Endocrine-Disrupting Chemicals and Hippocampal Development: The Role of Estrogen and Androgen Signaling

Abstract

Hormones are important regulators of key processes during fetal brain development. Thus, the developing brain is vulnerable to the action of chemicals that can interfere with endocrine signals. Epidemiological studies have pointed toward sexually dimorphic associations between neurodevelopmental outcomes, such as cognitive abilities, in children and prenatal exposure to endocrine disrupting chemicals (EDCs). This points toward disruption of sex steroid signalling in the development of neural structures underlying cognitive functions, such as the hippocampus, an essential mediator of learning and memory processes. Indeed, during development, the hippocampus is subjected to the organizational effects of estrogens and androgens, which influence hippocampal cell proliferation, differentiation, dendritic growth and synaptogenesis in the hippocampal fields of Cornu Ammonis and the dentate gyrus. These early organizational effects correlate with a sexual dimorphism in spatial cognition and are subject to exogenous chemical perturbations. This review summarises the current knowledge about the organizational effects of estrogens and androgens on the developing hippocampus and the evidence for hippocampal-dependent learning and memory perturbations induced by developmental exposure to EDCs. We conclude that, while it is clear that sex hormone signalling plays a significant role during hippocampal development, a complete picture at the molecular and cellular levels would be needed to establish causative links between the endocrine modes of action exerted by EDCs and the adverse outcomes these chemicals can induce at the organism level.

Neuroendocrine Disrupters

“…Lupu and her colleagues [3] provide a general review on how endogenous androgens and estrogens affect neuroplasticity, including neurogenesis, in the hippocampus, leading to consequences on learning and memory. Based on this fundamental biological knowledge, the authors review how several man-made chemicals, including bisphenols, phthalates, triclosan, and several pesticides (or crop-protection products) can alter the endocrine signaling, not only via interference with hormone receptors but also via an impact on the peripheral and local steroidogenesis.…”