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Maternal, Placental, and Fetal Responses to Intermittent Heat Exposure During Late Gestation in Mice

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Abstract

Physiological adaptations during heat exposure are critical in pregnancy. Maternal thermoregulation has to accommodate the increased metabolic load of the developing fetus. Here, we assess the consequences of intermittent heat exposure, as occurs in heat waves, for maternal adaptations during pregnancy, and chronic feto-placental outcomes. Following timed mating, C57BL/6J mice were allocated to either standard animal housing temperature conditions (SH) or housing at a temperature within the thermoneutral zone (TNZ). A subset of the TNZ group was exposed to 37 °C for 8 h a day from E15.5 to E17.5 to simulate a heat wave (HW). Maternal weight gain, food intake, rectal temperature, and nesting behaviors were measured across gestation. Fetal and placental tissues were collected at E18.5. With heat exposure, maternal rectal temperature increased while food intake and nest complexity decreased. Maternal daily weight gain initially decreased due to heat exposure, but on the last day of exposure, it was comparable to the other experimental groups. These maternal responses during heat exposure impacted on the fetus, with restrictions in placental and fetal development evident just before birth. Thus, the vascular portion of the placenta, and the relative fetal head size, was smaller. Furthermore, SH and TNZ animals demonstrated distinct differences in food intake and nesting behavior during pregnancy, reinforcing the need for caution in extrapolating from animal models to humans when housing occurs outside of thermoneutral zone conditions. This study highlights the direct effects of temperature conditions on health in pregnancy and provides a foundation for future studies to investigate fetal health consequences that are associated with intermittent heat exposure.

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References

  1. Watts N, Amann M, Ayeb-Karlsson S, Belesova K, Bouley T, Boykoff M, et al. The Lancet Countdown on health and climate change: from 25 years of inaction to a global transformation for public health. Lancet. 2018;391(10120):581–630. https://doi.org/10.1016/S0140-6736(17)32464-9.

    Article  PubMed  Google Scholar 

  2. Xu C, Kohler TA, Lenton TM, Svenning JC, Scheffer M. Future of the human climate niche. Proc Natl Acad Sci U S A. 2020;117:11350–5. https://doi.org/10.1073/pnas.1910114117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Steffen W, Hughes L, Perkins S. Heatwaves: hotter, longer, more often. Climate Council of Australia 2014.

  4. Schroder HJ, Power GG. Engine and radiator: fetal and placental interactions for heat dissipation. Exp Physiol. 1997;82(2):403–14.

    Article  CAS  Google Scholar 

  5. Laburn HP, Faurie A, Goelst K, Mitchell D. Effects on fetal and maternal body temperatures of exposure of pregnant ewes to heat, cold, and exercise. J Appl Physiol (1985). 2002;92(2):802–8. https://doi.org/10.1152/japplphysiol.00109.2001.

    Article  Google Scholar 

  6. Laburn HP, Mitchell D, Goelst K. Fetal and maternal body temperatures measured by radiotelemetry in near-term sheep during thermal stress. J Appl Physiol (1985). 1992;72(3):894–900. https://doi.org/10.1152/jappl.1992.72.3.894.

    Article  CAS  Google Scholar 

  7. Cil G, Cameron TA. Potential climate change health risks from increases in heat waves: abnormal birth outcomes and adverse maternal health conditions. Risk Anal. 2017;37(11):2066–79. https://doi.org/10.1111/risa.12767.

    Article  PubMed  Google Scholar 

  8. Basu R, Rau R, Pearson D, Malig B. Temperature and term low birth weight in California. Am J Epidemiol. 2018;187:2306–14. https://doi.org/10.1093/aje/kwy116.

    Article  PubMed  Google Scholar 

  9. Zheng X, Zhang W, Lu C, Norback D, Deng Q. An epidemiological assessment of the effect of ambient temperature on the incidence of preterm births: identifying windows of susceptibility during pregnancy. J Therm Biol. 2018;74:201–7. https://doi.org/10.1016/j.jtherbio.2018.04.001.

    Article  PubMed  Google Scholar 

  10. Kuehn L, McCormick S. Heat exposure and maternal health in the face of climate change. Int J Environ Res Public Health. 2017;14(8). doi:https://doi.org/10.3390/ijerph14080853.

