Lessons from In Utero and Postnatal Exposure to Pesticide DDT: Mechanisms of Chromaffin Cell Vulnerability and Altered Catecholamine Homeostasis

Dichlorodiphenyltrichloroethane (DDT) remains one of the most emblematic and enduring persistent organic pollutants of the 20th century. Although prohibited for agricultural use in most industrialized nations during the 1970s–1980s on the grounds of its persistence, bioaccumulation, and carcinogenicity, DDT was reintroduced by the World Health Organization in 2006 for indoor residual spraying against vector-borne diseases. Consequently, its environmental burden continues to be replenished rather than diminished. Biomonitoring surveys confirm the near-ubiquity of DDT residues in human populations. Low-dose human exposure to DDT occurs predominantly through contaminated food. Its main health risk is the ability of DDT to disrupt endocrine function. Numerous reports show negative effects of DDT on the reproductive system, the thyroid gland, and immune defense. Affection of the nervous system is sufficiently less studied. This article presents known mechanisms of endocrine disruption and summarizes current data on the disruption of the adrenal medulla by low-dose exposure to DDT. The review focuses on the three main aspects of chromaffin cell biology. The first one is endocrine function, including synthesis of catecholamines, secretory machinery and release of catecholamines into circulation. The second is embryonic and postnatal development of the adrenal medulla, and the third one is physiological cell renewal and maintenance of cell population, a novel enigmatic aspect of endocrine disruption. In conclusion, the authors present integrated mechanisms of disruption and indicate gaps in knowledge and directions for further investigations.