Expression of steroidogenic enzymes in placentome of ewes with pregnancy toxemia after two parturition induction methods


Published: Jul 4, 2023
Updated: 2023-07-04
Keywords:
Parturition induction Ewes Pregnancy Toxemia Aglepristone Dexamethasone
G Özalp
https://orcid.org/0000-0003-4694-6937
CT Ortaç
B Bozkurt
A Rişvanlı
A Aktar
A Yavuz
Y Korlu
İ Şeker
Abstract

The regulation pattern of important enzymes in placental steroidogenesis and prostaglandins in ewes with pregnancy toxemia is reviewed. The alterations of gene expressions after the administration of aglepristone and dexamethasone are also discussed. Four healthy and 22 ewes with pregnancy toxemia were included to the study. Group AG (n=9) and Group DEX (n=9) in which ewes were injected twice with 10 mg/kg of aglepristone and once with 5 ml dexamethasone, respectively; whereas negative control [Group CG (n=4)] and pregnancy toxemia [Group PT (n=4)] groups received no treatment for parturition induction. Placentomes were collected either right after parturition or C-section. mRNA extraction from total placentome, caruncle, cotyledon and caruncle part of placentomes was carried out and Real-Time PCR was performed. Serum samples were collected and cortisol, PGFM, PGE2 and estrone sulfate concentrations were measured after treatments until parturition. The lowest mRNA expressions of steroidogenic enzymes were detected in group PT. Interestingly similar expression pattern of steroidogenic enzymes in group AG was as similar as group PT. No difference was found in expressions of 3βHSD and CYP19. PTGS2/COX2 and PGFS mRNA expressions were statistically different between groups AG-DEX and in caruncle between groups, respectively (P<0.005). Significant difference could clearly be observed in EP3 expression in caruncle of DEX and AG compared to CG (P<0.005); however PTGES, EP1, EP2 and EP4 expressions were not statistically different among groups (P>0,05). Ostrone sulfate, PGE2 and PGFM concentrations were statistically different according to the sampling time between groups however no difference was observed in cortisol. The present study has suggests that the endocrinologic pathway controlling parturition is clearly different in ewes with pregnancy toxemia. Spontaneous parturition could occur as a consequence of immune and inflammatory processes, which could be activated by by-products of fat metabolism. Dexamethasone applications has mimicked normal parturition, however the gene expression regulations, controlling uterine contractions, are observed as similar as group PT. Probably expressions of EP1 and tissue-specific counter-expressions of cervical EP genes could refer the pathogenesis of insufficient cervical dilatation, observed in pregnancy toxemia and dexamethsone applications. 

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Barbagianni MS, Giannenas E, Papadopoulos E, Petridis IG, Spanos SA, Gouletsou PG, Valasi I, Fthenakis FC (2015) Pregnancy toxaemia in ewes: Development of an experimental modeland potential interactions with gastrointestinal nematode infections. Small Ruminant Res 133: 102-107.
Barros RP, Morani A, Moriscot A, Machado UF (2008) Insulin resistance of pregnancy involves estrogen-induced repression of muscle GLUT4. Mol Cell Endocrinol 25: 24-31.
Behrman RE, Butler AS (2007) Biologic Pathways Leading to Pretrem Birth. In: Preterm Birt. Causes, Consequences, and Prevention. The National Academies of Science Engineering Medicine, The National Academies Press: pp 169-772.
Bloomfield FH, Oliver MH, Giannoulias CD, Gluckman PD, Harding JE, Challis JR (2003) Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring. Endocrinology 144: 2933–2940.
Bloomfield FH, Oliver MH, Hawkins P, Holloway AC, Campbell M, Gluckman PD, Harding JE, Challis JR (2004) Periconceptional undernutrition in sheep accelerates maturation of the fetal hypothalamic-pituitary-adrenal axis in late gestation. Endocrinology 145: 4278–4285.
Boileau MJ (2008) Pregnancy toxemia in small ruminants. ACVIM FAIM Short Course: Pregnancy toxemia; 2008.
Boland MP, Crosby TF, Gordon I (1982) Induction of lambing: comparison of the effects of prostaglandin, oestradiol benzoate and dexamethasone. J Agri Sci Camb 98: 391-394.
Braun T, Challis JR, Newnham JP, Sloboda DM (2013) Early-life glucocorticoid exposure: the hypothalamic–pituitary–adrenal axis, placental function, and long-term disease risk. Endocr Rev 34, 885-916.
Challis JR (1971) Sharp increase in free circulating oestrogens immediately before parturition in sheep. Nature 229: 208.
Challis JRG, Lye SJ (1994) Parturition, Knobil. In: Neill JD, Eds. The Physiology of Reproduction. Raven Press Ltd: pp 985–1031.
Challis JRG, Lye SJ, Gibb W (1997) Prostaglandins and parturition. Ann NY Acad Sci 828: 254–267.
Challis JRG, Matthews SG, Gibb W, Lye SJ (2000) Endocrine and paracrine regulation of birth at term and preterm. Endocrine Reviews 21: 514–550.
