Yadav Pankaj, Mishra Jay S, Kumar Sathish
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America.
J Environ Sci Public Health. 2023;7(3):131-139. doi: 10.26502/jesph.96120193. Epub 2023 Aug 3.
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, [C]-PFOA (9.4 pmol/kg) was given intravenously, and subsequently, 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 and was significantly decreased, while and 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.
全氟辛酸（PFOA）是一种持久性合成化学物质，会损害人体健康。最近的研究表明，PFOA的生物累积性增强，尤其是在患有先兆子痫的孕妇中。由于先兆子痫孕妇的血浆睾酮水平升高，我们推测孕期的高雄激素状况可能会阻碍PFOA的清除，并导致其体内负担加重。从妊娠第15天到第20天，对怀孕的斯普拉格-道利大鼠进行皮下注射溶剂或丙酸睾酮，以使血浆睾酮水平升高两倍，类似于先兆子痫患者的水平。在妊娠第16天，静脉注射[C]-PFOA（9.4 pmol/kg），随后测量母体血液、尿液、粪便和组织中的C放射性。PFOA主要通过尿液排出；然而，睾酮水平升高的怀孕大鼠尿液中排出的PFOA比对照组少。PFOA的粪便排泄量极少，两组之间无显著差异。睾酮水平升高的怀孕大鼠中，PFOA的总清除量（尿液加粪便）显著降低了12%。在对照组中，PFOA在胎盘中的分布最高，其次是肾脏、肝脏、大脑、心脏、肺和脾脏。睾酮水平升高的怀孕大鼠这些组织中PFOA的浓度比对照组高12%。此外，与对照组相比，睾酮水平升高的怀孕大鼠中，[具体基因名称1]和[具体基因名称2]的肾脏表达显著降低，而[具体基因名称3]和[具体基因名称4]的表达显著增加。总之，母体睾酮水平升高会降低PFOA的尿液清除率，可能是通过改变肾脏转运蛋白的表达，导致怀孕大鼠体内PFOA组织浓度升高。
