Animal Reproduction (AR)
http://animal-reproduction.org/article/doi/10.21451/1984-3143-AR2018-0056
Animal Reproduction (AR)
Conference Paper

Impact of thermal stress on placental function and fetal physiology

Sean W. Limesand, Leticia E. Camacho, Amy C. Kelly, Andrew T. Antolic

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Abstract

In ruminants, prolonged exposure to high ambient temperatures negatively affects placental development and function. The pursuing limitations in placental oxygen and nutrient supply between the mother and fetus slow fetal growth lowering birth weights and postnatal performance. The pregnant ewe is a long-standing animal model for the study of maternal-fetal interactions and is susceptible to naturally occurring heat stress, which causes fetal growth restriction. In the pregnant ewe, studies show that the fetus adapts to hyperthermia-induced placental insufficiency to preserve placental transport capacity of oxygen and nutrients. These adaptive responses are at the expense of normal fetal development and growth. Enlarged transplacental gradient for oxygen and glucose facilitates diffusion across the placenta, but develops by lowering fetal blood oxygen and glucose concentrations.  Fetal hypoxemia and hypoglycemia slow growth and alter their metabolic and endocrine profiles. Deficits in amino acids transport across the placenta are present but are overcome by reduced fetal clearance rates, likely due to fetal hypoxemia or endocrine responses to hypoxic stress. Here, we provide an overview of the performance limitations observed in ruminants exposed to heat stress during pregnancy, but we focus our presentation on the sheep fetus in pregnancies complicated by hyperthermia-induced placental insufficiency. We define the characteristics of placental dysfunction observed in the fetus of heat stressed ewes during pregnancy and present developmental adaptations in organogenesis, metabolism, and endocrinology that are proposed to establish maladaptive situations reaching far beyond the perinatal period.

Keywords

 heat stress, intrauterine growth restriction, placental insufficiency, sheep fetus.

References

Abdalla EB, Kotby EA, Johnson HD. 1993. Physiological responses to heat-induced hyperthermia of pregnant and lactating ewes Small Rumin Res, 11:125-134.

Ahmed BMS, Younas U, Asar TO, Dikmen S Hansen PJ, Dahl GE. 2017. Cows exposed to heat stress during fetal life exhibit improved thermal tolerance. J Anim Sci, 95:3497-3503.

Aldoretta PW, Carver TD, Hay WW Jr. 1998. Maturation of glucose-stimulated insulin secretion in fetal sheep. Biol Neonate, 73:375-386.

Allen RE, Merkel RA, Young RB. 1979. Cellular aspects of muscle growth: myogenic cell proliferation. J Anim Sci, 49:115-127.

Anderson AH, Fennessey PV, Meschia G, Wilkening RB, Battaglia FC. 1997. Placental transport of threonine and its utilization in the normal and growth-restricted fetus. Am J Physiol, 272:E892-E900.

Barash H, Silanikove N, Shamay A, Ezra E. 2001. Interrelationships among ambient temperature, day length, and milk yield in dairy cows under a Mediterranean climate. J Dairy Sci, 84:2314-2320.

Barry JS, Davidsen ML, Limesand SW, Galan HL, Friedman JE, Regnault TR, Hay WW Jr. 2006. Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction. Exp Biol Med (Maywood), 231:566-575.

Barry JS, Rozance PJ, Anthony RV. 2008. An animal model of placental insufficiency-induced intrauterine growth restriction. Semin Perinatol, 32:225-230.

Barry JS, Rozance PJ, Brown LD, Anthony RV, Thornburg KL, Hay WW Jr. 2016. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction. Exp Biol Med (Maywood), 241:839-847.

Bartelds B, Gratama JW, Knoester H, Takens J, Smid GB, Aarnoudse JG, Heymans HS, Kuipers JR. 1998. Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs. Am J Physiol, 4(6, pt. 2):H1962-1969.

Bartelds B, Knoester H, Smid GB, Takens J, Visser GH, Penninga L, van der Leij FR, Beaufort-Krol GC, Zijlstra WG, Heymans HS, Kuipers JR. 2000. Perinatal changes in myocardial metabolism in lambs. Circulation, 102:926-931.

Battaglia FC, Meschia G. 1978. Principal substrates of fetal metabolism. Physiol Rev, 58:499-527.

Bell AW, Wilkening RB, Meschia G. 1987. Some aspects of placental function in chronically heat-stressed ewes. J Dev Physiol, 9:17-29.

Boehmer BH, Limesand SW, Rozance PJ. 2017. The impact of IUGR on pancreatic islet development and beta-cell function. J Endocrinol, 235:R63-R76.

Brown LD, Rozance PJ, Thorn SR, Friedman JE, Hay WW Jr. 2012. Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep. Am J Physiol Endocrinol Metab, 303:E352-64.

