Exposure to either Bisphenol A or S Represents a Risk for Crucial Behaviors for Pup Survival, Such as Spontaneous Maternal Behavior in Mice

Abstract

Introduction: Maternal behavior depends on a multitude of factors, including environmental ones, such as Endocrine Disrupting Chemicals (EDCs), which are increasingly attracting attention. Bisphenol A (BPA), an EDC present in plastic, is known to exert negative effects on maternal behavior. Bisphenol S (BPS), a BPA substitute, seems to share some endocrine disrupting properties. In this study, we focused on the analysis of the effects of low-dose (i.e., 4 µg/kg body weight/day, EFSA TDI for BPA) BPA or BPS exposure throughout pregnancy and lactation in mice.

Methods: We administered adult C57BL/6 J females orally BPA, BPS, or vehicle from mating to offspring weaning. We assessed the number of pups at birth, the sex ratio, and the percentage of dead pups in each litter, and during the first postnatal week, we observed spontaneous maternal behavior. At the weaning of the pups, we sacrificed the dams and analyzed the oxytocin system, known to be involved in the control of maternal care, in the hypothalamic magnocellular nuclei.

Results: At birth, pups from BPA-treated dams tended to have a lower male-to-female ratio compared to controls, while the opposite was observed among BPS-treated dams' litters. During the first postnatal week, offspring mortality impacted differentially in the BPA and BPS litters, with more female dead pups among the BPA litters, while more male dead pups in the BPS litters, sharpening the difference in the sex ratio. BPA- and BPS-treated dams spent significantly less time in pup-related behaviors than controls. Oxytocin immunoreactivity in the paraventricular and supraoptic nuclei was increased only in the BPA-treated dams.

Discussion/conclusions: Alterations in maternal care, along with the treatment itself, may affect, later in life, the offspring's physiology and behavior. Exposure to BPs during sensitive developmental periods represents a risk for both dams and offspring, even at low environmentally relevant doses, through the functional alteration of neural circuits controlling fundamental behaviors for pup survival, such as maternal behaviors.

Keywords: Endocrine disrupting chemicals; Environmentally low doses; Oxytocin; Paraventricular nucleus; Supraoptic nucleus.