(152) Anomalous High Temperature Exposure Effects on Mouse Ovarian Weight and Folliculogenesis

Luhan T. Zhou¹; Sophia Akinboro¹; Elnur Babayev¹

1. Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

Abstract Text: Increased frequency, duration, and intensity of extreme heat have immediate and direct impact on human physical and mental health. The impact of exposure to high temperatures on fertility and reproduction is an area of increasing concern. Although the negative impact of heat on spermatogenesis is well recognized, little is known about the impact of heat on ovarian folliculogenesis and aging. We examined two hypotheses: 1) exposure to an anomalous high temperature in reproductively adult mice impacts folliculogenesis, and 2) increased frequency of exposure to an anomalous high temperature during pregnancy and after birth impacts offspring development, their ovarian reserve, and reproductive aging. To test our hypotheses, we used a climate change model to apply predicted environmental changes in reproductively adult mice and a physiologically aging mouse model. CD-1 mice were housed/mated in temperature adjustable chambers at mouse thermoneutral temperature of 28°C. For the first hypothesis, the experimental group of adult mice 6-12 weeks old was exposed to 35°C for 1 or 4 days and ovaries were harvested immediately after exposure, compared to the control group that was continuously maintained at 28°C. For the second hypothesis, the experimental group was exposed to 35°C once every 7 days during pregnancy and after birth, compared to the control group which was exposed to 35°C once every 40 days. Offspring were harvested at postnatal day 6 (PND6), 6 weeks, and 3.5 months. Mouse body and ovary weights were measured at the time of harvest for both experiments. For the first hypothesis, body weights did not significantly differ between groups (control: 28.31±4.52g, 1 day: 28.31±3.12g, 4 day: 27.45±2.88g; p >0.05). Average ovary weights also did not differ between control and the 1 day heat exposed group (9.04±2.19mg vs. 9.61±1.00 mg; p >0.05), but did significantly reduce in the 4 day heat exposed group (6.50±0.67mg; p< 0.05). When normalized to body weight, the significant decrease was maintained in the 4 day heat exposed group. For the second hypothesis, at PND6 and 6 weeks, a significant decrease in body weight of heat stressed animals was noted (4.95±0.35g vs. 3.79±0.26g; p< 0.01 and 26.93±0.61g vs. 23.39±0.57g; p< 0.01); however, litter size normalization rendered these results insignificant. Ovary weight at 6 weeks timepoint also significantly decreased in the experimental group (5.16±0.36mg vs. 3.87±0.20mg; p< 0.05), but normalization again rendered the result insignificant. At 3.5 months, there was no significant difference in body weights both before and after litter size normalization (31.89±2.76g vs. 29.53±4.81g; p >0.05). Average ovary weight trended toward a decrease at this time point before and after litter size normalization (6.61±2.11mg vs. 5.09±1.39mg; p=0.07). No significant differences were noted in reproductive hormone (FSH, AMH and progesterone) levels or follicle numbers for the first hypothesis. Overall, our results demonstrate that increased duration of acute exposure to an anomalous high temperature of 35°C negatively impacts ovary weight. Studies are ongoing to uncover the impact of high temperature exposure on ovarian reserve and reproductive aging, which has implications for female fertility and overall health.

This work is supported by the Department of Obstetrics and Gynecology Start Up funds (EB).