Brown LD. 2014. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health. J. Endocrinol, 221:R13-R29.

Brown LD, Rozance PJ, Bruce JL, Friedman JE, Hay WW Jr, Wesolowski SR. 2015. Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol, 309:R920-R928.

Brown LD, Davis M, Wai S, Wesolowski SR, Hay WW Jr, Limesand SW, Rozance PJ. 2016. Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep. Endocrinology, 157:3788-3799.

Brown LD, Kohn, JR, Rozance PJ, Hay WW Jr, Wesolowski SR. 2017. Exogenous amino acids suppress glucose oxidation and potentiate hepatic glucose production in late gestation fetal sheep. Am J Physiol Regul Integr Comp Physiol, 312:R654-R663.

Camacho LE, Chen X, Hay WW Jr, Limesand SW. 2017. Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol, 313:R101-R109.

Chen X, Fahy AL, Green AS, Anderson MJ, Rhoads RP, Limesand SW. 2010. beta2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction. J Physiol, 588:3539-3549.

Chen X, Green AS, Macko AR, Yates DT, Kelly AC, Limesand SW. 2014. Enhanced insulin secretion responsiveness and islet adrenergic desensitization after chronic norepinephrine suppression is discontinued in fetal sheep. Am J Physiol Endocrinol Metab, 306:E58-E64.

Chen X, Kelly AC, Yates DT, Macko AR, Lynch RM, Limesand SW. 2017. Islet adaptations in fetal sheep persist following chronic exposure to high norepinephrine. J Endocrinol, 232:285-295.

Collier RJ, Dahl GE, VanBaale MJ. 2006. Major advances associated with environmental effects on dairy cattle. J Dairy Sci, 89:1244-1253.

Danielson L, McMillen IC, Dyer JL, Morrison JL. 2005. Restriction of placental growth results in greater hypotensive response to alpha-adrenergic blockade in fetal sheep during late gestation. J Physiol, 563:611-620.

Davis MA, Macko AR, Steyn LV, Anderson MJ, Limesand SW. 2015. Fetal adrenal demedullation lowers circulating norepinephrine and attenuates growth restriction but not reduction of endocrine cell mass in an ovine model of intrauterine growth restriction. Nutrients, 7:500-516.

de Vrijer B, Regnault TR, Wilkening RB, Meschia G, Battaglia FC. 2004. Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction. Am J Physiol Endocrinol Metab, 287:E1114-1124

de Vrijer B, Davidsen ML, Wilkening RB, Anthony RV, Regnault TR. 2006. Altered placental and fetal expression of IGFs and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy. Pediatr Res, 60:507-512.

do Amaral BC, Connor EE, Tao S, Hayen MJ, Bubolz JW, Dahl GE. 2011. Heat stress abatement during the dry period influences metabolic gene expression and improves immune status in the transition period of dairy cows. J Dairy Sci, 94:86-96.

Dunlop K, Cedrone M, Staples JF, Regnault TR. 2015. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity. Nutrients, 7:1202-1216.

Edwards LJ, Simonetta G, Owens JA, Robinson JS, McMillen IC. 1999. Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril. J Physiol, 515:897-904.

Galan HL, Hussey MJ, Barbera A, Ferrazzi E, Chung M, Hobbins JC, Battaglia FC. 1999. Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency. Am J Obstet Gynecol, 180:1278-1282.

Galan HL, Anthony RV, Rigano S, Parker TA, de Vrijer B, Ferrazzi E Wilkening RB, Regnault TR. 2005. Fetal hypertension and abnormal Doppler velocimetry in an ovine model of intrauterine growth restriction. Am J Obstet Gynecol, 192:272-279.

Gatford KL, De Blasio MJ, Thavaneswaran P, Robinson JS, McMillen IC, Owens JA. 2004. Postnatal ontogeny of glucose homeostasis and insulin action in sheep. Am J Physiol Endocrinol Metab, 286:E1050-E1059.

Greenwood PL, Hunt AS, Hermanson JW, Bell AW. 1998. Effects of birth weight and postnatal nutrition on neonatal sheep: I. Body growth and composition, and some aspects of energetic efficiency. J Anim Sci, 76:2354-2367.

Greenwood PL, Hunt AS, Hermanson JW, Bell AW. 2000. Effects of birth weight and postnatal nutrition on neonatal sheep: II. Skeletal muscle growth and development. J Anim Sci, 78:50-61.

Hagen AS, Orbus RJ, Wilkening RB, Regnault TR, Anthony RV. 2005. Placental expression of angiopoietin-1, angiopoietin-2 and tie-2 during placental development in an ovine model of placental insufficiency-fetal growth restriction. Pediatr Res, 58:1228-1232.

