Evaluating the Impact of Heat Stress on Placental Function: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Eligibility Criteria
2.2. Information Sources and Search Strategy
2.3. Study Selection Process
2.4. Extraction and Synthesis
2.5. Assessment of Quality of Evidence
3. Results
3.1. Literature Search
3.2. Study Characteristics
3.3. Findings of Heat Effects on the Placenta
3.3.1. Weight and Efficiency
3.3.2. Uteroplacental Blood Flow
3.3.3. Placental Anatomy
3.3.4. Gene Expression
3.3.5. Placental Steroids
4. Discussion
4.1. Literature Search and Study Characteristics
4.2. Study Methodology and Design Implications to Heat and Placenta Studies with Human Subjects
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Jones, B.; O’Neill, B.C.; McDaniel, L.; McGinnis, S.; Mearns, L.O.; Tebaldi, C. Future population exposure to US heat extremes. Nat. Clim. Chang. 2015, 5, 652–655. [Google Scholar] [CrossRef]
- NOAA National Centers for Enviornmental Information. Monthly Global Climate Report for Annual 2022. 2023. Available online: https://www.ncei.noaa.gov/access/monitoring/monthly-report/global/202213 (accessed on 26 July 2023).
- IPCC Intergovernmental Panel on Climate Change. Climate Change 2021: The Physical Science Basis; IPOC Change: Geneva, Switzerland, 2021. [Google Scholar]
- Im, E.S.; Pal, J.S.; Eltahir, E.A.B. Deadly heat waves projected in the densely populated agricultural regions of South Asia. Sci. Adv. 2017, 3, e1603322. [Google Scholar] [CrossRef]
- Pal, J.S.; Eltahir, E.A.B. Future temperature in southwest Asia projected to exceed a threshold for human adaptability. Nat. Clim. Chang. 2016, 6, 197–200. [Google Scholar] [CrossRef]
- Raymond, C.; Matthews, T.; Horton, R.M. The emergence of heat and humidity too severe for human tolerance. Sci. Adv. 2020, 6, eaaw1838. [Google Scholar] [CrossRef]
- Russo, S.; Sillmann, J.; Sterl, A. Humid heat waves at different warming levels. Sci. Rep. 2017, 7, 7477. [Google Scholar] [CrossRef]
- Levy, B.S.; Patz, J.A. Climate Change, Human Rights, and Social Justice. Clim. Chang. Glob. Health Hum. Rights 2015, 81, 310–322. [Google Scholar] [CrossRef] [PubMed]
- Hondula, D.M.; Davis, R.E.; Saha, M.V.; Wegner, C.R.; Veazey, L.M. Geographic dimensions of heat-related mortality in seven U.S. cities. Environ. Res. 2015, 138, 439–452. [Google Scholar] [CrossRef] [PubMed]
- Ebi, K.L.; Capon, A.; Berry, P.; Ebi, K.L.; Capon, A.; Berry, P.; Broderick, C.; de Dear, R.; Havenith, G.; Honda, Y.; et al. Hot weather and heat extremes: Health risks. Lancet Lond Engl. 2021, 398, 698–708. [Google Scholar] [CrossRef] [PubMed]
- Thompson, R.; Hornigold, R.; Page, L.; Waite, T. Associations between high ambient temperatures and heat waves with mental health outcomes: A systematic review. Public Health 2018, 161, 171–191. [Google Scholar] [CrossRef]
- Kuehn, L.; McCormick, S. Heat Exposure and Maternal Health in the Face of Climate Change. Int. J. Environ. Res. Public Health 2017, 14, 853. [Google Scholar] [CrossRef]
- Samuels, L.; Nakstad, B.; Roos, N.; Bonell, A.; Chersich, M.; Havenith, G.; Luchters, S.; Day, L.T.; Hirst, J.E.; Singh, T.; et al. Physiological mechanisms of the impact of heat during pregnancy and the clinical implications: Review of the evidence from an expert group meeting. Int. J. Biometeorol. 2022, 66, 1505–1513. [Google Scholar] [CrossRef] [PubMed]
- Syed, S.; O’Sullivan, T.L.; Phillips, K.P. Extreme Heat and Pregnancy Outcomes: A Scoping Review of the Epidemiological Evidence. Int. J. Environ. Res. Public Health 2022, 19, 2412. [Google Scholar] [CrossRef] [PubMed]
- Wells, J.C.K. Thermal Environment and Human Birth Weight. J. Theor. Biol. 2002, 214, 413–425. [Google Scholar] [CrossRef]
- Sun, S.; Weinberger, K.R.; Spangler, K.R.; Eliot, M.N.; Braun, J.M.; Wellenius, G.A. Ambient temperature and preterm birth: A retrospective study of 32 million US singleton births. Environ. Int. 2019, 126, 7–13. [Google Scholar] [CrossRef] [PubMed]
- Chersich, M.F.; Pham, M.D.; Areal, A.; Haghighi, M.M.; Manyuchi, A.; Swift, C.P.; Wernecke, B.; Robinson, M.; Hetem, R.; Boeckmann, M.; et al. Associations between high temperatures in pregnancy and risk of preterm birth, low birth weight, and stillbirths: Systematic review and meta-analysis. BMJ 2020, 371, m3811. [Google Scholar] [CrossRef]
- Rampersad, R.; Cervar-Zivkovic, M.; Nelson, D.M. Immunologic Aspects of Pregnancy. In The Placenta: From Development to Disease; Wiley-Blackwell: Hoboken, NJ, USA, 2011; p. 29. [Google Scholar]
- Huppertz, B. Vascular Development in the Placenta. In The Placenta: From Development to Disease; Wiley-Blackwell: Hoboken, NJ, USA, 2011; p. 40. [Google Scholar]
- Thureen, P.J.; Trembler, K.A.; Meschia, G.; Makowski, E.L.; Wilkening, R.B. Placental glucose transport in heat-induced fetal growth retardation. Am. J. Physiol-Regul. Integr. Comp. Physiol. 1992, 263, R578–R585. [Google Scholar] [CrossRef]
- Regnault, T.R.; de Vrijer, B.; Galan, H.L.; Wilkening, R.B.; Battaglia, F.C.; Meschia, G. Development and Mechanisms of Fetal Hypoxia in Severe Fetal Growth Restriction. Placenta 2007, 28, 714–723. [Google Scholar] [CrossRef]
