Veronika Kovaříková, Alexandra Špirková, Zuzana Šefčíková, Jozef Pisko, Laura Kalatová, Juraj Koppel, Dušan Fabian, Štefan Čikoš
{"title":"γ-氨基丁酸（GABA）可通过 GABAA 和 GABAB 受体影响着床前胚胎的生理过程。","authors":"Veronika Kovaříková, Alexandra Špirková, Zuzana Šefčíková, Jozef Pisko, Laura Kalatová, Juraj Koppel, Dušan Fabian, Štefan Čikoš","doi":"10.1002/rmb2.12528","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Several widely used substances (e.g., some therapeutics or food supplements) can act on gamma-aminobutyric acid (GABA) receptors, and we investigated whether the activation of these receptors could affect the preimplantation embryo.</p><p><strong>Methods: </strong>Transcripts of all GABA receptor subunits and selected proteins were examined using quantitative RT-PCR and immunohistochemistry. To analyze the effects of receptor activation, in vitro culture of mouse preimplantation embryos with natural and synthetic GABA receptor ligands was used.</p><p><strong>Results: </strong>We detected nine GABA receptor transcripts in mouse blastocysts and 14 GABA receptor transcripts in ovulated oocytes. The results of this study indicate that ionotropic GABA<sub>A</sub> receptors can be formed from α5, β3, and γ3 (or δ, π) subunits, GABA<sub>A-ρ</sub> receptors can be formed from ρ2 subunits and metabotropic GABA receptors can be formed from GABA<sub>B1b</sub> and GABA<sub>B2</sub> subunits in mouse blastocysts. Supplementing the culture medium with GABA at concentrations of 2-10 mM or with specific GABA<sub>A</sub> and GABA<sub>B</sub> receptor agonists (at concentrations of 10-100 μM) significantly increased the proportion of dead cells in blastocysts. The GABA-induced effects were prevented by pretreatment of embryos with GABA<sub>A</sub> and GABA<sub>B</sub> receptor antagonists.</p><p><strong>Conclusion: </strong>The results of this study indicate that GABA and synthetic GABA receptor ligands can negatively affect preimplantation embryos via GABA<sub>A</sub> and GABA<sub>B</sub> receptors.</p>","PeriodicalId":21116,"journal":{"name":"Reproductive Medicine and Biology","volume":"22 1","pages":"e12528"},"PeriodicalIF":2.7000,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/1a/RMB2-22-e12528.PMC10354355.pdf","citationCount":"0","resultStr":"{\"title\":\"Gamma-aminobutyric acid (GABA) can affect physiological processes in preimplantation embryos via GABA<sub>A</sub> and GABA<sub>B</sub> receptors.\",\"authors\":\"Veronika Kovaříková, Alexandra Špirková, Zuzana Šefčíková, Jozef Pisko, Laura Kalatová, Juraj Koppel, Dušan Fabian, Štefan Čikoš\",\"doi\":\"10.1002/rmb2.12528\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Several widely used substances (e.g., some therapeutics or food supplements) can act on gamma-aminobutyric acid (GABA) receptors, and we investigated whether the activation of these receptors could affect the preimplantation embryo.</p><p><strong>Methods: </strong>Transcripts of all GABA receptor subunits and selected proteins were examined using quantitative RT-PCR and immunohistochemistry. To analyze the effects of receptor activation, in vitro culture of mouse preimplantation embryos with natural and synthetic GABA receptor ligands was used.</p><p><strong>Results: </strong>We detected nine GABA receptor transcripts in mouse blastocysts and 14 GABA receptor transcripts in ovulated oocytes. The results of this study indicate that ionotropic GABA<sub>A</sub> receptors can be formed from α5, β3, and γ3 (or δ, π) subunits, GABA<sub>A-ρ</sub> receptors can be formed from ρ2 subunits and metabotropic GABA receptors can be formed from GABA<sub>B1b</sub> and GABA<sub>B2</sub> subunits in mouse blastocysts. Supplementing the culture medium with GABA at concentrations of 2-10 mM or with specific GABA<sub>A</sub> and GABA<sub>B</sub> receptor agonists (at concentrations of 10-100 μM) significantly increased the proportion of dead cells in blastocysts. The GABA-induced effects were prevented by pretreatment of embryos with GABA<sub>A</sub> and GABA<sub>B</sub> receptor antagonists.</p><p><strong>Conclusion: </strong>The results of this study indicate that GABA and synthetic GABA receptor ligands can negatively affect preimplantation embryos via GABA<sub>A</sub> and GABA<sub>B</sub> receptors.</p>\",\"PeriodicalId\":21116,\"journal\":{\"name\":\"Reproductive Medicine and Biology\",\"volume\":\"22 1\",\"pages\":\"e12528\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/1a/RMB2-22-e12528.PMC10354355.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/rmb2.12528\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/rmb2.12528","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Gamma-aminobutyric acid (GABA) can affect physiological processes in preimplantation embryos via GABAA and GABAB receptors.
Purpose: Several widely used substances (e.g., some therapeutics or food supplements) can act on gamma-aminobutyric acid (GABA) receptors, and we investigated whether the activation of these receptors could affect the preimplantation embryo.
Methods: Transcripts of all GABA receptor subunits and selected proteins were examined using quantitative RT-PCR and immunohistochemistry. To analyze the effects of receptor activation, in vitro culture of mouse preimplantation embryos with natural and synthetic GABA receptor ligands was used.
Results: We detected nine GABA receptor transcripts in mouse blastocysts and 14 GABA receptor transcripts in ovulated oocytes. The results of this study indicate that ionotropic GABAA receptors can be formed from α5, β3, and γ3 (or δ, π) subunits, GABAA-ρ receptors can be formed from ρ2 subunits and metabotropic GABA receptors can be formed from GABAB1b and GABAB2 subunits in mouse blastocysts. Supplementing the culture medium with GABA at concentrations of 2-10 mM or with specific GABAA and GABAB receptor agonists (at concentrations of 10-100 μM) significantly increased the proportion of dead cells in blastocysts. The GABA-induced effects were prevented by pretreatment of embryos with GABAA and GABAB receptor antagonists.
Conclusion: The results of this study indicate that GABA and synthetic GABA receptor ligands can negatively affect preimplantation embryos via GABAA and GABAB receptors.
期刊介绍：
Reproductive Medicine and Biology (RMB) is the official English journal of the Japan Society for Reproductive Medicine, the Japan Society of Fertilization and Implantation, the Japan Society of Andrology, and publishes original research articles that report new findings or concepts in all aspects of reproductive phenomena in all kinds of mammals. Papers in any of the following fields will be considered: andrology, endocrinology, oncology, immunology, genetics, function of gonads and genital tracts, erectile dysfunction, gametogenesis, function of accessory sex organs, fertilization, embryogenesis, embryo manipulation, pregnancy, implantation, ontogenesis, infectious disease, contraception, etc.
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