Hansen PJ, Drost M, Rivera RM, Paula-Lopes FF, al-Katanani YM, Krininger CE, 3rd Chase CC Jr. 2001. Adverse impact of heat stress on embryo production: causes and strategies for mitigation. Theriogenology, 55:91-103.

Hay WW Jr, Brown LD, Rozance PJ, Wesolowski SR, Limesand SW. 2016. Challenges in Nourishing the IUGR fetus-lessons learned from studies in the IUGR fetal sheep. Acta Paediatr, 105:881-889.

Jackson BT, Piasecki GJ, Cohn HE, Cohen WR. 2000. Control of fetal insulin secretion. Am J Physiol Regul Integr Comp Physiol, 279:R2179-R2188.

Kelly AC, Bidwell CA, McCarthy FM, Taska DJ, Anderson MJ, Camacho LE, Limesand SW. 2017. RNA Sequencing exposes adaptive and immune responses to intrauterine growth restriction in fetal sheep islets. Endocrinology, 158:743-755.

Kelly AC, Camacho LE, Pendarvis K, Davenport HM, Steffens NR, Smith KE, Weber CS, Lynch RM, Papas KK, Limesand SW. 2018. Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells. Mol Cell Endocrinol. doi: 10.1016/j.mce.2018.01.012.

Laporta J, Fabris TF, Skibiel AL, Powell JL, Hayen MJ, Horvath K, Miller-Cushon EK, Dahl GE. 2017. In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves. J Dairy Sci, 100:2976-2984.

Leos RA, Anderson MJ, Chen X, Pugmire J, Anderson KA, Limesand SW. 2010. Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab, 298:E770-E778.

Limesand SW, Regnault TR, Hay WW Jr. 2004. Characterization of glucose transporter 8 (GLUT8) in the ovine placenta of normal and growth restricted fetuses. Placenta 25, 70-77.

Limesand SW, Jensen J, Hutton JC, Hay WW Jr. 2005. Diminished b-cell replication contributes to reduced b-cell mass in fetal sheep with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol, 288, R1297-R1305.

Limesand SW, Rozance PJ, Zerbe GO, Hutton JC, Hay WW Jr. 2006. Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology, 147:1488-1497.

Limesand SW, Rozance PJ, Smith, D, Hay WW Jr. 2007. Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab, 293:E1716-E1725.

Limesand SW, Rozance PJ, Macko AR, Anderson MJ, Kelly AC, Hay WW Jr. 2013. Reductions in insulin concentrations and beta-cell mass precede growth restriction in sheep fetuses with placental insufficiency. Am J Physiol Endocrinol Metab, 304:E516-E523.

Limesand SW, Rozance PJ. 2017. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. J Physiol 595, 5103-5113.

Macko AR, Yates DT, Chen X, Green AS, Kelly AC, Brown LD, Limesand SW. 2013. Elevated plasma norepinephrine inhibits insulin secretion, but adrenergic blockade reveals enhanced b-cell responsiveness in an ovine model of placental insufficiency at 0.7 of gestation. J Dev Orig Health Dis, 4:402-410.

Macko AR, Yates DT, Chen X, Shelton LA, Kelly AC, Davis MA, Camacho LE, Anderson MJ, Limesand SW. 2016. Adrenal demedullation and oxygen supplementation independently increase glucose- stimulated insulin concentrations in fetal sheep with intrauterine growth restriction. Endocrinology, 157:2104-2115.

Maier A, McEwan JC, Dodds KG, Fischman DA, Fitzsimons RB, Harris AJ. 1992. Myosin heavy chain composition of single fibres and their origins and distribution in developing fascicles of sheep tibialis cranialis muscles. J Muscle Res Cell Motil, 13:551-572.

McCrabb GJ, McDonald BJ, Hennoste LM. 1993. Lamb birthweight in sheep differently acclimatized to a hot environment. Aust J Agric Res, 44:933-943.

McMillen IC, Adams MB, Ross JT, Coulter CL, Simonetta G, Owens JA, Robinson JS, Edwards LJ. 2001. Fetal growth restriction: adaptations and consequences. Reproduction, 122:195-204.

Meschia G, Cotter JR, Breathnach CS, Barron DH. 1965. The diffusibility of oxygen across the sheep placenta. Q J Exp Physiol Cogn Med Sci, 50:466-480.

Monteiro APA, Tao S, Thompson IMT, Dahl GE. 2016. In utero heat stress decreases calf survival and performance through the first lactation. J Dairy Sci, 99:8443-8450.

Pavlath GK, Rich K, Webster SG, Blau HM. 1989. Localization of muscle gene products in nuclear domains. Nature, 337:570-573.

Regnault TR, Galan HL, Parker TA, Anthony RV. 2002a. Placental development in normal and compromised pregnancies. Placenta, 23(suppl. A):S119-S129.

