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Abstract :
[en] Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to involve transgenerational mechanisms in their effects. Environmentally relevant mixtures of EDCs pose a public health challenge and their effects on developmental endpoints throughout generations remain largely unknown. In this study we aim to determine the transgenerational effects of a mixture of EDCs on maternal behavior and female sexual development in the offspring.
Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and/or estrogenic EDCs at low doses. Sexual development (sex ratio, vaginal opening (VO), pulsatile GnRH secretion from hypothalamic explants and estrous cyclicity) as well as maternal behavior were studied from F0 to F3 generation.
When adult females exposed In utero (F1) were raising pups, they showed an increased time resting alone and a decreased time licking and grooming pups. In F2 (animals whose germlines were exposed) and F3 generations after exposure, an altered sex ratio was observed in favor of males and F2 and F3 females showed delayed VO. These sexually delayed F2 and F3 females subsequently 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, the data shows that gestational and lactational exposure to an EDCs mixture can affect maternal behavior in F1 generation and sexual development during several generations. The effects observed in the F3 generation suggest the involvement of indirect and possibly epigenetic mechanisms.
