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

Abstract

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.

The Endocrine Disruptor Bisphenol A (BPA) Affects the Enteric Neurons Immunoreactive to Neuregulin 1 (NRG1) in the Enteric Nervous System of the Porcine Large Intestine

“…Admittedly, in 2015 the EFSA temporarily reduced the TDI for BPA to 4 µg/kg b.w./day [ 102 ] making the final decision dependent on further studies, but in many countries the TDI or the reference dose for BPA was set at 0.05 mg/kg b.w./day [ 103 ]. The results obtained during the present study, together with previous studies in which the influence of BPA at the dose of 0.05 mg/kg b.w./day on the neurochemical characterization of neurons supplying the uterus, liver and GI tract was reported [ 60 , 89 , 90 ], indicate that such doses are not neutral for a living organism. Of course, it should be underlined that the dose of 0.05 mg/kg b.w./day is significantly higher than the doses on which people are exposed in everyday life.…”

“…The knowledge of the influence of BPA on the peripheral nervous system is more limited than on the central nervous system. It is known that BPA inhibits the voltage-gated sodium channels in dorsal root ganglia and may change the neurochemical characterization in autonomic nervous structures supplying various internal organs [ 60 , 88 , 89 , 90 , 91 ]. The decrease in total number of neurons noted in the present study under the impact of BPA also confirms neurotoxic properties of this substance.…”

Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

“…However, in the uterus, sympathetic fibers are the most abundant and they exist in all layers of the uterine wall, and in the MYO they supply myocytes and blood vessels. The crucial neurotransmitter of this part of the nervous system is noradrenaline (NA) 15 , 16 which (similarly as other catecholamines) exerts biological effects via adrenergic receptors (ARs). Taking into account both localization and functional activities, ARs are classified into α and β types.…”

Actions of Bisphenol A on Different Feto-Maternal Compartments Contributing to Preterm Birth

“…Curiously, bisphenol has been found to decrease the myometrial contractions in various experiments, despite increasing OXTR and OXT expression [ 102 , 103 ]. This dose-dependent decrease in amplitude and frequency of contractions has been suggested to operate via (1)a nitric oxide-involving pathway, and (2)a vesicular acetylcholine transporter (VACht)-mediated pathway; however, these mouse- and porcine-related uterine changes remain to be replicated in human cells [ 104 , 105 , 106 ].…”