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

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 i...

Full description

Bibliographic Details
Main Authors: Paweena Kaewman, Sutisa Nudmamud-Thanoi, Jitnapar Thongleart, Sawanya Charoenlappanit, Sittiruk Roytrakul, Samur Thanoi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812335/?tool=EBI
_version_ 1797959115736088576
author Paweena Kaewman
Sutisa Nudmamud-Thanoi
Jitnapar Thongleart
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
author_facet Paweena Kaewman
Sutisa Nudmamud-Thanoi
Jitnapar Thongleart
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
author_sort Paweena Kaewman
collection DOAJ
description 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-α1) 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-α1 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-α1 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-α1 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.
first_indexed 2024-04-11T00:28:06Z
format Article
id doaj.art-1fc1c9cf57fa4487bc39fb28c16b7c16
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-11T00:28:06Z
publishDate 2023-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-1fc1c9cf57fa4487bc39fb28c16b7c162023-01-08T05:31:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administrationPaweena KaewmanSutisa Nudmamud-ThanoiJitnapar ThongleartSawanya CharoenlappanitSittiruk RoytrakulSamur ThanoiMethamphetamine (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-α1) 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-α1 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-α1 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-α1 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812335/?tool=EBI
spellingShingle Paweena Kaewman
Sutisa Nudmamud-Thanoi
Jitnapar Thongleart
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
PLoS ONE
title Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
title_full Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
title_fullStr Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
title_full_unstemmed Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
title_short Differential protein expression of GABA A receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
title_sort differential protein expression of gaba a receptor alpha 1 subunit and calbindin in rat spermatozoa associated with proteomic analysis in testis following methamphetamine administration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812335/?tool=EBI
work_keys_str_mv AT paweenakaewman differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration
AT sutisanudmamudthanoi differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration
AT jitnaparthongleart differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration
AT sawanyacharoenlappanit differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration
AT sittirukroytrakul differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration
AT samurthanoi differentialproteinexpressionofgabaareceptoralpha1subunitandcalbindininratspermatozoaassociatedwithproteomicanalysisintestisfollowingmethamphetamineadministration