Collins Antwi-Boasiako^1,2, M. Estefania Gonzalez Alvarez¹, Bridget M. Buol¹, Omotoyosi Adeyanju^1,2, Lance H. Baumgard¹, Aileen F. Keating^1,2 

¹Department of Animal Science, Iowa State University 

²Interdepartmental Toxicology Program, College of Veterinary Medicine, Iowa State University 

Perfluorooctanoic acid (PFOA) is a member of a large group of synthetic organic chemicals called per- and poly-fluoroalkyl substances (PFAS). The unique properties of PFAS make them very useful in the manufacturing industry, but their persistence, bio-accumulative potential, and health effects make them of high concern. Heat stress (HS) is an environmental stressor that causes female infertility. The individual ovarian impacts of HS and PFOA have been studied, but little is known about the combined effects of these stressors on the ovary. Thus, in this study, the impact of an environmentally relevant dose of PFOA (70 ng/kg/BW) on ovarian functions under thermal neutral (TN) and HS conditions was studied with the hypothesis being that HS would be additive to PFOA effects on the ovary. The study was divided into three periods: during period 1, post-pubertal gilts were assigned to one of four groups: TN control (TC; n = 12); TN PFOA (70 ng/kg/BW TP; n = 12); HS control (HC; n = 12); and HS PFOA (70 ng/kg/BW HP; n = 11) and experienced either thermal neutral (TN; 20.38 ± 0.20 °C; TC and TP) or heat stress (32.0 ± 0.2 °C for 12 h and 26.6 °C for 12 h; HC and HP) for 19 d. Pigs were estrus synchronized to ensure that HS and PFOA exposure occurred during the follicular phase of the estrous cycle and ovaries were collected immediately prior to ovulation. The induction of HS was confirmed by elevated rectal temperature (P < 0.05) and high respiration rate (P < 0.05). Neither HS nor PFOA affected uterine weight, dominant follicle size, or vulva area. PFOA decreased ovarian weight in the TN (P = 0.04) but not HS females. Prior to the follicular phase, HS increased (P < 0.05) serum estradiol (E2) but there was no effect of HS on serum progesterone (P4). At the end of the follicular phase, serum E2 and P4 were unaffected by HS or PFOA exposure. In follicular fluid, PFOA decreased E2 concentration (P = 0.046), but there was no effect on P4 concentration. PFOA exposure decreased abundance of steroidogenic proteins CYP19A1 (P = 0.04) and 3βHSD (P = 0.009), but there was no effect on ovarian CYP11A1 abundance. Exposure to PFOA decreased (P = 0.002) microsomal epoxide hydrolase protein, but there was no effect on the abundance of cytochrome P450 isoform 1BA, glutathione S-transferase isoform pi, or ATP Binding Cassette Subfamily C Member 1. These data support that PFOA alone and in conjunction with HS can affect the ovary function in ways that could impair female reproductive function. Supported by the Iowa State University Presidential Interdisciplinary Research Seed Grant Program to AFK.