Workshop Report 30

The lack of Transgenerational Inheritance of Anti-androgenic effects after Vinclozolin Treatment

Roland Buesen
Toxicologist and study director, BASF, Germany
Dr Buesen built on the previous presenter’s discussions about the difficulty in reproducing epigenetics studies, exemplified by BASF’s research project to reproduce the results of the Anway et al studies (2005; 2008). These studies reported that Vinclozolin administered to pregnant rats induced an adult phenotype in the F1 generation of decreased spermatogenic capacity (cell number and variability); increased spermatogenic cell apoptosis and decreased male fertility – and that these effects were transferred to males of F2 and subsequent generations. The BASF study (Schneider et al, 2013) examined the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100 mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4 mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring were observed as signs of anti-androgenicity at 100 mg/kg bw/d. However, F1-F3 males of the high-dose group developed normally to sexual maturity (slight delay in pubertal onset in F1 males) and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin’s anti-androgenic effects was not evident in outbred Wistar rats.