by the fetal foal and its importance as an oestrogen precursor.  J Reprod Fert Suppl. 1982;  32 389-297
  • 66 Platt H. Growth of the equine fetus.  Equine Vet J. 1984;  16 247-252
  • 67 Poore KR, Young IR, Canny BJ, Jacobs RA, Thorburn GD. Studies on the role of adrenocorticotrophin (ACTH) in the regulation of adrenal responsiveness and the timing of parturition in the fetal sheep.  J Endocrinol. 1998;  158 161-171
  • 68 Raeside JL, Liphap RM. Patterns of urinary oestrogen excretion in individual pregnant mares.  J Reprod Fert Suppl. 1975;  23 469-475
  • 69 Rigby S, Love C, Carpenter K, Varner D, Blanchard T. Use of prostaglandin E2 to ripen the cervix of the mare prior to induction of parturition.  Theriogenology. 1998;  15 897-904
  • 70 Rossdale PD, Silver M. The concept of readiness for birth.  J Reprod Fert Suppl. 1982;  32 507-510
  • 71 Rossdale PD, MacGladdery AJ, Ousey JC, Holdstock N, Grainger L, Houghton E. Increase in plasma progestagen concentrations in the mare after foetal injection with CRH, ACTH or betamethasone in late gestation.  Equine Vet J. 1992;  24 347-350
  • 72 Rossdale PD, Ousey JC, Cottrill CM, Chavatte P, Allen WR, MacGladdery AJ. Effects of placental pathology on maternal plasma progestagen and mammary secretion calcium concentrations and on neonatal adrenocortical function in the horse.  J Reprod Fert Suppl. 1991;  44 579-590
  • 73 Schutzer WE, Holtan DW. Steroid transformation in pregnant mares: metabolism of exogenous progestins and unusual metabolic activity in vivo and in vitro.  Steroids. 1996;  61 94-99
  • 74 Schutzer WE, Kerby JL, Holton DW. Differential effect of Trilostane on the progestin milieu in the pregnant mare.  J Reprod Fert. 1996;  107 241-248
  • 75 Short RV. Progesterone in blood: IV Progesterone in the blood of mares.  J Endocrionol. 1959;  19 207-210
  • 76 Silver M, Fowden AL. Uterine prostaglandin F metabolite production in relation to glucose availability in late pregnancy- the possible influence of diet on the time of delivery in the mare.  J Reprod Fert Suppl. 1982;  32 511-519
  • 77 Silver M, Fowden AL. Prepartum adrenocortical maturation in the fetal foal: responses to ACTH1–24.  J Endocrinol. 1994;  142 417-425
  • 78 Silver M. Prenatal maturation, the timing of birth and how it may be regulated in domestic animals.  Exp Physiol. 1990;  75 285-307
  • 79 Silver M. Placental progestagens in the sheep and horse and the changes leading to parturition.  Exp Clin Endo. 1994;  102 203-211
  • 80 Silver M, Barnes RJ, Comline RS, Fowden AL, Clover L, Mitchell MD. Prostaglandins in maternal and fetal plasma and in allantoic fluid during the second half of gestation in the mare.  J Reprod Fert Suppl. 1979;  27 531-539
  • 81 Silver M, Fowden AL, Knox J, Ousey JC, Cash R, Rossdale PD. Relationship between circulating tri-iodothyronine and cortisol in the perinatal period in the foal.  J Reprod Fert Suppl. 1991;  44 619-626
  • 82 Silver M, Ousey JC, Dudan FE, Fowden AL, Knox J, Cash RSG, Rossdale PD. Studies on equine prematurity 2. Post-natal adrenocortical activity in relation to plasma ACTH and catecholamine levels in term and premature foals.  Equine Vet J. 1984;  16 275-286
  • 83 Stewart DR, Kindahl H, Stabenfeldt GH, Hughes JP. Concentrations of 15-keto-13,14 dihydroprostaglandin F2 α in the mares during spontaneous and oxytocin induced parturition.  Equine Vet J. 1984;  16 270-274
  • 84 Stewart DR, Addiego LA, Pascoe DR, Haluska GJ, Pashen R. Breed differences in circulating equine relaxin.  Biol Reprod. 1992;  46 648-652
  • 85 Tait AD, Hodge LC, Allen WR. The biosynthesis of 3β-hydroxy-5,7-androstadien-17-one by the fetal horse gonad.  FEBS Lett. 1985;  182 107-110
  • 86 Thorburn GD. A speculative review of parturition in the mare.  Equine Vet J Suppl. 1993;  14 41-49
  • 87 Vivrette SL, Kindahl H, Munro CJ, Roser JF, Stabenfeldt GH. Oxytocin release and its relationship to dihydro-15-keto-PGF2 α and arginine vasopressin release during parturition and to suckling in postpartum mares.  J Reprod Fert. 2000;  119 347-357
  • 88 Vivrette SL, Kindahl H, Muro CJ, Roser J, Stabenfeldt GH. Effects of flunixin meglumine on pituitary effluent oxytocin, arginine vasopressin and 15-keto dihydroprostaglandin F2 α concentration and clinical parturient events during oxytoxin-induced parturition in mares.  Biol Reprod Monograph. 1995;  1 69-75
  • 89 Webb PD, Stevens DH. Development of the adrenal cortex in the fetal foal: an ultrastructural study.  J Dev Physiol. 1981;  3 59-73

Correspondence

A.L. Fowden

Department of Physiology

Development and Neuroscience

University of Cambridge

Downing Street

Cambridge

CB2 3EG

Phone: +44/0/1223 33 38 55

Fax: +44/0/1223 33 38 40

Email: alf1000@cam.ac.uk

    >