Effects of diethylstilbestrol exposure during gestation on both maternal and offspring behavior

Abstract

Endocrine disruption during gestation impairs the physical and behavioral development of offspring. However, it is unclear whether endocrine disruption also impairs maternal behavior and in turn further contributes to the developmental and behavioral dysfunction of offspring. We orally administered the synthetic non-steroidal estrogen diethylstilbestrol (DES) to pregnant female C57BL/6J mice from gestation day 11–17 and then investigated the maternal behavior of mothers. In addition, we examined the direct effects of in utero DES exposure and the indirect effects of aberrant maternal behavior on offspring using the cross-fostering method. In mothers, endocrine disruption during gestation decreased maternal behavior. In addition, endocrine disruption of foster mother influenced anxiety-related behavior and passive avoidance learning of pups regardless of their exposure in utero. The influence of DES exposure in utero, irrespective of exposure to the foster mother, was also shown in female offspring. These results demonstrate the risks of endocrine disruptors on both mother as well as offspring and suggest that developmental deficits may stem from both in utero toxicity and aberrant maternal care.

Low doses of 17α-ethinyl estradiol alter the maternal brain and induce stereotypies in CD-1 mice exposed during pregnancy and lactation

“…Thus, future studies should examine estrogen-sensitive endpoints, including those relevant to maternal behaviors, in the F1 generation. Although many studies focus on effects of maternal EDC exposures on offspring outcomes, evaluating the effect of treatment on the maternal brain and behavior of the mother is important, as alterations in maternal care may contribute to effects that are observed in offspring [112-114].…”

Developmental Exposure to Ethinylestradiol Affects Reproductive Physiology, the GnRH Neuroendocrine Network and Behaviors in Female Mouse

“…Therefore, disrupted maternal behavior observed in EE2-exposed females may be attributed to a direct effect of EE2 on target specific genes or central circuits such as POA, directly involved in maternal care behaviors. Nevertheless, we cannot rule out that an altered F0 maternal care could have influenced the behavioral outcomes of their offspring behaviors at adulthood, such as maternal care and anxiety level (Tomihara et al, 2015 ).…”

“…Indeed, developmental exposure to the estrogenic compound Bisphenol A (BPA) has previously been shown to alter maternal behavior of females exposed as a fetus or during their own pregnancy (Palanza et al, 2002 ). A recent study reported that diethylstilbestrol (DES) exposure during pregnancy modified maternal behavior of females and induced higher anxiety levels in adult offspring exposed during their prenatal development and receiving care from exposed or oil-treated mothers (Tomihara et al, 2015 ). This latest study showed two possible effects of perinatal exposure to disrupting events.…”

Developmental estrogen exposures and disruptions to maternal behavior and brain: Effects of ethinyl estradiol, a common positive control

“…We have additionally demonstrated effects of EE2 on dams exposed during pregnancy (Catanese and Vandenberg, 2017b) and BPS exposures in the F0 and F1 generation (Catanese and Vandenberg, 2017a; LaPlante et al, 2017) (Figure 8). While a number of additional studies demonstrate the profound effects of maternal exposures on the health of offspring, our work and that of others provides strong evidence that there are notable effects of treatment on the maternal brain and behavior of the mother, which can in turn, impact offspring (Cummings et al, 2010; Cummings et al, 2005; Tomihara et al, 2015). From an evolutionary perspective, maternal behavior is often defined in light of its importance for the survival of offspring, however, the importance of maternal care in humans stems from its contribution to the intellectual, physical, emotional and psychological development of children.…”