- Bonell, A.; Sonko, B.; Badjie, J.; Samateh, T.; Saidy, T.; Sosseh, F.; Sallah, Y.; Bajo, K.; Murray, K.A.; Hirst, J.; et al. Environmental heat stress on maternal physiology and fetal blood flow in pregnant subsistence farmers in The Gambia, west Africa: An observational cohort study. Lancet Planet Health 2022, 6, e968–e976. [Google Scholar] [CrossRef]
- Krishna, U.; Bhalerao, S. Placental insufficiency and fetal growth restriction. J. Obstet. Gynaecol. India 2011, 61, 505–511. [Google Scholar] [CrossRef]
- Cowell, W.; Ard, N.; Herrera, T.; Medley, E.A.; Trasande, L. Ambient temperature, heat stress and fetal growth: A review of placenta-mediated mechanisms. Mol. Cell Endocrinol. 2023, 576, 112000. [Google Scholar] [CrossRef] [PubMed]
- Beltran, A.J.; 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, 91–172. [Google Scholar] [CrossRef]
- Bekkar, B.; Pacheco, S.; Basu, R.; DeNicola, N. Association of Air Pollution and Heat Exposure With Preterm Birth, Low Birth Weight, and Stillbirth in the US: A Systematic Review. JAMA Netw. Open 2020, 3, e208243. [Google Scholar] [CrossRef]
- Strand, L.B.; Barnett, A.G.; Tong, S. The influence of season and ambient temperature on birth outcomes: A review of the epidemiological literature. Environ. Res. 2011, 111, 451–462. [Google Scholar] [CrossRef] [PubMed]
- Dilworth, M.R.; Sibley, C.P. Review: Transport across the placenta of mice and women. Placenta 2013, 34, S34–S39. [Google Scholar] [CrossRef] [PubMed]
- Buse, E.; Markert, U.R. The immunology of the macaque placenta: A detailed analysis and critical comparison with the human placenta. Crit. Rev. Clin. Lab. Sci. 2019, 56, 118–145. [Google Scholar] [CrossRef]
- Ma, Y.; Hu, Y.; Ma, J. Animal models of the placenta accreta spectrum: Current status and further perspectives. Front. Endocrinol. 2023, 14, 1118168. [Google Scholar] [CrossRef] [PubMed]
- Tricco, A.C.; Lillie, E.; Zarin, W.; O‘brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.; Horsley, T.; Weeks, L.; et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018, 169, 467–473. [Google Scholar] [CrossRef] [PubMed]
- Covidence Systematic Review Software, Veritas Health Innovation, Melbourne, Australia. Available online: www.covidence.org (accessed on 26 July 2023).
- Andrianakis, P.; Walker, D. Effect of hyperthermia on uterine and umbilical blood flows in pregnant sheep. Exp. Physiol. 1994, 79, 1–13. [Google Scholar] [CrossRef]
- Nakamura, H.; Nagase, H.; Ogino, K.; Hatta, K.; Matsuzaki, I. Heat Produces Uteroplacental Circulatory Disturbance in Pregnant Rats through Action of Corticotropin Releasing Hormone (CRH). Placenta 2000, 21, 510–515. [Google Scholar] [CrossRef]
- Vähä-Eskeli, K.; Erkkola, R.; Irjala, K.; Uotila, P.; Poranen, A.K.; Säteri, U. Responses of placental steroids, prostacyclin and thromboxane A2 to thermal stress during pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 1992, 43, 97–103. [Google Scholar] [CrossRef]
- Guo, H.; Yang, Y.; Qiao, Y.; He, J.; Yao, W.; Zheng, W. Heat stress affects fetal brain and intestinal function associated with the alterations of placental barrier in late pregnant mouse. Ecotoxicol. Environ. Saf. 2021, 227, 112916. [Google Scholar] [CrossRef] [PubMed]
- Guo, H.; Liu, R.; He, J.; Yao, W.; Zheng, W. Heat Stress Modulates a Placental Immune Response Associated with Alterations in the Development of the Fetal Intestine and Its Innate Immune System in Late Pregnant Mouse. Front. Physiol. 2022, 13, 841149. [Google Scholar] [CrossRef] [PubMed]
- Dreiling, C.E.; Carman, F.S.; Brown, D.E. Maternal Endocrine and Fetal Metabolic Responses to Heat Stress. J. Dairy Sci. 1991, 74, 312–327. [Google Scholar] [CrossRef] [PubMed]
- Arora, K.L.; Cohen, B.J.; Beaudoin, A.R. Fetal and placental responses to artificially induced hyperthermia in rats. Teratology 1979, 19, 251–259. [Google Scholar] [CrossRef]
- Bell, A.W.; Wilkening, R.B.; Meschia, G. Some aspects of placental function in chronically heat-stressed ewes. J. Dev. Physiol. 1987, 9, 17–29. [Google Scholar]
- Dada, J.M.; Santos, M.L.; Dani, A.P.; Dammann, C.P.; Pinto, L.; Vieira, F.M.; Barros, F.R. Placental Development and Physiological Changes in Pregnant Ewes in Silvopastoral and Open Pasture Systems during the Summer. Animals 2023, 13, 478. [Google Scholar] [CrossRef]
- Early, R.J.; McBride, B.W.; Vatnick, I.; Bell, A.W. Chronic heat stress and prenatal development in sheep: II. Placental cellularity and metabolism. J. Anim. Sci. 1991, 69, 3610–3616. [Google Scholar] [CrossRef] [PubMed]
- El-Sherbiny, H.R.; Samir, H.; El-Shalofy, A.S.; Abdelnaby, E.A. Exogenous L-arginine administration improves uterine vascular perfusion, uteroplacental thickness, steroid concentrations and nitric oxide levels in pregnant buffaloes under subtropical conditions. Reprod. Domest. Anim. 2022, 57, 1493–1504. [Google Scholar] [CrossRef]
- Galan, H.L.; Hussey, M.J.; Barbera, A.; Ferrazzi, E.; Chung, M.; Hobbins, J.C.; Battaglia, F.C. Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency. Am. J. Obstet. Gynecol. 1999, 180, 1278–1282. [Google Scholar] [CrossRef] [PubMed]
- Galan, H.L.; Hussey, M.J.; Chung, M.; Chyu, J.K.; Hobbins, J.C.; Battaglia, F.C. Doppler velocimetry of growth-restricted fetuses in an ovine model of placental insufficiency. Am. J. Obstet. Gynecol. 1998, 178, 451–456. [Google Scholar] [CrossRef]
- Hensleigh, P.A.; Johnson, D.C. Heat Stress Effects During Pregnancy. I. Retardation of Fetal Rat Growth*. Fertil. Steril. 1971, 22, 522–527. [Google Scholar] [CrossRef]
