Parental exposure to 3-methylcholanthrene before gestation adversely affected the endocrine system and spermatogenesis in male F1 offspring

Abstract

The compound 3-methylcholanthrene (3-MC) is an environmental pollutant belonging to the PAHs, which reportedly have the potential to disrupt the endocrine systems of animals. In the present study, 4-week-old male and female mice were given 3-MC through their diet at a dose of 0.5 mg/kg of chow for 6 weeks before pregnancy. The first filial (F1) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 or 10 weeks (F1-5 W or F1-10 W), and the potential effects on the F0 and F1 offspring were evaluated. The results showed that the serum and testicular testosterone (T) levels and the genes involved in T synthesis in F0 males and male F1-5 W individuals born from female mice exposed to 3-MC were significantly decreased. In addition, histological analysis suggested that exposure to 3-MC significantly disrupted testicular morphology in F0 mice and in the offspring of female mice exposed to 3-MC. Further investigation revealed that genes involved in spermatogenesis, such as Phosphoglycerate kinase 2 (Pgk2), Glial cell derived neurotrophic factor (Gdnf), Myeloblastosis oncogene (Myb), DEAD box helicase 4 (Ddx4) and KIT proto-oncogene receptor tyrosine kinase (Kit), were suppressed in these mice. However, the adverse effects of parental 3-MC exposure on the adolescent mice were mitigated when they grew to adulthood, which was verified by studies on F1-10 W mice. Our results suggest that female exposure to 3-MC has the potential to disrupt the endocrine system and spermatogenesis in male offspring; nevertheless, the adverse effects might be mitigated with age.