The effect of perfluorododecanonic acid on endocrine status, sex hormones and expression of steroidogenic genes in pubertal female rats.

Perfluorododecanoic acid (PFDoA), one of a number of commercially important perfluoroalkyl acids, has been detected in sera from humans and other animals; however, the effects of PFDoA on female reproduction remain unclear. To assess the impact of PFDoA on puberty and endocrine status, we exposed weaned pre-pubertal female rats to PFDoA, administered orally at doses of 0, 0.5, 1.5 and 3mg/kg-d for 28 days, and measured body weight, reproductive organ weight and morphology, pubertal indicators, endocrine hormones, total serum cholesterol levels and steroidogenic enzyme gene expression. At 3mg/kg-d, PFDoA significantly decreased body weight and serum estradiol levels, increased cholesterol levels (p<0.05), and altered ovarian expression of genes responsible for cholesterol transport and steroidogenesis, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme and 17-beta-hydroxysteroid dehydrogenase (p<0.05). PFDoA at the highest dose also reduced estrogen receptor alpha and beta expression levels in the ovary (p<0.05), whereas a lower concentration of PFDoA (0.5mg/kg-d) decreased estrogen receptor beta mRNA levels in the uterus (p<0.05). PFDoA treatment did not affect serum follicle-stimulating hormone or luteinizing hormone (LH) levels at any concentration, although PFDoA at 3mg/kg-d reduced LH receptor mRNA levels. There were no marked changes in sexual organ weight, age and weight at vaginal opening or first estrous cycle, or ovarian/uterine histology at any PFDoA concentration. These data show that PFDoA does not affect the endocrine status of pubertal rats, but at higher doses it does impact estradiol production and the expression of some key genes responsible for estrogen synthesis.