Calcium-mediated aponecrosis plays a central role in the pathogenesis of estrogenic chemical-induced neurotoxicity.

Estrogen is traditionally associated with females but is also present in males, and influences aspects of brain chemistry and brain morphology in males, females and also during prenatal development. Humans as well as animals are additionally exposed to environmental products that mimic estrogen activity, also known as endocrine disrupters (EDCs). This hypothesis article investigates the role of estrogen (and also EDCs) in the brain and how it influences the Ca2+ pathway. Ca2+ and its movement in and out of the cell is an extremely important ion controlling normal cell physiology. Any dysfunction in the movement from outside to inside the cell or between organelles may have fundamentally negative effects and the disturbance may even lead to apoptosis and/or necrosis. Therefore we consider whether estrogen and EDCs may alter the Ca2+ physiology and whether these changes may be one of the main causes of interference in physiology that is seen when humans and animals are exposed to EDCs. We come to the conclusion that on a molecular level Ca2+ and Ca2+ fluxes ([Ca2+]i, endocrine disrupting chemicals, redox modulation, mitochondria and cytochrome c followed by apoptosis, necrosis or most likely aponecrosis may contribute to chemical-mediated developmental toxicity. Similarly, we hypothesize that calcium-mediated aponecrosis do not only play a central role in the pathophysiology of estrogenic chemical-induced neurotoxicity, but can contribute to chemical-mediated developmental toxicity in general, thereby affecting almost all cells and organs of the living organism.