Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

Abstract

Polychlorinated biphenyls are among the most well-studied endocrine-disrupting chemicals (EDCs) for their neurobehavioral effects, especially neurodevelopment and cognitive performance. In addition, past research has demonstrated effects of PCBs on circulating hormones and associated changes in reproductive behaviors. This article will focus on recent advances that have been made in characterizing developmental PCB effects on reproductive function, broader social and affective behaviors, and the neuroendocrine mechanisms behind such changes. In general, PCBs seem to inhibit reproductive function by suppressing multiple aspects of the associated hypothalamic circuitry. Additionally, PCBs may also reduce motivation for social behaviors and induce depressive-like symptoms via overall reductions in dopaminergic and glutamatergic functions in the limbic system. However, more work with human-relevant exposure paradigms is needed to fully support these conclusions.

Figure 1

There are 209 different congeners of PCBs, and numbers and locations of chlorine atoms dictate structure and mechanism of action, as described above. Many studies use industrial mixtures of ~50 PCBs, called Aroclors. The degree of chlorination is indicated by the last two digits in each Aroclor name; for example; A1254 is 54% chlorine, with an average of 5 chlorines per molecules. Given that many of the receptor targets interact and that congeners (and their metabolites) exist in the environment in mixes, the physiological and behavioral outcomes of PCB exposure are always composites of multiple mechanisms interacting.

Figure 2

PCBs effects on neuroendocrine circuitry regulating reproductive physiology and sociosexual function. Brain regions and endocrine glands involved are shown as grey areas, labeled in all capital letters (STRI, striatum; HYP, hypothalamus; MID, midbrain; PIT, pituitary; GON, gonad) and containing appropriate neurotransmitters (Da, dopamine; Glu, glutamate; Kiss, kisspeptin), and hormones (Gnrh, Gonadotropin releasing hormone; Lh, leutinizing hormone; Fsh, follicle stimulating hormone; E, estradiol; P, progesterone; T, testosterone), within. Simplified functional connections between areas are shown with arrows; when possible a stimulatory (+) or inhibitory (-) effect on the downstream region is shown. All areas are responsive to gonadal hormones, as indicated by presence of ER and AR in dark and light blue cones, respectively. Overall effects of PCBs on neural systems (cell viability, synthesis, release, receptors, etc) are indicated by nearby red or green arrow, indicating an increase or decrease in function, respectively.