- Nanas, I.; Barbagianni, M.; Dadouli, K.; Dovolou, E.; Amiridis, G.S. Ultrasonographic findings of the corpus luteum and the gravid uterus during heat stress in dairy cattle. Reprod. Domest. Anim. 2021, 56, 1329–1341. [Google Scholar] [CrossRef] [PubMed]
- Olivier, K.; Reinders, L.A.; Clarke, M.W.; Crew, R.C.; Pereira, G.; Maloney, S.K.; Wyrwoll, C.S. Maternal, Placental, and Fetal Responses to Intermittent Heat Exposure During Late Gestation in Mice. Reprod Sci. 2021, 28, 416–425. [Google Scholar] [CrossRef] [PubMed]
- Padmanabhan, R.; Al-Menhali, N.M.; Ahmed, I.; Kataya, H.H.; Ayoub, M.A. Histological, histochemical and electron microscopic changes of the placenta induced by maternal exposure to hyperthermia in the rat. Int. J. Hyperth. 2005, 21, 29–44. [Google Scholar] [CrossRef] [PubMed]
- Regnault, T.R.; Orbus, R.J.; Battaglia, F.C.; Wilkening, R.B.; Anthony, R.V. Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency. J. Endocrinol. 1999, 162, 433–442. [Google Scholar] [CrossRef]
- Silva, P.D.; Hooper, H.B.; Manica, E.; Merighe, G.K.; Oliveira, S.A.; Traldi, A.D.; Negrão, J.A. Heat stress affects the expression of key genes in the placenta, placental characteristics, and efficiency of Saanen goats and the survival and growth of their kids. J. Dairy Sci. 2021, 104, 4970–4979. [Google Scholar] [CrossRef]
- Vähä-Eskeli, K.K.; Erkkola, R.U.; Seppänen, A.; Poranen, A.K.; Säteri, U. Haemodynamic response to moderate thermal stress in pregnancy. Ann. Med. 1991, 23, 121–126. [Google Scholar] [CrossRef]
- Vatnick, I.; Ignotz, G.; McBride, B.W.; Bell, A.W. Effect of heat stress on ovine placental growth in early pregnancy. J. Dev. Physiol. 1991, 16, 163–166. [Google Scholar]
- Walker, D.W.; Hale, J.R.; Fawcett, A.A.; Pratt, N.M. Cardiovascular responses to heat stress in late gestation fetal sheep. Exp. Physiol. 1995, 80, 755–766. [Google Scholar] [CrossRef] [PubMed]
- Zhao, W.; Artaiz, O.; Iqbal, Y.; Le, H.H.; DiGiacomo, K.; Leury, B.J.; Fothergill, L.J.; Furness, J.B.; Liu, F.; Green, M.P.; et al. Heat stress of gilts around farrowing causes oxygen insufficiency in the umbilical cord and reduces piglet survival. Animal 2022, 16, 100668. [Google Scholar] [CrossRef]
- Zhao, W.; Liu, F.; Bell, A.W.; Le, H.H.; Cottrell, J.J.; Leury, B.J.; Green, M.P.; Dunshea, F.R. Controlled elevated temperatures during early-mid gestation cause placental insufficiency and implications for fetal growth in pregnant pigs. Sci. Rep. 2020, 10, 20677. [Google Scholar] [CrossRef] [PubMed]
- Zhao, W.; Liu, F.; Marth, C.D.; Green, M.P.; Le, H.H.; Leury, B.J.; Bell, A.W.; Dunshea, F.R.; Cottrell, J.J. Maternal Heat Stress Alters Expression of Genes Associated with Nutrient Transport Activity and Metabolism in Female Placentae from Mid-Gestating Pigs. Int. J. Mol. Sci. 2021, 22, 4147. [Google Scholar] [CrossRef] [PubMed]
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Authors | Total Studies Included | Methodologies Reviewed | Study Designs | Temperature Parameters | Methods for Temperature Measurements | Pregnancy Window Exposure | Pregnancy Outcome Variables |
---|---|---|---|---|---|---|---|
Beltran et al., 2014 [25] | 90 | No | N/A | Tropical versus non-tropical | Min and max daily temperatures, precipitation, relative humidity | First, second, and third trimesters Last month of pregnancy | Hypertensive disorders of pregnancy, length of gestation, birth weight |
Bekkar et al., 2020 [26] | 68 | Yes | Forty-nine cohort studies Six case-crossover Five cross-sectional Four time series Four case-control | Seasonal Monthly Weekly | Weekly mean apparent temperature, weekly mean extreme temperature | Second and third trimesters Week before delivery | Preterm birth Low birth weight Stillbirth |
Chersich et al., 2020 [17] | 70 | No | N/A | Heat wave and non-heatwave days | OR and hazard ratios of preterm birth, low birth weight, and stillbirth on heat wave days | Exposure during one trimester or all trimesters Exposure period <4 weeks | Preterm birth Birthweight Stillbirth |
Strand et al., 2011 [27] | 32 | No | N/A | Seasonal heat patterns | Mean weekly temperatures and humidity index Daily min and max | Each trimester Middle 10 days of each trimester A total of 10 days around conception Day of birth Month of birth | Preterm birth Stillbirth Low birth weight |
Syed et al., 2022 [14] | 83 | Yes | Thirty-one cohort Sixteen population registry Thirteen time registry Eleven case-crossover Seven case-control Two case series One not stated | Hourly Daily Monthly Seasonal Climate Heatwave | Temperature data obtained from regional monitoring stations | First trimester Second and third trimesters Third trimester only All/any part of the pregnancy Delivery date | Preterm birth Birthweight Congenital anomaly Stillbirth |
Author | Study Design | Population | Data Collection Timeframe | Temperature Exposure Parameters | Pregnancy Window of Assessment | Methods for Temperature Assessment | Pregnancy Outcome Variables | Significant Findings |
---|---|---|---|---|---|---|---|---|