Challis JR, Sloboda D, Matthews SG, Holloway A, Alfaidy N, Patel FA, Whittle W, Fraser M, Moss TJ, Newnham J (2001) The fetal placental hypothalamic–pituitary–adrenal (HPA) axis, parturition and post natal health. Mol Cell Endocrinol 185, 135-44.
Duehlmeier R, Fluegge I, Schwert B, Ganter M (2013) Insulin sensitivity during late gestation in ewes affected by pregnancy toxemia and in ewes with high and low susceptibility to this disorder. J Vet Intern Med 27: 359-366.
Flint APF, Anderson ABM, Steele PA, Turnbull AC (1975) The mechanism by which foetal cortisol controls the onset of parturition in the sheep. Biochem Soc Trans 3: 1189–1194.
Ford EJ, Evans J, Robinson I (1990) Cortisol in pregnancy toxemia of sheep. Br Vet J 146: 539-542.
France JT, Mason JI, Magness RR, Murry BA, Rosenfeld CR (1987) Ovine placental aromatase: Studies of activity levels, kinetic characteristics and effects of aromatase inhibitors. J Steroid Biochem 28: 155-160.
France JT, Magness RR, Murry BA, Rosenfeld CR, Mason JI (1998) The regulation of ovine placental steroid 17 alpha-hydroxylase and aromatase by glucocorticoid. Mol Endocrinol 2: 193-199.
Gyomorey S, Lye SJ, Gibb W, Challis JRG (2000) The fetal to maternal progression of PGHS-2 expression in ovine intrauterine tissues during the course of labor. Biol Reprod 62: 797–805.
Harman EL, Slyter AL (1980) Induction of parturition in the ewe. J Anim Sci 50: 391-393.
Huang S, Pang Y, Yan J, Lin S, Zhao Y, Lei L, Yan L, Li R, Ma C, Qiao J (2016) Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome. Sci Rep 6: 26205.
Hunt ER (1976)a Treatment of pregnancy toxaemia in ewes by induction of parturition. Aust Vet J 52: 338-339.
Hunt ER (1976)b Treatment of pregnancy toxaemia in ewes by induction of parturition. Aust Vet J 52: 540.
Kastelic JP, Cook RB, McMahon LR, McAllister TA, McClelland LA, Cheng KJ (1996) Induction of parturition in ewes with dexamethasone or dexamethasone and cloprostenol. Can Vet J 37: 101–102.
Konopka CK, Glanzner WG, Rigo ML, Rovani MT, Comim FV, Gonçalves PB, Morais EN, Antoniazzi AQ, Mello CF, Cruz IB (2015) Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium. Genet Mol Res 14: 10877-10887.
Lewis GS, Jenkins PE, Fogwell RL, Inskeep EK(1978) Concentrations of prostaglandins E2 and F2 alpha and their relationship to luteal function in early pregnant ewes. J Anim Sci 47: 1314- 1323.
Liggins GC, Grieves S, Bangham DR, Calam DH, Parsons JA, Robinson CJ (1971) Possible role for prostaglandin F2α in parturition in sheep. Nature 232: 629–631.
Long NM, Tuersunjiang N, George LA, Lemley CO, Ma Y, Murdoch WJ, Nathanielsz PW, Ford SP (2013) Maternal nutrient restriction in the ewe from early to midgestation programs reduced steroidogenic enzyme expression and tended to reduce progesterone content of corpora lutea, as well as circulating progesterone in nonpregnant aged female offspring. Reprod Biol Endocrinol 11: 34.
Lye SJ (1994) The initiation and inhibition of labor. Toward a molecular understanding. Semin Reprod Med 12: 284-297.
Ma X, Wu WX, Nathanielsz PW (1999) Differential regulation of prostaglandin EP and FP receptors in pregnant sheep myometrium and endometrium during spontaneous term labor. Biol Reprod 61; 1281–1286.
Mason JI, France JT, Magness RR, Murry BA, Rosenfeld CR (1989) Ovine placental steroid 17α-hydroxylase/C-17,20-lyase, aromatase and sulphatase in dexamethasone-induced and natural parturition. J Endocrinol 122: 351–359.
McClymont GL, Setchell BP (1956) Ovine pregnancy toxaemia. IV. Insulin induced hypoglycaemic encephalopathy in the sheep and its implications as regards the pathogenesis of the disease. Aust Vet J 32: 97-109
McClymont GL, Setchell BP (1995) Ovine pregnancy toxemia. II. Experimental therapy with glycerol and glucose. Aust Vet J 31: 170-174.
McLaren WJ, Young IR, Wong MH, Rice GE (1996) Expression of prostaglandin G/H synthase-1 and -2 in ovine amnion and placenta following glucocorticoid-induced labour onset. J Endocrinol 151: 125-135.
McKeown K, Adamson L, Bocking A, Challis JRG, Fraser M, Rurak D, Scott C, Small C, Lye SJ (1999) Altered fetal pituitary-adrenal function in the ovine fetus treated with RU486 and meloxicam (MEL), an inhibitor of prostaglandin synthase-2. J Soc Gynecol Invest 7: 114.
Negishi M, Sugimoto Y, Ichikawa A (1995) Molecular mechanisms of diverse actions of prostanoid receptors. Biochim Biophys Acta 1259: 109–120.
