Chronic exposure to perfluorononanoic acid impairs spermatogenesis, steroidogenesis and fertility in male mice

Abstract

Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that they are ubiquitous and persistent in the environment. Perfluorononanoic acid (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous acute exposure studies have shown the adverse effect of PFNA on the testis. The present study was aimed to examine the effect of chronic PFNA exposure, from prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male mice and to investigate the possible mechanism(s) of its action. PFNA (0.2 and 0.5 mg/kg) was orally administered to P male mice for 90 days from prepuberty (postnatal day [PND] 25) to adulthood (PND 114). Histologically, testes in PFNA‐treated mice showed non‐uniform degenerative changes in the seminiferous tubules. The treatment also had adverse effects on testicular expression of steroidogenic markers, serum levels of cholesterol and testosterone, sperm parameters and on litter size. A marked increase in the level of lipid peroxidation and decrease in the activities of antioxidant enzymes were observed in the testis of PFNA‐treated mice compared to controls. Further, a significant decrease in expression of proliferating cell nuclear antigen (PCNA) and in the number of PCNA‐positive cells, and an increase in expression of caspase‐3 were also noted in PFNA‐treated mice testis. In conclusion, the results suggest that chronic exposure to PFNA in male mice interferes with testosterone biosynthesis and causes oxidative stress in the testis, leading to alterations in spermatogenesis, sperm quality and fertility potential.

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

“…Consistent findings were observed following in utero exposure to PFOA [166]. Male reproductive toxicity, including effects on hormone levels and fertility was observed in PFNA treated mice [98] and gestational exposure to GenX and PFHxS resulted in lower testis weight and a weak but significant association with nipple retention in males, respectively [167,168].…”

“…Similarly, in vivo and in vitro studies have demonstrated that PFOS exposure results in oxidative stress, evidenced by the production of ROS, changes in antioxidant enzymes, elevation of lipid peroxidation products and changes in Nrf2 [32,[95][96][97]. Increased lipid peroxidation and antioxidant enzyme activity were also observed in mouse testes following PFNA exposure [98].…”

Effect of Quinalphos on Testes of Long Day Seasonal Breeder Golden Hamster, Mesocricetus auratus

“…Immediately after sacrificing the animal, one of the epididymis from each animal was dissected out and used for analysis of sperm counting and viability assay. The cauda epididymal sperm count was carried out according to the World Health Organization (1999) laboratory manual.MTT (3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay for viability of sperm was performed following the method published elsewhere (Singh and Singh, 2018). Briefly, after the sperm count, the sperm suspension was immediately diluted to obtain a concentration of 4 × 10 6 spermatozoa/ ml.…”

Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes

“…Humans are exposed to PFAAs through different routes such as food and water contamination, dermal contact, household dust and air inhalation (Su et al, ). Toxicological studies have shown adverse effects of these chemicals on many physiological processes of the body such as hepatic (Wang, Yan, Zhang, Zhang, & Dai, ), immune (Fang, Zhang, Feng, Zhao, & Dai, ), nervous (Fang, Wu, Li, Yuan, & Wang, ), and reproductive and endocrine systems (Foresta, Tescari, & Di Nisio, ; Singh & Singh, ; Singh & Singh, ). Because of these reasons, PFAAs have received much attention, and concern has thus arisen for their potential health risk to humans and wildlife.…”