Bonell et al., 2022 [22] | Observational cohort | n = 92 Inclusion criteria: those who were 16 years or older and at <36 weeks’ gestation and involved in agricultural or related manual daily tasks of living Exclusion criteria: those who refused to consent, had multiple pregnancies, were acutely unwell, or were diagnosed with pre-eclampsia or eclampsia | 2019–2020 | Rainy season (August–October) First half of the dry season (November–March) | Every 2 months during pregnancy until delivery | Heat stress was measured during work shifts by wet bulb globe temperature (WBGT) and by using the universal thermal climate index (UTCI). Maternal heat strain was measured by the modified physiological strain index calculated from heart rate (via ultrasound) and skin temperature | Fetal heart rate, fetal strain | Significant increase in FHR from baseline at rest (125 [SD 7.9] bpm) to the working period (147 [SD 11.9] bpm; p < 0.0001 was found. The total effect of UTCI on fetal strain resulted in an odds ratio (OR) of 1.17 (95% CI 1.09–1.29; p < 0.0001), with an adjusted direct effect of OR of 1.12 (1.03–1.21; p = 0.010). |
Sheep | Rats | Buffalo | Cows | Goats | Pigs | Human |
---|---|---|---|---|---|---|
Early: Day 1–50 | Early: Day 1–7 | Early: Day 1–100 | Early: Day 1–95 | Early: Day 1–50 | Early: Day 1–38 | Early: conception to 12 weeks |
Mid: Day 51–100 | Mid: Day 8–15 | Mid: Day 101–200 | Mid: Day 96–191 | Mid: Day 51–100 | Mid: Day 39–77 | Mid: 13–27 weeks |
Late: Day 101–150± | Late: Day 16–23± | Late: Day 201–300± | Late: Day 192–285± | Late: Day 101–150± | Late: Day 78–115± | Late: 28–40 weeks ± |
Total average Gestation in Days: 150–153 | Total average Gestation in Days: 21–24 | Total average Gestation in Days: 305–320 | Total average Gestation in Days: 279–289 | Total average Gestation in Days: 145–155 | Total average Gestation in Days: 115 | Total average Gestation in Weeks: about 40 weeks |
Authors/Title/Country/ RCT or NON-RCT | Population | Pregnancy Window of Exposure | Temperature Exposure Parameters | Placental Outcome Variables | Major Results | Risk of Bias (Rated by Two Independent Reviewers) |
---|---|---|---|---|---|---|
Andrianakis and Walker, 1994 [33] Effect of Hyperthermia on Uterine and Umbilical Blood Flows in Pregnant Sheep Australia NON-RCT | Nine pregnant Border Leicester-Merino cross-bred sheep. | Total of 125–142 days (late) gestation. | Three radiant fan heaters were used to expose subjects to 43 °C for 8 h. The normal air-conditioned temperature was 21 °C with 30% relative humidity. | Uteroplacental blood flow. | The fetal temperature increased by 1.39 ± 0.12 °C, more than the maternal temperature increase of 1.19 ± 0.15 °C. there was a significant rise in uterine blood flow during hyperthermia (p = 0.006). Umbilical blood flow did not change significantly, but minor changes correlated with decreased fetal arterial Pco2. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: Low (failed to report all results). |
Arora et al., 1979 [39] Fetal and Placental Responses to Artificially Induced Hyperthermia in Rats United States RCT | Eight groups of six to eight outbred nulliparous Spartan female rats weighing 250–275 g. | Various stages of pregnancy. | Pregnant rats were heat-stressed on Gestation Days 4, 6, 8, 10, 12, 14, 16, or 18 for 90 min in the morning and 45 min in the afternoon at 43–44 °C in an incubator chamber. | Placental weight | Heat treatment significantly suppressed maternal weight gain and reduced embryo survival when applied on Day 4 of pregnancy. Placentas from Day 6–10 treatment groups were significantly heavier than controls, showing extensive thickening and necrosis of decidua basalis. Although the impact on fetal circulation is unclear, most fetuses associated with heat group placentas were smaller than controls. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Bell et al., 1987 [40] Some aspects of placental function in chronically heat-stressed ewes United States Non-RCT | Group 1: experimental group (heat stress) of five single-pregnant Columbia-Rambouillet crossbred ewes. Group 2: five single pregnant ewes from the same stock not exposed to heat. | Between Days 42–54 and 120 of gestation (mid and late) | In the climatic chamber, the dry bulb air temperature was maintained at 38–40 °C for 9 h daily and 30–32 °C for the remaining 15 h, with relative humidity at 40–50%. | Uteroplacental blood flow, placental weight. | Heat exposure significantly reduced placental weight, uterine and umbilical blood flows, and placental glucose transfer capacity. These reductions were highly correlated with placental weight. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Dada et al., 2023 [41] Placental Development and Physiological Changes in Pregnant Ewes in Silvopastoral (SP) and Open Pasture (OP) Systems during the Summer Brazil RCT | Twenty-four pregnant Dorper × Santa Inês crossbred ewes. They were divided into groups of 12 animals each and subjected to two treatments according to the rearing systems: the silvopastoral (SP) system and the open pasture (OP) system. | Third trimester 50 days gestation to 123.4 days gestation (mid and late). | In the OP, females remained in the open air without shade, while in the SP, they had tree shade. Both systems were stressful but the SP system had a lower air temperature than the OP system (26.0 ± 0.38 °C vs. 26.9 ± 0.41 °C; p = 0.0288). The microclimate of both environments was evaluated by studying