Nestler JE, Jakubowicz DJ (1996) Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 335: 617-623.
Özalp RG, Yavuz A, Orman A, Seker I, Udum-Kücüksen D, Rişvanlı A, Demiral OÖ, Wehrend A (2017) Parturition induction in ewes by a progesterone receptor blocker, aglepristone, and subsequent neonatal survival: Preliminary results. Theriogenology 87: 141-147.
Özalp GR, Yavuz A, Seker I, Udum-Küçüksen D, Risvanlı A, Korlu Y (2018) Evaluation of an alternative treatment protocol by aglepristone to induce parturition in ewes with an experimental model of early pregnancy toxemia. Theriogenology 116: 112-118.
Palliser HK, Ooi GT, Hirst JJ, Rice GE, Dellios NL, Escalona RM, Young IR (2004) Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep. J Endocrinol 180: 469–477.
Palliser HK, Hirst JJ, Ooi GT, Rice GE, Dellios NL, Escalona RM, Parkington HC, Young IR (2005) Prostaglandin E and F receptor expression and myometrial sensitivity at labor onset in the sheep. Biol Reprod 72: 937–943.
Palliser HK, Hirst JJ, Rice GE, Ooi GT, Dellios NL, Escalona RM, Young IR (2006) Labor-associated regulation of prostaglandin E and F synthesis and action in the ovine amnion and cervix. J Soc Gynecol Investig 13: 19-24.
Radostits OM, Gay CC, Hinchcliff KW, Constable PD (2007) Metabolic diseases, pregnancy toxemia in sheep. In: Veterinary Medicine. A Textbook of the Disease of Cattle, Horses, Sheep, Pigs and Goats. Elsevier: pp 1168-71.
Ranaweera A, Ford EJ, Samad AR (1979) The effect of triamcinolone acetonide on plasma glucose and ketone concentration and on the total entry rate of glucose in twin pregnant hypoglycaemic ketotic sheep. Res Vet Sci 26: 12-16.
Reynolds LP, Caton JS, Vonnahme KA, Redmer DA, Corbin CJ, Conley AJ (2010) Effects of maternal plane of nutrition, placental tissue type, and stage of gestation on 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and aromatase activity of sheep placenta. Biol Reprod 83: 121.
Rook JS (2000) Pregnancy Toxemia of ewes, does and beef cows. Veterinary Clinics of North America: Food Animal Practice 16: 293-317.
Root-Bernstein R, Podufaly A, Dillon PF (2014) Estradiol binds to insulin and insulin receptor decreasing insulin binding in vitro. Front Endocrinol (Lausanne) 5: 118.
Schuler G, Fürbass R, Klisch K (2018) Placental contribution to the endocrinology of gestation and parturition. Anim Reprod 15: 822-842.
Shenavai S, Preissing S, Hoffmann B, Dilly M, Özalp GR, Caliskan C, Seyrek-Intas K, Schuler G (2012) Investigations into the mechanisms controlling parturition in cattle. Reproduction 144: 279-292.
Smith MC, Sherman DM (1994) Goat Medicine, Philadelphia, Lea & Febiger: pp 546-549.
Smith GCS, Baguma-Nibasheka M, Wu WX, Nathanielsz PW (1998) Regional variations in contractile response to prostaglandins and prostanoid receptor messenger ribonucleic acid in pregnant baboon uterus. Am J Obstet Gynecol 70: 1545–1552.
Stormshak F, Bishop CV (2008) Board-invited review: estrogen and progesterone signaling: genomic and nongenomic actions in domestic ruminants. J Anim Sci 86: 299–315.
Tsang CP (1974) Changes in plasma levels of estrone sulfate and estrone in the pregnant ewe around parturition. Steroids 23: 855–868.
Vanselow J, Selimyan R, Fürbass R (2008) DNA methylation of placenta-specific Cyp19 promoters of cattle and sheep. Exp Clin Endocrinol Diabetes 116: 437-442.
Qin KN, Rosenfield RL (1998) Role of cytochrome P450c17 in polycystic ovary syndrome. Mol Cell Endocrinol 145: 111-121.
Watanabe K, Yoshida R, Shimizu T, Hayaishi O (1985) Enzymatic formation of prostaglandin F2α from prostaglandin H2 and D2. J Biol Chem 260: 7035–7041.
Whittle WL, Holloway AC, Lye SJ, Gibb W, Challis JRG (2000) Prostaglandin production at the onset of ovine parturition is regulated by both estrogen-independent and estrogen-dependent pathways. Endocrinology 141: 3783–3791.
Whittle WL, Patel FA, Alfaidy N, Holloway AC, Fraser M, Gyomorey S, Lye SL, Gibb W, Challis JRG (2001) Glucocorticoid regulation of human and ovine parturition: The relationship between fetal hypothalamic-pituitary-adrenal axis activation and intrauterine prostaglandin production. Biol of Reprod 64: 1019–1032.
Zamir S, Rozov A, Gootwine E (2009) Treatment of pregnancy toxaemia in sheep with flunixin meglumine. Vet Rec 165: 265-266.
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