Intergenerational and transgenerational effects of endocrine-disrupting chemicals in the offspring brain development and behavior

Abstract

Endocrine-disrupting chemicals (EDCs) are a group of substances that can alter normal body functioning by disrupting the various patterns of hormone secretion and action. Some of these substances are used as plasticizers (e.g., bisphenols and phthalates) and agrochemicals (e.g., vinclozolin). EDC exposure can occur by many routes, including oral by contaminated food and water, through the skin, inhalation, and by placental transfer from mother to fetus or mother to infant (via lactation). The increase in EDCs used by the industry has strongly impacted our health. An increasing number of scientific works have reported the effects of EDCs on cancer development, metabolism, heart disease, and fertility. Most recently, studies on EDCs effects on behavior and the developing brain are raising major concerns related to the formation of sex differences and to the increased prevalence of neuropsychiatric disorders. In this review, we highlight the recent findings of the effects of pre-, peri-, and postnatal exposure to the three well-studied EDCs (i.e., bisphenols (BPA, BPS, BPF, and BPAF), phthalates (DBP, BBP, DEHP, and DiPeP), and vinclozolin (VIN)) on developing brain and behavior across generations in experimental animals.

Keywords: BPA; BPAF; BPF; behavior; bps; endocrine-disrupting chemicals; phthalates; vinclozolin.

Figure 1

Intergenerational and transgenerational effects of endocrine-disrupting chemicals (EDCs): Embryonic exposure involves exposure of the F0 generation in female pregnancy, the F1 generation embryo (marked in red in the diagram), and the germline of the F2 generation. This intergenerational exposure indicates that the phenotypes of the F0-F2 generations may be due to direct exposure to EDCs. In embryonic exposure, this requires at least one F3 generation to be investigated, as this is the first generation not directly exposed to EDCs (transgenerational exposure). If exposure occurs in non-pregnant (F0) males or females (not represented in the diagram), there will be exposure of the germline of the F1 generation (intergenerational exposure). In this case, the F2 generation will represent the first generation not directly exposed to EDCs (transgenerational exposure).

Figure 2

Possible mechanisms of endocrine disrupting chemicals (EDCs) in brain and behavior abnormalities. Potential mediators (intracellular receptors, enzymes and different pathways, epigenetic mechanisms), the EDCs effects of which (brain and behavior abnormalities) have been demonstrated to be induced for each class of EDC, are linked by arrows to the EDC classes in parental (F0), there will be exposure of the germline of the F1 generation (intergenerational exposure). In this case, the F2 generation will represent the first generation not directly exposed to EDCs (transgenerational exposure). BPA, bisphenol A; ER, estrogen receptor; PPARγ, peroxisome proliferator-activated receptor gamma; AR, androgen receptor; ERK/MAPK pathway (extracellular signal-regulated kinase/mitogen-activated protein kinase), Ras, small guanosine triphosphatases (GTPases) from Ras superfamily;/Akt (protein kinase B)/TRHr, thyrotropin-releasing hormone receptor. + stimulate and – inhibit gene expression.