Transgenerational effects of exposure to an EDC mixture on maternal behavior and sexual development

Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to produce transgenerational inherited modifications. A rising public health challenge is to determine the effect of complex mixtures of EDCs on the developing body throughout generations. In this study we aim to determine the transgenerational effects of a mixture of EDCs on female sexual development and behavior.
Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and estrogenic EDCs at low doses. Sexual development (sex ratio, vaginal opening (VO), GnRH interpulse interval and estrous cyclicity) as well as maternal behavior were measured from F0 to F3 generation.
In utero exposed females (F1) when raising pups, showed an increased time resting alone and decreased time licking and grooming pups. F2 (animals whose germlines were exposed) and F3 exposed animals showed an altered sex ratio in favor of males and F2 and F3 females showed delayed VO. F2 and F3 females followed for estrous cyclicity showed significant alterations of estrous cyclicity characterized by a significant increase in the time spent in estrus and decreased time spent in diestrus. F3 females presented an increased GnRH interpulse interval compared to control.
Overall, data shows that gestational exposure to an EDCs mixture can affect maternal behavior and sexual development during several generations. The effects observed in the F3 generation suggest the presence of transgenerational epigenetic mechanisms.