Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol

Objective: Building upon prior research, our investigation focused on examining changes in gene expression of Connexins 37 and 43 (Cx) influenced by β2-adrenergic agents in cumulus cell cultures from women with polycystic ovarian syndrome (PCOS) and poor ovarian response (POR), all of whom were can...

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Main Authors: Farideh Zangeneh, Mohammad Mehdi Naghizadeh, Mina Jafarabadi, Masoumeh Dehghan, Maryam Bagheri
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2025-08-01
Series:Journal of Family and Reproductive Health
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Online Access:https://jfrh.tums.ac.ir/index.php/jfrh/article/view/2947
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author Farideh Zangeneh
Mohammad Mehdi Naghizadeh
Mina Jafarabadi
Masoumeh Dehghan
Maryam Bagheri
author_facet Farideh Zangeneh
Mohammad Mehdi Naghizadeh
Mina Jafarabadi
Masoumeh Dehghan
Maryam Bagheri
author_sort Farideh Zangeneh
collection DOAJ
description Objective: Building upon prior research, our investigation focused on examining changes in gene expression of Connexins 37 and 43 (Cx) influenced by β2-adrenergic agents in cumulus cell cultures from women with polycystic ovarian syndrome (PCOS) and poor ovarian response (POR), all of whom were candidates for in vitro fertilization (IVF). Materials and methods: This experimental study was conducted between April 2021 and November 2023, involving three groups: a control group (donated eggs) and two study groups (POR and PCO). All three groups received ovulation stimulation drugs. Following oocyte puncture, cumulus cells (CCs) were isolated and placed in a culture medium. After three passages, CCs were exposed to the ADR-β2 agonist isoproterenol and its antagonist propranolol (100nM for both drugs). RNA extraction was performed, and cDNA was synthesized. Real-time PCR was used to determine gene expression, and protein levels were measured through the Western blotting method. Results: The gene expression of Cx 37/43 was significantly reduced in all three groups (P<0.001). For women with PCO and POR, Isop notably decreased expressions (P<0.001), while Prop increased them (P<0.001). Western Blot results confirmed these findings. Conclusion: The findings of this in-vitro study suggest that the beta-2 adrenergic antagonist propranolol could upregulate gene expression of Cx37/43 in the cellular connections of CCs among infertile women. Consequently, propranolol may enhance communication between CCs and oocytes, facilitating the transfer of signalling messengers and other essential agents required for oocyte development. This novel discovery could have significant implications for oocyte growth and maturation, offering valuable perspectives on drug treatment and assisted reproductive technology. This novel discovery could have significant implications for oocyte growth and maturation, offering valuable perspectives on drug treatment and assisted reproductive technology.
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spelling doaj-art-c88b3134d08f45e3b3aceccae51ba2ab2025-08-20T02:58:34ZengTehran University of Medical SciencesJournal of Family and Reproductive Health1735-89491735-93922025-08-0119210.18502/jfrh.v19i2.19299Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of PropranololFarideh Zangeneh0Mohammad Mehdi Naghizadeh1Mina Jafarabadi2Masoumeh Dehghan3Maryam Bagheri4Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, IranNon-communicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, IranVali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, IranVali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, IranVali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Objective: Building upon prior research, our investigation focused on examining changes in gene expression of Connexins 37 and 43 (Cx) influenced by β2-adrenergic agents in cumulus cell cultures from women with polycystic ovarian syndrome (PCOS) and poor ovarian response (POR), all of whom were candidates for in vitro fertilization (IVF). Materials and methods: This experimental study was conducted between April 2021 and November 2023, involving three groups: a control group (donated eggs) and two study groups (POR and PCO). All three groups received ovulation stimulation drugs. Following oocyte puncture, cumulus cells (CCs) were isolated and placed in a culture medium. After three passages, CCs were exposed to the ADR-β2 agonist isoproterenol and its antagonist propranolol (100nM for both drugs). RNA extraction was performed, and cDNA was synthesized. Real-time PCR was used to determine gene expression, and protein levels were measured through the Western blotting method. Results: The gene expression of Cx 37/43 was significantly reduced in all three groups (P<0.001). For women with PCO and POR, Isop notably decreased expressions (P<0.001), while Prop increased them (P<0.001). Western Blot results confirmed these findings. Conclusion: The findings of this in-vitro study suggest that the beta-2 adrenergic antagonist propranolol could upregulate gene expression of Cx37/43 in the cellular connections of CCs among infertile women. Consequently, propranolol may enhance communication between CCs and oocytes, facilitating the transfer of signalling messengers and other essential agents required for oocyte development. This novel discovery could have significant implications for oocyte growth and maturation, offering valuable perspectives on drug treatment and assisted reproductive technology. This novel discovery could have significant implications for oocyte growth and maturation, offering valuable perspectives on drug treatment and assisted reproductive technology. https://jfrh.tums.ac.ir/index.php/jfrh/article/view/2947Cumulus CellsGap Junction Cx37/43 ExpressionsPolycystic Ovarian SyndromePoor Ovarian ResponseBeta 2 Adrenergic ReceptorsPropranolol
spellingShingle Farideh Zangeneh
Mohammad Mehdi Naghizadeh
Mina Jafarabadi
Masoumeh Dehghan
Maryam Bagheri
Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
Journal of Family and Reproductive Health
Cumulus Cells
Gap Junction Cx37/43 Expressions
Polycystic Ovarian Syndrome
Poor Ovarian Response
Beta 2 Adrenergic Receptors
Propranolol
title Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
title_full Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
title_fullStr Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
title_full_unstemmed Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
title_short Assessment of Gene Expression on the Gap Junction Connexin of Cumulus Cells on Infertile Women With Polycystic Ovary Syndrome and Poor Ovarian Response: The Novel Role of Propranolol
title_sort assessment of gene expression on the gap junction connexin of cumulus cells on infertile women with polycystic ovary syndrome and poor ovarian response the novel role of propranolol
topic Cumulus Cells
Gap Junction Cx37/43 Expressions
Polycystic Ovarian Syndrome
Poor Ovarian Response
Beta 2 Adrenergic Receptors
Propranolol
url https://jfrh.tums.ac.ir/index.php/jfrh/article/view/2947
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