air temperature (AT, °C), black globe temperature (BGT, °C), dew point temperature (DPT, °C), wind speed (WS, m/s), and relative humidity (RH, %). | Placental anatomy (placental mass, placental area, and the number of cotyledons were counted). | There was no system effect (OP vs. SP) on the total area of cotyledons per placenta, the area, and the mass of the chorionic membrane (p = 0.8456, p = 0.7178, and p = 0.9092, respectively). | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Dreiling et al., 1991 [38] Maternal Endocrine and Fetal Metabolic Responses to Heat Stress United States RCT | Pregnant ewes of mixed breeding. | Total of 110–130 days gestation (mid gestation). | Temperature of 24 °C for 40 min then 48 °C for 75 min daily. | Uteroplacental blood flow. | After 40 min, UBF dropped to 70% of the control rate. Fetuses from heat-stressed ewes weighed 82% of those from normal conditions. Heat-induced ADH or OT secretion may significantly impact uteroplacental perfusion in near-term fetuses. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Early et al., 1991 [42] Chronic heat stress and prenatal development in sheep: II. Placental cellularity and metabolism United States RCT | A total of 13 pregnant Suffolk ewes. Ewes were then assigned by BW and litter size to either a thermoneutra18 (TN) or heat9 (H) treatment beginning on Day 64 of gestation. | Total of 60–141 days gestation (mid and late gestation). | Pregnant ewes subjected to either thermoneutral (18 to 20 °C, 30% humidity, n = 7) or hot (H, 30 to WC, 40% humidity, n = 5) temperatures. | Placental weight and gene expression | Fetal and placental weights, as well as protein, RNA, and DNA content, were significantly reduced (p < 0.001) in heat-stressed (H) ewes. Heat stress notably decreased total cell number and placentae size, with only a slight reduction in cell size. Maternal placenta and myoendometrium oxygen consumption remained unchanged. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
El-Sherbiny et al., 2022 [43] Exogenous L-arginine administration improves uterine vascular perfusion, uteroplacental thickness, steroid concentrations, and nitric oxide levels in pregnant buffaloes under subtropical conditions Egypt RCT | Pluri-parous (n = 12) pregnant buffaloes. | Mid-gestation: ~180–190 days. | In August 2021, during mid-Summer, the Temperature Humidity Index (THI) exceeded 85, indicating severe heat stress for the animals. Twelve buffalo were randomly assigned to two groups: one group received a 5 mg/kg BW intravenous bolus of L-arginine (L-Arg) (n = 6; ARG), a nitric oxide (NO) precursor, while the control group (n = 6; CON) received 25 mL of normal saline. Measurements were taken at various time points: −1, 0, 2, 4, 24, 48, 72, 96, and 120 h post-L-Arg administration. | Placental steroids and uteroplacental blood flow. | L-Arg improved uteroplacental thickness and uterine hemodynamics in heat-stressed buffalo cows. Combined uteroplacental thickness (CTUP) was higher (p < 0.05) in the ARG group at H96 to 120 and L-Arg enhanced NO levels and steroid production. Measurements of CTUP, MUA diameter, and Doppler hemodynamics were taken with B-mode and color Doppler ultrasonography. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Galan et al., 1999 [44] Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency United States RCT | Ten pregnant ewes—five ewes were housed in an environmental chamber beginning at 35 days’ gestation and were removed after 55 days of exposure (Heat 55). Five ewes served as a control group and were housed at 20 °C ambient temperature. | A total of 35–85 days gestation for the first group (Heat 55) and 35–115 days gestation for the second group (heat 80) (mid). | Temperature maintained at 40 °C for 18 h during the day and decreased to 35 °C at night and humidity kept between 35% and 40%. | Placental weight. | Both heat groups had significantly lower fetal and placental weights compared with those in the control group. The Heat 80 group had significantly lower fetal and placental weights compared with those of the Heat 55 group. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Galan et al., 1998 [45] Doppler velocimetry of growth-restricted fetuses in an ovine model of placental insufficiency United States RCT | Ten mixed-breed (Columbia-Rambouillet) ewes with singleton pregnancies were used for this study. Five ewes were housed in an environmental chamber for 55 days beginning at 35 days gestation and five ewes that served as controls were housed at 20 °C ambient temperature. | A total of 35–85 days gestation (mid-gestation). | Temperature maintained at 40 °C for 12 h during the day and decreased to 35 °C at night and humidity kept between 35% and 40%, for 55 days. | Placental weight and efficiency. | Heat-stressed fetuses had higher systolic/diastolic ratios and pulsatility index values in the umbilical artery and aorta (p < 0.033). Their placentas weighed less (181.9 ± 7.0 gm vs. 307.06 ± 22.2 gm; p = 0.002). These differences appeared after 80 days of gestation. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Guo et al., 2022 [37] Heat Stress Modulates a Placental Immune Response Associated with Alterations in the Development of the Fetal Intestine and Its Innate Immune System in Late Pregnant Mouse China RCT | ICR strains of female and male mice. | Late gestation. | The control (TN) group mice were kept at room temperature (24 ± 1 °C) and the HS group mice were kept in the artificial intelligence climate chamber (35 ± 1 °C). | Gene expression. | Data showed that maternal heat stress reduced the expression of genes linked to fetal intestinal development, potentially due to increased expression of cell cycle genes. It also inhibited genes related to the fetal intestinal innate immune system, possibly due to placental inflammatory responses. | Sequence generation: Low. Did not specify how control and intervention groups were comparable. Incomplete outcome data: High. Selective reporting: High. |