  11. Wang J, Williams G, Guo Y, Pan X, Tong S. Maternal exposure to heatwave and preterm birth in Brisbane, Australia. BJOG. 2013;120(13):1631–41. https://doi.org/10.1111/1471-0528.12397.

    Article  CAS  PubMed  Google Scholar 

  12. Beltran AJ, Wu J, Laurent O. Associations of meteorology with adverse pregnancy outcomes: a systematic review of preeclampsia, preterm birth and birth weight. Int J Environ Res Public Health. 2013;11(1):91–172. https://doi.org/10.3390/ijerph110100091.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vicedo-Cabrera AM, Iniguez C, Barona C, Ballester F. Exposure to elevated temperatures and risk of preterm birth in Valencia, Spain. Environ Res. 2014;134:210–7. https://doi.org/10.1016/j.envres.2014.07.021.

    Article  CAS  PubMed  Google Scholar 

  14. Hansen PJ. Effects of heat stress on mammalian reproduction. Philos Trans R Soc Lond Ser B Biol Sci. 2009;364(1534):3341–50. https://doi.org/10.1098/rstb.2009.0131.

    Article  Google Scholar 

  15. Koyama H, Ikeda S, Sugimoto M, Kume S. Effects of folic acid on the development and oxidative stress of mouse embryos exposed to heat stress. Reprod Domest Anim. 2012;47(6):921–7. https://doi.org/10.1111/j.1439-0531.2012.01992.x.

    Article  CAS  PubMed  Google Scholar 

  16. Ziskin MC, Morrissey J. Thermal thresholds for teratogenicity, reproduction, and development. Int J Hyperth. 2011;27(4):374–87. https://doi.org/10.3109/02656736.2011.553769.

    Article  Google Scholar 

  17. Thureen PJ, Trembler KA, Meschia G, Makowski EL, Wilkening RB. Placental glucose transport in heat-induced fetal growth retardation. Am J Phys. 1992;263(3 Pt 2):R578–85. https://doi.org/10.1152/ajpregu.1992.263.3.R578.

    Article  CAS  Google Scholar 

  18. Dreiling CE, Carman FS 3rd, Brown DE. Maternal endocrine and fetal metabolic responses to heat stress. J Dairy Sci. 1991;74(1):312–27. https://doi.org/10.3168/jds.S0022-0302(91)78175-7.

    Article  CAS  PubMed  Google Scholar 

  19. Regnault TR, Orbus RJ, de Vrijer B, Davidsen ML, Galan HL, Wilkening RB, et al. Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta. 2002;23(2–3):132–44. https://doi.org/10.1053/plac.2001.0757.

    Article  CAS  PubMed  Google Scholar 

  20. Fischer AW, Cannon B, Nedergaard J. Optimal housing temperatures for mice to mimic the thermal environment of humans: an experimental study. Mol Metab. 2018;7:161–70. https://doi.org/10.1016/j.molmet.2017.10.009.

    Article  CAS  PubMed  Google Scholar 

  21. Ganeshan K, Chawla A. Warming the mouse to model human diseases. Nat Rev Endocrinol. 2017;13(8):458–65. https://doi.org/10.1038/nrendo.2017.48.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Maloney SK, Fuller A, Mitchell D, Gordon C, Overton JM. Translating animal model research: does it matter that our rodents are cold? Physiology (Bethesda). 2014;29(6):413–20. https://doi.org/10.1152/physiol.00029.2014.

    Article  CAS  Google Scholar 

  23. Hess SE, Rohr S, Dufour BD, Gaskill BN, Pajor EA, Garner JP. Home improvement: C57BL/6J mice given more naturalistic nesting materials build better nests. J Am Assoc Lab Anim Sci. 2008;47(6):25–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Clarke MW, Tuckey RC, Gorman S, Holt B, Hart PH. Optimized 25-hydroxyvitamin D analysis using liquid–liquid extraction with 2D separation with LC/MS/MS detection, provides superior precision compared to conventional assays. Metabolomics. 2013;9(5):1031–40. https://doi.org/10.1007/s11306-013-0518-9.

    Article  CAS  Google Scholar 

  25. Wharfe MD, Mark PJ, Wyrwoll CS, Smith JT, Yap C, Clarke MW, et al. Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids. J Endocrinol. 2016;228(3):135–47. https://doi.org/10.1530/JOE-15-0405.

