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.
Highlights
Neuregulins are members of epidermal growth factor family proteins, which play essential roles in embryogenesis and allow normal development of many internal organs and systems, including the nervous system and heart
Four types of neuregulins have been discovered [1]: (1) Neuregulin-1 occurring in various isoforms, playing a wide range functions in the living organism, first of all in the development of the nervous system and heart; (2) Neuregulin 2—inducing mainly the growth and development of epithelial, neuronal, and glial cells; (3) Neuregulin 3, which may act on receptor tyrosine-protein kinase ERBB-4 and is involved in pathological processes connected with schizophrenia and Hirschsprung’s disease; and (4) neuregulin 4, which is mainly expressed and secreted by brown adipocytes and may take participation in mechanisms during epithelial cell-related diseases, tumors, and glycolipid metabolic diseases
The number of neuregulin 1-like immunoreactive (NRG-1-LI) fibers was similar: In the uterine corpus—5.08 ± 0.43, in the right horn—2.93 ± 0.45, and in the left horn—3.08 ± 0.32. Both low and high doses of Bisphenol A (BPA) increased the number of NRG-1-positive nerves located in the muscular layer in all parts of the uterus studied, and the most visible changes were observed under high doses of the toxin
Summary
Neuregulins are members of epidermal growth factor family proteins, which play essential roles in embryogenesis and allow normal development of many internal organs and systems, including the nervous system and heart. The best known member of the neuregulin family is neuregulin 1 (NRG-1) This substance, described for the first time in 1992 [2], is a 44-kD glycoprotein, which contains amino acid sequence typical for epidermal growth factor and may interact with the ERBB receptors [3]. Regarding the peripheral nervous system [5], NRG-1 has been observed in dorsal root ganglia [8], neuronal cells, and nerves in the digestive tract [9] The functions of this substance within the peripheral nervous system are not fully explained, but it is known that NRG-1 could expect to show neuroprotective effects by the influence on survivability and regeneration of Schwann cells [10]. This substance is involved in regulatory processes connected with the activity of neuromediators and/or neuromodulators, receptors, and neuronal ion channels [5]
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