Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration

Abstract

Methamphetamine (METH) can induce spermatogenesis impairment testicular apoptosis and abnormal sperm quality. It also promotes changes in the expression of receptors for sex hormones and neurotransmitters including GABA receptors in the testis. Proteomic assessment focusing on proteins involved in the calcium signalling pathway in the testis can facilitate diagnostic factors contributing to testicular and sperm functions especially those related to spermatogenesis and fertilisation. In this study we proposed to determine the localisation and differential expression of GABA A receptor alpha 1 subunit (GABA A-?1) in the spermatozoa of METH-administered rats. The differential proteomic profile of the testis was also observed by focusing on proteins in the KEGG pathways belonging to the calcium signalling pathway. There were 212 differentially expressed proteins in the rat testis based on the cut-off value of 1.2-fold change. Most of those proteins 13 proteins were classified in the calcium signalling pathway including 4 down-regulated and 9 up-regulated proteins. An immunolocalisation study of the GABA A-?1 receptor and calbindin revealed their localisation in the equatorial segment of the head in the rat spermatozoa. The expression of calbindin is also found in the middle piece of sperm. An increase in GABA A-?1 receptor in rat spermatozoa was correlated with an increase in abnormal sperm motility and morphology after methamphetamine exposure. Moreover calbindin expression in sperm decreased in METH-administered rats. All our findings demonstrate that METH influences intracellular calcium homeostasis by acting through the calcium signalling pathway-associated proteins. Moreover it might disrupt ion homeostasis in sperm through the GABA A-?1 receptor and calbindin triggering a change in intracellular calcium and chloride ions. These changes may cause abnormalities in spermatogenesis testicular apoptosis and sperm quality impairment. Copyright: ? 2023 Kaewman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use distribution and reproduction in any medium provided the original author and source are credited.