The Neurochemical Characterization of Parasympathetic Nerve Fibers in the Porcine Uterine Wall Under Physiological Conditions and After Exposure to Bisphenol A (BPA)

Bisphenol A, a substance commonly used in plastic manufacturing, is relatively well known as an endocrine disruptor, which may bind to estrogen receptors and has multidirectional negative effects on both human and animal organisms. Previous studies have reported that BPA may act on the reproductive organs, but knowledge concerning BPA-induced changes within the nerves located in the uterine wall is extremely scant. The aim of this study was to investigate the impact of various doses of BPA on the parasympathetic nerves located in the corpus and horns of the uterus using a single and double immunofluorescence method. The obtained results have shown that BPA may change not only the expression of vesicular acetylcholine transporter (VAChT-a marker of parasympathetic nervous structures) in the uterine intramural nerve fibers, but also the degree of colocalization of this substance with other neuronal factors, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), and calcitonin gene-related peptide (CGRP). Moreover, BPA caused changes in the density of the overall populations of fibers immunoreactive to the particular neuropeptides mentioned above. The characteristics of the changes clearly depended on the part of the uterus, the neuronal factors studied, and the dosage of BPA. The mechanisms of the observed fluctuations are probably connected with the neurotoxic and/or pro-inflammatory activity of BPA. Moreover, the results have shown that even low doses of BPA are not neutral to living organisms. Changes in the neurochemical characterization of nerves supplying the uterine wall may be the first subclinical sign of intoxication with this substance.