Regnault TR, Orbus RJ, de Vrijer B, Davidsen ML, Galan HL, Wilkening RB, Anthony RV. 2002b. Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta, 23:132-144.

Regnault TR, de Vrijer B, Galan HL, Davidsen ML, Trembler KA, Battaglia FC, Wilkening RB, Anthony RV. 2003. The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction. J Physiol, 550:641-656.

Regnault TR, Friedman JE, Wilkening RB, Anthony RV, Hay WW Jr. 2005. Fetoplacental transport and utilization of amino acids in IUGR--a review. Placenta, 26(suppl. A):S52-62.

Regnault TR, de Vrijer B, Galan HL, Wilkening RB, Battaglia FC, Meschia G. 2007. Development and mechanisms of fetal hypoxia in severe fetal growth restriction. Placenta, 28:714-723.

Regnault TR, de Vrijer B, Galan HL, Wilkening RB, Battaglia FC, Meschia G. 2013. Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction. Pediatr Res, 73:602-611.

Reynolds LP, Ferrell CL, Nienaber JA, Ford SP. 1985. Effects of chronic enviromental heat stress on blood flow and nutrient uptake of the gravid bovine uterus and foetus. J Agric Sci, 104:289-297.

Ross JC, Fennessey PV, Wilkening RB, Battaglia FC, Meschia G. 1996. Placental transport and fetal utilization of leucine in a model of fetal growth retardation. Am J Physiol, 270:E491-E503.

Rozance PJ, Zastoupil L, Wesolowski SR, Goldstrohm DA, Strahan B, Cree-Green M, Sheffield-Moore M, Meschia G, Hay WW Jr, Wilkening RB, Brown LD. 2018. Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep. J Physiol, 596:67-82.

Shelton M. 1964. Relation of birth weight to death losses and to certain productive characters of fall-born lambs. J Anim Sci, 23:355-359.

Thorn SR, Regnault TR, Brown LD, Rozance PJ, Keng J, Roper M, Wilkening RB, Hay WW Jr, Friedman JE. 2009. Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle. Endocrinology, 150:3021-3030.

Thorn SR, Brown LD, Rozance PJ, Hay WW Jr, Friedman JE. 2013. Increased hepatic glucose production in fetal sheep with intrauterine growth restriction is not suppressed by insulin. Diabetes, 62:65-73.

Thureen PJ, Trembler KA, Meschia G, Makowski EL, Wilkening RB. 1992. Placental glucose transport in heat-induced fetal growth retardation. Am J Physiol, 263:R578-R585.

Vatnick I, Ignotz G, McBride BW, Bell AW. 1991. Effect of heat stress on ovine placental growth in early pregnancy. J Dev Physiol, 16:163-166.

Wallace JM, Regnault TR, Limesand SW, Hay WW Jr, Anthony RV. 2005. Investigating the causes of low birth weight in contrasting ovine paradigms. J Physiol, 565:19-26.

Wells JC, Cole TJ. 2002. Birth weight and environmental heat load: a between-population analysis. Am J Phys. Anthropol, 119:276-282.

West JW. 2003. Effects of heat-stress on production in dairy cattle. J Dairy Sci, 86:2131-2144.

Wilkening RB, Anderson S, Martensson L, Meschia G. 1982. Placental transfer as a function of uterine blood flow. Am J Physiol, 242:H429-H436.

Wilson SJ, McEwan JC, Sheard PW, Harris AJ. 1992. Early stages of myogenesis in a large mammal: formation of successive generations of myotubes in sheep tibialis cranialis muscle. J Muscle Res Cell Motil, 13:534-550.

Wu G, Bazer FW, Wallace JM, Spencer TE. 2006. Board-invited review: intrauterine growth retardation: implications for the animal sciences. J Anim Sci, 84:2316-2337.

Yates DT, Macko AR, Nearing M, Chen X, Rhoads RP, Limesand SW. 2012. Developmental programming in response to intrauterine growth restriction impairs myoblast function and skeletal muscle metabolism. J Pregnancy, 2012:631038. doi: 10.1155/2012/631038.

Yates DT, Clarke DS, Macko AR, Anderson MJ, Shelton LA, Nearing M, Allen RE, Rhoads RP, Limesand SW. 2014. Myoblasts from intrauterine growth-restricted sheep fetuses exhibit intrinsic deficiencies in proliferation that contribute to smaller semitendinosus myofibres. J Physiol, 592:3113-3125.

Yates DT, Cadaret CN, Beede KA, Riley HE, Macko AR, Anderson MJ, Camacho LE, Limesand SW. 2016. Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term. Am J Physiol Regul Integr Comp Physiol, 310:R1020-R1029.

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