The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Abstract

Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

Bisphenol A (BPA)-Induced Changes in the Number of Serotonin-Positive Cells in the Mucosal Layer of Porcine Small Intestine—the Preliminary Studies

“…It should be emphasized that the lower dose of BPA used in this experiment (0.05 mg/kg body weight/day) is recommended as a tolerable daily intake (TDI) or reference dose in some countries [18]. The present study has indicated that such a dose is, however, not neutral for living organisms, in accordance with the previous studies in which the influence of this dose of BPA on the innervation of the GI tract and uterus was also observed [9,19].…”

The Influence of Bisphenol a on the Nitrergic Nervous Structures in the Domestic Porcine Uterus

“…In turn, the presence of nerves containing NO in various parts of the uterine wall confirms the multidirectional impact of this gaseous transmitter on the uterus, which is also known from previous publications, where the involvement of NO in uterine muscle activity, endometrial secretion, blood flow, and immunological processes has been reported [ 30 , 31 ]. The participation of nitrergic nerve fibers in various regulatory processes connected with the uterine activity may be also confirmed by a high degree of neurochemical diversification of such nerves and the co-localization of nNOS with a wide range of other neuronal substances, which was shown in the previous studies [ 10 , 11 , 21 ] and during the present investigation. It should be pointed out that substances noted in the present study in the uterine nitrergic nerves may be involved in various processes within the uterus, including the conduction of the sensory and pain stimuli, regulation of activity of the smooth muscles, as well as the influence on the endometrial secretion, blood flow in the uterine wall, immunological processes and the normal course of the estrus cycle [ 32 ].…”

“…Fragments of the uteri were subjected to standard single and double immunofluorescence technique according to the method described previously by Rytel [ 21 ], in which commercial antibodies against neuronal isoform of nitric oxide synthase (nNOS—used here as a marker of nitrergic neurons), vasoactive intestinal polypeptide (VIP), substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP), and cocaine- and amphetamine-regulated transcript (CART) were used ( Table 1 ). In short, the labeling procedure consisted of the following stages (all stages were performed at room temperature, stages 2, 3, and 4 were performed in the humid chamber): (1) drying the slices for 1 h; (2) incubation with blocking solution (10% normal goat serum, 0.1% bovine serum albumin, 0.01% NaN 3 , 0.25% Triton x-100 and 0.05% thimerosal in PBS) for 1 h; (3) incubation with one (single immunofluorescence technique) or a mixture of two (double immunofluorescence technique) primary antibodies for 20 h; (4) incubation with species-specific secondary antibodies marked with various fluorochromes ( Table 1 ); (5) treatment with buffered glycerol and coverage with coverslips.…”

“…Previous studies have reported that exposure to BPA leads to changes within the endometrium, which are manifested by fluctuations in the number of endometrial fibroblasts, inhibition of apoptotic reactions, and an increase in the thickness of this part of the uterine wall [ 10 , 11 ]. Moreover, BPA causes inhibition of the activity of the uterine muscular layer [ 21 ], distorts the estrus cycle, affects pregnancy [ 22 ], and disrupts embryo implantation in the uterus [ 23 ]. Some studies have reported the correlations between excessive exposure to BPA and diseases developing in the reproductive organs, including stromal polyps, endometriosis, and cervical cancer [ 24 ].…”

Bisphenol A (BPA) Affects the Enteric Nervous System in the Porcine Stomach

“…Earlier investigations have shown that BPA first affects the reproductive and nervous systems. In the reproductive system, exposure to BPA contributes to disturbances in the estrus cycle and puberty, as well as causing morphological changes in the uterus through hypertrophy of the mucosa and changes in nerves supplying this organ [ 6 ]. Some studies have reported connections between BPA and endometritis and cervical cancer [ 7 , 8 ].…”