Guo et al., 2021 [36] Heat stress affects fetal brain and intestinal function associated with the alterations of the placental barrier in late pregnant mouse China RCT | Nineteen ICR strain mice. | E12 to E18 (mid to late gestation). | Parameters of 35 °C, 70% humidity artificial intelligence climate chamber (35 ± 1 °C). | Placental efficiency and gene expression. | Maternal heat stress harmed placental development, increased fetal deaths, and disrupted lipid metabolism. It up-regulated nutrient transport genes in the placenta but down-regulated them in the fetal intestine. TG levels rose in the placenta and fell in the fetal intestine, affecting fetal brain function and the serotonin system. | Sequence generation: Low. Did not specify how control and intervention groups were comparable. Incomplete outcome data: High. Selective reporting: High. |
Hensleigh and Johnson, 1971 [46] Heat Stress Effects During Pregnancy. I. Retardnation of Fetal Rat Growth United States RCT | Pregnant rats of the Holtzman strain were obtained on or before Day 5 of gestation. | Early stages of pregnancy (Days 7–11). | High ambient temperature (39 °C; 58% relative humidity) for 4 h/day on Days 7–11. Kept in the chamber where temperatures were controlled. | Placental Weight | Heat exposure reduced fetal and placental weight on Day 12. On Day 20, only fetal weight was reduced, even without stress after Day 11. Ovariectomized rats on estrone and progesterone had normal fetuses and larger placentas compared to controls. Heat stress caused a significant reduction in placental weight on Day 20 but fetal size remained normal. | Sequence generation: Low. Did not specify how control and intervention groups were comparable. Incomplete outcome data: High. Selective reporting: High. |
Nakamura et al., 2000 [34] Heat Produces Uteroplacental Circulatory Disturbance in Pregnant Rats through Action of Corticotropin-Releasing Hormone (CRH) Japan RCT | A total of 24 virgin female Wistar rats and 24 Wistar rats at 15–16 days gestation were studied. | Mid pregnancy | The environment was maintained at 21–23 °C with 50–60% humidity, with 12-h light (08:00–20:00) and 12-h dark cycles. Microwaves at 2 mW/cm2 power density and 2450 MHz were applied for 90 min using a microwave exposure device. | Uteroplacental blood flow was monitored by the hydrogen gas electrolytic method. | Higher uteroplacental blood flow in pregnant rats than uterine blood flow in virgin rats. Heat and α-helical CRH significantly affected uteroplacental blood flow in pregnant rats but not in virgin rats. Blood flow decreased significantly from 15 to 90 min in pregnant rats without α-helical CRH, with no change in those with α-helical CRH. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: Low (failed to report all results). |
Nanas et al., 2021 [47] Ultrasonographic findings of the corpus luteum and the gravid uterus during heat stress in dairy cattle Greece NON-RCT | A total of 19 pregnant dairy cows (Winter group (n = 9) and Summer group (n = 10)). | Mid-pregnancy 90–110 days. | During the cool period of October to April (examined in March) and warm period of May to September (examined mid-August), the farm was equipped with an electronically operating cooling system and automatic activation of fans and sprinklers. Temperature humidity index (THI) was also measured. | Uteroplacental blood flow (the umbilical and uterine artery diameters and hemodynamic parameters in the vessels were calculated using the pulse wave doppler). | Seasonal variations did not affect hemodynamic parameters, uterine artery diameter, or placentome length. The grey-scale intensity and low color flow in placentomes were higher in Winter. Group S had lower umbilical artery diameter and blood volume than group W. Uterine artery blood flow was unaffected. In humans, brief late-pregnancy heat stress increases heart rate but not uterine vascular resistance. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Olivier et al., 2021 [48] Maternal, Placental, and Fetal Responses to Intermittent Heat Exposure During Late Gestation in Mice Australia RCT | 21 C57BL/6J mice | Fetal and placental tissues were collected at E18.5 (late gestation). | Three groups were studied: 1. SH Group (n = 7) Housed at 22 °C from E0.5 to E18.5; 2. TNZ Group (n = 7): Housed at 29 °C (thermoneutral zone) from E0.5 to E18.5; 3. HW Group (n = 7): Housed at 29 °C until E15.5, then placed in a 37 °C incubator from 09:00 to 17:00 on E15.5, E16.5, and E17.5, and returned to 29 °C for the rest of the time. Temperatures were 29.2 ± 0.5 °C in the warming cabinet and 37.7 ± 0.5 °C in the incubator. | Placental weight and efficiency; gene expression; and placental anatomy. | Housing temperature significantly affected placental weight, which was 16% lower in the heat exposure group than in the TNZ group due to a smaller labyrinth zone. Vegfa expression was 37% lower in the heat exposure group compared to the SH group. The expressions of Hsd11b2, Slc2a3, Slc38a2, and Slc38a4 were unchanged. In the fetal brain, Hif1α expression was 45% lower in the heat exposure group than in the TNZ group (p < 0.05). | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Padmanabhan et al., 2005 [49] Histological, histochemical and electron microscopic changes of the placenta induced by maternal exposure to hyperthermia in the rat United Arab Emirates RCT | Wistar rats n = 34: n = 14 at 41 °C, n = 10 at 42 °C, and n = 10 controls. | GD9–GD20—when embryos were at the beginning of organogenesis (mid and late Gestation). | Temperature of 41 °C for one group and 42 for the other for one hour on GD9 polypropylene cage and put in an incubator chamber pre-heated to 41 °C (n = ¼ 14) or 42 °C (n = ¼ 10) for 1 h. | Placental weight and placental anatomy. | Most placentas in the hyperthermia groups (82%) had a white fibrinoid patch at the margin. Only the 42 °C group’s placentas were lighter than the controls. Heat-stressed embryos had thicker decidua basalis, with more pronounced glycogen cell degeneration in the 42 °C group than the 41 °C group, leading to cyst formation in the basal zone. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Regnault et al., 1999 [50] Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency United States NON-RCT | A total of 14 pregnant 2–3-year-old Columbian Rambouillet ewes with a single fetus. | Between Days 37 and 93 of pregnancy (mid-gestation). | Temperature of 40 °C for 12 h then 35 °C for 12 h, 30–40% relative humidity. Hyperthermic treatment chamber. | Placental weight and efficiency and gene expression. | Chronic heat stress reduced progesterone and ovine placental lactogen (oPL) levels in ewes but did not significantly affect oPL mRNA or protein in cotyledonary tissue compared to TN ewes. Prolactin levels were four times higher in heat-stressed ewes (p < 0.0001) while placental weights were not significantly affected. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Silva et al., 2020 [51] Heat stress affects the expression of key genes in the placenta, placental characteristics, and efficiency of Saanen goats and the survival and growth of their kids Brazil RCT | A total of 46 Saanen goats were used: 14 primiparous and 32 multiparous. | The last 60 days of pregnancy until the first colostrum suckling. | The subtropical area has a 23 °C average temperature, 73% humidity, a rainy season from November to March, and 1300–2000 mm annual rainfall. Data were collected between June and September. Goats were in a control group (CT; n = 23) or heat-stressed group (HS; n = 23) in a chamber at 37 °C and 60–70% humidity from 08:00 to 16:00 h, with conditions returning to normal after that. | Placental weight and efficiency; placental steroids; and placental gene expression. | Heat-stressed (HS) goats had longer placenta delivery times, more cotyledons, lighter cotyledons, and lower placental efficiency compared to control (CT) goats. HS goats showed higher MC2R and NR3C1 gene expression, lower HSD11B2 expression, and higher HSPA1A expression. There were no effects on NR3C2, HSP1, HSPD1, or HSPB1 gene expression and HSD11B1, CRH, and CRHR1 were not expressed in either group. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Vaha-Eskeli et al., 1992 [52] Responses of placental steroids, prostacyclin, and thromboxane A2 to thermal stress during pregnancy Finland NON-RCT | Group 1: n = 15 healthy non-pregnant women; Group 2: n = 23 women 13–14 weeks pregnant; Group 3: n = 23 women 36–37 weeks pregnant; n = 47. | Early gestation (Group 2) and late gestation (Group 3). | The sauna protocol involved heating at 70 °C for 20 min with 15% humidity, followed by a 45-min recovery period at 21–23 °C. Rectal and skin temperatures were measured using an electric thermometer (TE3, Electrolaboratoriet Ellab A/S, Denmark). | Placental Steroids | The small changes in proteinoids and placental steroids due to heat stress appear not to negatively affect fetal well-being. The slight increase in placental steroids likely reflects metabolic changes rather than enhanced uteroplacental blood flow. In group II, E levels peaked during stress (15–40 min, 11%, p < 0.005) and remained elevated during recovery (p < 0.01). | Sequence generation: High. Incomplete outcome data: High. Selective reporting: Low (failed to report all results). |
