Evaluation of expression patterns of different nicotinic acetylcholine receptor subunits in ovarian endometriosis in the search for promising new therapeutic targets for endometriosis

С А Леваков, Yu.A. Pertseva, М.Г. Кавиладзе, Т.А. Громова, T.A. Chernyshenko, Elena A. Gondarenko, D. V. Mazur, A. V. Mishanova, M. I. Shakhparonov, Kh.M. Mashtagova, Н. В. Антипова
In: Voprosy ginekologii, akušerstva i perinatologii · 2023 · vol. 22(5) , pp. 5–14 · doi:10.20953/1726-1678-2023-5-5-14 · W4391563795
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This study found that certain nicotinic acetylcholine receptor subunits are significantly upregulated in ovarian endometriosis samples compared to controls, with novel evidence for functional α4β2 receptors on endometriosis cells.

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This study evaluated the expression patterns of nicotinic acetylcholine receptor subunits in ovarian tissue from reproductive-aged women with endometriosis compared to a control group. Researchers utilized RNA isolation, real-time PCR, and patch-clamp techniques on primary cell cultures to assess both gene expression and functional activity. The results demonstrated significantly elevated levels of alpha-7, alpha-9, alpha-6, and alpha-4 subunits, while also identifying for the first time the presence and functionality of heteromeric alpha-4 beta-2 receptors in endometriosis cells. These findings suggest that these specific receptors could serve as promising therapeutic targets for suppressing pro-inflammatory cytokine production in ovarian endometriosis. This paper is centrally about endometriosis — specifically focusing on molecular mechanisms within ovarian lesions to identify new treatment avenues.

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Abstract

Objective. To study and evaluate the expression patterns of different subunits of nicotinic acetylcholine receptors (nAChRs) in reproductive-aged patients with ovarian endometriosis. Patients and methods. This study included 60 patients who were divided into two groups: group 1 – women with ovarian endometriosis, group 2 – control group. During surgical treatment, all patients underwent ovarian biopsy followed by RNA isolation, reverse transcription, real-time polymerase chain reaction, obtaining primary endometriosis cell cultures with further assessment of nAChR functional activity by the patch-clamp technique. Results. The study revealed a clinically significant expression of certain nAChR subunits, which was elevated specifically in biopsy samples obtained from endometriosis patients (α7, α9, α6, α4) compared to the control group. Furthermore, an increase in the expression of α4 and β2 subunits was detected for the first time, demonstrating the presence of heteromeric α4β2 receptors on endometriosis cells, the functionality of which was tested and confirmed by the patch-clamp technique. Conclusion. It was shown that the genes encoding these receptors are expressed at high levels, and the receptors themselves have good functional activity, which allows us to consider them as potential therapeutic targets for suppressing the production and secretion of pro-inflammatory cytokines in ovarian endometriosis. Key words: nicotine acetylcholine receptors, reverse transcription, real-time polymerase chain reaction, ovarian endometriosis, patch-clamp technique
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Evaluation of expression patterns of different nicotinic acetylcholine receptor subunits in ovarian endometriosis in the search for promising new therapeutic targets for endometriosis Sergey A. Levakov / Yulia A. Pertseva / Mariam G. Kaviladze / Tatyana A. Gromova / Tatyana A. Chernyshenko / Elena A. Gondarenko / Diana V. Mazur / Alexandra V. Mishanova / Mikhail I. Shakhraponov / Khava M. Mashtagova / Nadezhda V. Antipova / Objective. To study and evaluate the expression patterns of different subunits of nicotinic acetylcholine receptors (nAChRs) in reproductive-aged patients with ovarian endometriosis. Patients and methods. This study included 60 patients who were divided into two groups: group 1 – women with ovarian endometriosis, group 2 – control group. During surgical treatment, all patients underwent ovarian biopsy followed by RNA isolation, reverse transcription, real-time polymerase chain reaction, obtaining primary endometriosis cell cultures with further assessment of nAChR functional activity by the patch-clamp technique. Results. The study revealed a clinically significant expression of certain nAChR subunits, which was elevated specifically in biopsy samples obtained from endometriosis patients (α7, α9, α6, α4) compared to the control group. Furthermore, an increase in the expression of α4 and β2 subunits was detected for the first time, demonstrating the presence of heteromeric α4β2 receptors on endometriosis cells, the functionality of which was tested and confirmed by the patch-clamp technique. Conclusion. It was shown that the genes encoding these receptors are expressed at high levels, and the receptors themselves have good functional activity, which allows us to consider them as potential therapeutic targets for suppressing the production and secretion of pro-inflammatory cytokines in ovarian endometriosis. Key words: nicotine acetylcholine receptors, reverse transcription, real-time polymerase chain reaction, ovarian endometriosis, patch-clamp technique For citation: Levakov S.A., Pertseva Yu.A., Kaviladze M.G., Gromova T.A., Chernyshenko T.A., Gondarenko E.A., Mazur D.V., Mishanova A.V., Shakhparonov M.I., Mashtagova Kh.M., Antipova N.V. Evaluation of expression patterns of different nicotinic acetylcholine receptor subunits in ovarian endometriosis in the search for promising new therapeutic targets for endometriosis. Vopr. ginekol. akus. perinatol. (Gynecology, Obstetrics and Perinatology). 2023; 22(5): 5–14. (In Russian). DOI: 10.20953/1726-1678-2023-5-5-14

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