PMID- 37654976 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230905 IS - 2575-9612 (Electronic) IS - 2575-9612 (Linking) VI - 7 IP - 3 DP - 2023 TI - Elevated Maternal Testosterone Levels Alter PFOA Elimination and Tissue Distribution in Pregnant Rats. PG - 131-139 LID - 10.26502/jesph.96120193 [doi] AB - Perfluorooctanoic acid (PFOA) is an enduring synthetic chemical that harms human health. Recent studies indicate heightened bioaccumulation of PFOA, particularly in pregnant women experiencing preeclampsia. Since plasma testosterone levels are elevated in pregnant women with preeclampsia, we hypothesized that hyperandrogenic conditions during pregnancy may hinder PFOA elimination and contribute to their higher body burden. Pregnant Sprague-Dawley rats were s/c injected with vehicle or testosterone propionate from gestational day (GD) 15 to 20 to increase plasma testosterone levels by 2-fold, similar to levels in preeclampsia. On GD 16, [(14)C]-PFOA (9.4 pmol/kg) was given intravenously, and subsequently, (14)C radioactivity was measured in maternal blood, urine, feces, and tissues. PFOA was primarily eliminated through urine; however, less PFOA was excreted in urine of pregnant rats with elevated testosterone levels than controls. Fecal excretion of PFOA was minimal and did not significantly differ between groups. The total elimination of PFOA (urine plus feces) was significantly reduced by 12% in pregnant rats with elevated testosterone levels. In controls, PFOA distribution was highest in placenta, followed by the kidneys, liver, brain, heart, lungs, and spleen. Pregnant rats with elevated testosterone levels displayed 12% higher concentrations of PFOA in these tissues than controls. Furthermore, the renal expression of Oat2 and Oat3 was significantly decreased, while Oatp1 and Oat-k expression was significantly increased in pregnant rats with elevated testosterone levels than controls. In conclusion, elevated maternal testosterone levels decrease urinary elimination of PFOA, possibly through altered expression of renal transporters leading to increased tissue concentrations of PFOA in pregnant rats. FAU - Yadav, Pankaj AU - Yadav P AD - Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America. FAU - Mishra, Jay S AU - Mishra JS AD - Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America. FAU - Kumar, Sathish AU - Kumar S AD - Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America. AD - Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America. AD - Endocrinology-Reproductive Physiology Program, University of Wisconsin, Madison, Wisconsin, United States of America. LA - eng GR - R01 ES033345/ES/NIEHS NIH HHS/United States GR - R01 HL134779/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20230803 PL - United States TA - J Environ Sci Public Health JT - Journal of environmental science and public health JID - 9918626489006676 PMC - PMC10470210 MID - NIHMS1923912 OTO - NOTNLM OT - Bioaccumulation OT - Kidney OT - Perfluorooctanoic acid OT - Pregnant rats OT - Testosterone OT - Transporters COIS- Conflicts of interest: None EDAT- 2023/09/01 06:43 MHDA- 2023/09/01 06:44 PMCR- 2023/08/31 CRDT- 2023/09/01 04:04 PHST- 2023/09/01 06:44 [medline] PHST- 2023/09/01 06:43 [pubmed] PHST- 2023/09/01 04:04 [entrez] PHST- 2023/08/31 00:00 [pmc-release] AID - 10.26502/jesph.96120193 [doi] PST - ppublish SO - J Environ Sci Public Health. 2023;7(3):131-139. doi: 10.26502/jesph.96120193. Epub 2023 Aug 3.