Alterations in Gene Expression and Testosterone Synthesis in the Testes of Male Rats Exposed to Perfluorododecanoic Acid

Abstract

Perfluorododecanoic acid (PFDoA, C12), a synthetic perfluorinated chemical containing 12 carbons, has broad industrial applications and has been detected in sera from humans and other animals; however, few reports have addressed the effects of PFDoA exposure on male reproduction. In the present study, the effects of PFDoA exposure on testes ultrastructure, testosterone levels, and steroidogenic gene expression were investigated. Male rats were orally dosed for 14 days with 1, 5, or 10 mg PFDoA/kg/day or with vehicle. Absolute testis weight was diminished at the highest dose while relative testes weight was markedly increased at doses of 5 and 10 mg/kg/day. Total serum cholesterol levels were significantly increased at the highest dose. While luteinizing hormone was significantly decreased at the highest dose, testosterone was markedly decreased at doses of 5 and 10 mg PFDoA/kg/day. Serum levels of follicle-stimulating hormone were not significantly affected by PFDoA, and estradiol levels were markedly decreased only at 5 mg/kg/day. Leydig cells, Sertoli cells, and spermatogenic cells from rats that received 5 or 10 mg PFDoA/kg/day, exhibited apoptotic features including dense irregular nuclei, condensed chromatin, ill-defined nuclear membranes, and abnormal mitochondria. PFDoA exposure resulted in significant declines in mRNA expression of several genes involved in cholesterol transport and steroid biosynthesis at doses of 5 and 10 mg PFDoA/kg/day, while the gene expression of luteinizing hormone receptor and aromatase was not significantly changed. Our results demonstrate that PFDoA affects the reproduction function of male rats via alterations in steroidogenesis genes, testosterone levels, and testes ultrastructure.

Potential Ameliorative Role of N-Acetylcysteine Against Testicular Dysfunction Induced by Titanium Dioxide in Male Albino Rats

“…The cytochrome P-450 aromatase enzyme, the ratelimiting enzyme in estradiol biosynthesis, it catalyzes the estradiol sythesis from testosterone. The present study demonstrated that aromatase mRNA levels decreased in TiO2 administered rats and NAC normalized aromatase expression in a way to control estradiol biosynthesis (Shi et al, 2007). It has been shown that NAC decrease diazinon induced oxidative stress in rat testes (Oksay et al, 2013) and improved semen quality and canine fertility (Michael et al 2010).…”

Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

“…Previous studies reported that certain PFCs, such as PFOA, PFDA, and PFDoA decreased serum testosterone level in rats under toxicological dosages (Bookstaff et al, 1990;Martin et al, 2007;Shi et al, 2007Shi et al, , 2009). The serum PFCs concentrations (5 μg/mL to 260 μg/mL) measured in those dosed animals were in the same range as the concentrations of FTOHs applied to H295R cells in this study Martin et al, 2007).…”

“…Therefore, the down-regulation of mRNA expression and protein abundance could lead to the decreased steroid hormone production. It has been previously demonstrated that exposure to PFDoA significantly decreases StAR and P450scc (CYP11A) mRNA expression and protein abundance resulting in decreased serum testosterone concentrations in male rat testes (Shi et al, 2007(Shi et al, , 2009). The authors speculated that decreased testosterone level, at least in part, was due to the reduced expression of StAR and CYP11A.…”

“…Furthermore, decreases in mRNA expression and the protein abundance of steroidogenic enzymes were observed after acute and chronic perfluorododecanoic (PFDoA) exposure in male rats. This resulted in significantly lower concentrations of plasma testosterone, compared to unexposed animals (Shi et al, 2007(Shi et al, , 2009). These studies suggest that PFCs can affect steroidogenic activities, however, the cellular mechanisms remain unknown.…”

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

“…In addition to receptor-mediation capacity, PFCs have also been shown to alter hormone production by affecting steroidogenic tissue in reproductive organs [16,17,28]. To explore the mechanism of steroidogenesis disruption by PFOS, concentrations of two steroid hormones (T and E2) in the culture medium and relative responses of 10 genes involved in the steroidogenic pathway were measured in H295R cells.…”