    Article  CAS  PubMed  Google Scholar 

  26. Tesic D, Hawes JE, Zosky GR, Wyrwoll CS. Vitamin D deficiency in BALB/c mouse pregnancy increases placental transfer of glucocorticoids. Endocrinology. 2015;156(10):3673–9. https://doi.org/10.1210/en.2015-1377.

    Article  CAS  PubMed  Google Scholar 

  27. Roberts CT, White CA, Wiemer NG, Ramsay A, Robertson SA. Altered placental development in interleukin-10 null mutant mice. Placenta. 2003;24 Suppl A:S94–9.

  28. Groves NJ, Kesby JP, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH. Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice. Behav Brain Res. 2013;241:120–31. https://doi.org/10.1016/j.bbr.2012.12.001.

    Article  CAS  PubMed  Google Scholar 

  29. Fewell JE. Body temperature regulation in rats near term of pregnancy. Can J Physiol Pharmacol. 1995;73(3):364–8.

    Article  CAS  Google Scholar 

  30. Wharfe MD, Wyrwoll CS, Waddell BJ, Mark PJ. Pregnancy suppresses the daily rhythmicity of core body temperature and adipose metabolic gene expression in the mouse. Endocrinology. 2016;157(9):3320–31. https://doi.org/10.1210/en.2016-1177.

    Article  CAS  PubMed  Google Scholar 

  31. Crew RC, Waddell BJ, Maloney SK, Mark PJ. Diet-induced obesity reduces core body temperature across the estrous cycle and pregnancy in the rat. Chronobiol Int. 2018;35(8):1077–87. https://doi.org/10.1080/07420528.2018.1458035.

    Article  PubMed  Google Scholar 

  32. Gaskill BN, Gordon CJ, Pajor EA, Lucas JR, Davis JK, Garner JP. Impact of nesting material on mouse body temperature and physiology. Physiol Behav. 2013;110–111:87–95. doi:https://doi.org/10.1016/j.physbeh.2012.12.018.

  33. Nagashima K, Nakai S, Konishi M, Su L, Kanosue K. Increased heat-escape/cold-seeking behavior following hypertonic saline injection in rats. Am J Phys Regul Integr Comp Phys. 2001;280(4):R1031–6. https://doi.org/10.1152/ajpregu.2001.280.4.R1031.

    Article  CAS  Google Scholar 

  34. Westerterp KR. Diet induced thermogenesis. Nutr Metab (Lond). 2004;1(1):5. https://doi.org/10.1186/1743-7075-1-5.

    Article  CAS  Google Scholar 

  35. Gordon CJ. The mouse thermoregulatory system: its impact on translating biomedical data to humans. Physiol Behav. 2017;179:55–66. https://doi.org/10.1016/j.physbeh.2017.05.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Coan PM, Ferguson-Smith AC, Burton GJ. Developmental dynamics of the definitive mouse placenta assessed by stereology. Biol Reprod. 2004;70(6):1806–13.

    Article  CAS  Google Scholar 

  37. Wyrwoll CS, Seckl JR, Holmes MC. Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology. 2009;150(3):1287–93. https://doi.org/10.1210/en.2008-1100.

    Article  CAS  PubMed  Google Scholar 

  38. Yamauchi C, Fujita S, Obara T, Ueda T. Effects of room temperature on reproduction, body and organ weights, food and water intakes, and hematology in mice. Jikken Dobutsu. 1983;32(1):1–11.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors give many thanks to the staff in the Cell Central and Animal Care Services at the School of Human Sciences, University of Western Australia, for their assistance with this project.

Funding

The study was funded by a Raine BrightSpark grant awarded to GP, CW, and SM.

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Correspondence to Caitlin S. Wyrwoll.

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The Animal Ethics Committee of the University of Western Australia approved all procedures associated with this study (RA/3/100/1509).

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Olivier, K., Reinders, L.A., Clarke, M.W. et al. Maternal, Placental, and Fetal Responses to Intermittent Heat Exposure During Late Gestation in Mice. Reprod. Sci. 28, 416–425 (2021). https://doi.org/10.1007/s43032-020-00291-7

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  • DOI: https://doi.org/10.1007/s43032-020-00291-7

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