Vatnick et al., 1991 [53] Effect of Heat Stress on ovine placental growth in early pregnancy United States RCT | A total of 11 Ditocous Dorset ewes. | Between days 50 and 75 of gestation. | Temperature of 40 °C dry bulb from 8:00 to 17:00 h and 30 °C dry bulb for the remainder of the day. Relative humidity was not controlled in either room but never exceeded 50% during the entire experiment. | Placental weight. | Heat reduced placental weight by 19% but did not affect fetal weight. Placental DNA and protein concentrations, as well as protein/DNA ratios, were similar between groups. Total Placental DNA content was lower in heated ewes, indicating fewer cells, although the DNA synthesis rate tended to be higher. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Walker et al., 1995 [54] Cardiovascular responses to heat stress in late gestation fetal sheep Australia NON-RCT | Seven pregnant ewes. | A total of 130–136 days gestation (late gestation). | To assess the impact of raising environmental temperature from 20 °C to 43 °C for 8 h at 30–60% relative humidity on uteroplacental blood flow and cardiac output distribution, 15 µm diameter radioactive microspheres were used in temperature-controlled rooms. | Uteroplacental blood flow and placental anatomy (the counts for all cotyledons were subsequently combined to determine the maternally derived placental blood flow). | Heat stress did not affect blood flow to the fetal or maternal sides of the placenta, indicating that perfusion-dependent heat transfer from fetus to mother does not increase under hyperthermic conditions. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Zhao et al., 2022 [55] Heat stress of gilts around farrowing causes oxygen insufficiency in the umbilical cord and reduces piglet survival Australia RCT | Sixteen pregnant primiparous sows (gilts). | A total of 110 days—farrowing completion (late gestation). | Pregnant gilts were assigned to either a thermoneutral control (CON, n = 8; constant 20 °C) or cyclical heat stress (HS) condition (30 °C from 09:00 to 17:00 h and 28 °C from 17:00 to 09:00 h) in a climate-controlled facility at the University of Melbourne. | Uteroplacental blood flow and placental anatomy. | Heat-stressed gilts took longer to expel placentas (p = 0.003) and had higher stillbirth rates (p < 0.001). Surviving piglets had lower umbilical vein oxygen levels (p = 0.04) and oxygen saturation (p = 0.03), with higher lactate levels (p = 0.07). No retained piglets or placentas were observed in controls. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Zhao et al., 2020 [56] Controlled elevated temperatures during early-mid gestation cause placental insufficiency and implications for fetal growth in pregnant pigs Australia RCT | n = 15 pregnant pigs; n = 7 thermoneutral; and n = 8 cyclic elevated temperature conditions. | Mid-gestation: d40–d60. | Pigs were housed under constant thermoneutral (n = 7) or cyclic elevated temperatures (33 °C from 09:00 to 17:00 h and 28 °C from 17:00 to 09:00 h; n = 8). Thermal stress was assessed weekly by measuring skin temperature and respiration rate at multiple times. | Placental weight and efficiency; placental anatomy; and gene expression. | ET fetuses had larger placentas (p = 0.041) but lower placental efficiency (p = 0.013). They showed reduced muscle fiber density (p = 0.032) and a thicker placental epithelial layer (p = 0.017). ET decreased GLUT-3 mRNA (p = 0.026) and increased IGF-2 mRNA (p = 0.037). Plasma progesterone was lower in ET pigs (p = 0.050), but progesterone per unit placental mass was unaffected. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
Zhao et al., 2021 [57] Maternal Heat Stress Alters Expression of Genes Associated with Nutrient Transport Activity and Metabolism in Female Placentae from Mid-Gestating Pigs Australia RCT | Ten large White × Landrace female pigs were selected from a commercial piggery and artificially inseminated on Day 0 at a farm. | A total of 40–60 days gestation (early to mid-gestation). | On Day 40 of gestation, pregnant pigs were exposed to either constant thermoneutral conditions (CON; n = 5; 20 °C) or cyclic heat stress (HS; n = 5; 33 °C from 09:00 to 17:00 h and 28 °C from 17:00 to 09:00 h) for 3 weeks in a climate-controlled facility, simulating Australian Summer conditions. | Placental weight and efficiency; placental anatomy; and placental gene expression. | On Day 60 of gestation, maternal heat treatment tended to decrease fetal weight (p = 0.08) but increase placental weight (p = 0.053) and surface area (p = 0.09). Placental efficiency was lower in the heat-stressed group (p = 0.023). Heat stress upregulated 35 genes and downregulated 134 genes, particularly those related to transporter and catalytic activities. | Sequence generation: High. Incomplete outcome data: High. Selective reporting: High. |
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Ramirez, J.D.; Maldonado, I.; Mach, K.J.; Potter, J.; Balise, R.R.; Santos, H. Evaluating the Impact of Heat Stress on Placental Function: A Systematic Review. Int. J. Environ. Res. Public Health 2024, 21, 1111. https://doi.org/10.3390/ijerph21081111
Ramirez JD, Maldonado I, Mach KJ, Potter J, Balise RR, Santos H. Evaluating the Impact of Heat Stress on Placental Function: A Systematic Review. International Journal of Environmental Research and Public Health. 2024; 21(8):1111. https://doi.org/10.3390/ijerph21081111
Chicago/Turabian StyleRamirez, Jazmin D., Isabel Maldonado, Katharine J. Mach, Jonell Potter, Raymond R. Balise, and Hudson Santos. 2024. "Evaluating the Impact of Heat Stress on Placental Function: A Systematic Review" International Journal of Environmental Research and Public Health 21, no. 8: 1111. https://doi.org/10.3390/ijerph21081111