Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep
BackgroundSMYD3 is a histone methyltransferase known for its dual role in modifying both histone and non-histone proteins. Despite its established involvement in somatic cell function and oncogenesis, its role in mammalian oogenesis and early embryonic development remains unclear. This study aimed t...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| author | Chiara Camerano Spelta Rapini Alessia Peserico Chiara Di Berardino Giulia Capacchietti Camila Rojo-Fleming Andrada-Ioana Damian-Buda Irem Unalan Aldo Roberto Boccaccini Valentina Grossi Mauro Mattioli Barbara Barboni |
| author_facet | Chiara Camerano Spelta Rapini Alessia Peserico Chiara Di Berardino Giulia Capacchietti Camila Rojo-Fleming Andrada-Ioana Damian-Buda Irem Unalan Aldo Roberto Boccaccini Valentina Grossi Mauro Mattioli Barbara Barboni |
| author_sort | Chiara Camerano Spelta Rapini |
| collection | DOAJ |
| description | BackgroundSMYD3 is a histone methyltransferase known for its dual role in modifying both histone and non-histone proteins. Despite its established involvement in somatic cell function and oncogenesis, its role in mammalian oogenesis and early embryonic development remains unclear. This study aimed to elucidate the function of SMYD3 in regulating oocyte meiotic progression and developmental competence using sheep as a mono-ovulatory model.ResultsUtilizing a 3D follicle-enclosed in vitro maturation (FEO-IVM) system, the study examined the impact of SMYD3 inhibition on oocyte maturation within Early Antral follicles In the absence of human chorionic gonadotropin oocytes remained arrested at the germinal vesicle (GV) stage. Interestingly, treatment with a SMYD3 inhibitor (iSMYD3) alone prompted germinal vesicle breakdown (GVBD) in 67% of oocytes; however, progression to the metaphase II (MII) stage was achieved only when iSMYD3 was combined with hCG, resulting in a 73% maturation rate. Despite this, MII oocytes from the iSMYD3 group exhibited compromised developmental competence, as evidenced by the failure of parthenogenetic embryos to progress beyond the 8-cell stage, contrasting with a 29% success rate in the hCG-only group. At the molecular level, SMYD3 inhibition led to sustained activation of CDC25A within oocytes, facilitating GVBD but impeding the MI-MII transition due to the absence of CDC25A degradation. Moreover, iSMYD3 failed to activate the MAPK1/3 and PDE5A pathways in the somatic compartment, unlike hCG treatment, indicating distinct signaling mechanisms. Additionally, hCG rapidly downregulated SMYD3 expression in follicular walls and cumulus cells, a process independent of meiotic progression but essential for metabolic decoupling between oocytes and cumulus cells. SMYD3 inhibition disrupted this decoupling by preventing hCG-induced gap junction closure, thereby maintaining prolonged intercellular communication.ConclusionSMYD3 is identified as a key modulator of oocyte maturation, orchestrating meiotic progression through CDC25A regulation and interacting with hCG-driven somatic signaling. These findings highlight SMYD3 as a critical determinant of late oogenesis and a potential target for enhancing oocyte competence in assisted reproductive technologies |
| format | Article |
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| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-f4a59cbbfd144bbfb956f96e1a5e7ef62025-08-20T02:20:41ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16259141625914Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheepChiara Camerano Spelta Rapini0Alessia Peserico1Chiara Di Berardino2Giulia Capacchietti3Camila Rojo-Fleming4Andrada-Ioana Damian-Buda5Irem Unalan6Aldo Roberto Boccaccini7Valentina Grossi8Mauro Mattioli9Barbara Barboni10Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, GermanyDepartment of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, GermanyMedical Genetics, National Institute of Gastroenterology, IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte (Ba), ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, ItalyBackgroundSMYD3 is a histone methyltransferase known for its dual role in modifying both histone and non-histone proteins. Despite its established involvement in somatic cell function and oncogenesis, its role in mammalian oogenesis and early embryonic development remains unclear. This study aimed to elucidate the function of SMYD3 in regulating oocyte meiotic progression and developmental competence using sheep as a mono-ovulatory model.ResultsUtilizing a 3D follicle-enclosed in vitro maturation (FEO-IVM) system, the study examined the impact of SMYD3 inhibition on oocyte maturation within Early Antral follicles In the absence of human chorionic gonadotropin oocytes remained arrested at the germinal vesicle (GV) stage. Interestingly, treatment with a SMYD3 inhibitor (iSMYD3) alone prompted germinal vesicle breakdown (GVBD) in 67% of oocytes; however, progression to the metaphase II (MII) stage was achieved only when iSMYD3 was combined with hCG, resulting in a 73% maturation rate. Despite this, MII oocytes from the iSMYD3 group exhibited compromised developmental competence, as evidenced by the failure of parthenogenetic embryos to progress beyond the 8-cell stage, contrasting with a 29% success rate in the hCG-only group. At the molecular level, SMYD3 inhibition led to sustained activation of CDC25A within oocytes, facilitating GVBD but impeding the MI-MII transition due to the absence of CDC25A degradation. Moreover, iSMYD3 failed to activate the MAPK1/3 and PDE5A pathways in the somatic compartment, unlike hCG treatment, indicating distinct signaling mechanisms. Additionally, hCG rapidly downregulated SMYD3 expression in follicular walls and cumulus cells, a process independent of meiotic progression but essential for metabolic decoupling between oocytes and cumulus cells. SMYD3 inhibition disrupted this decoupling by preventing hCG-induced gap junction closure, thereby maintaining prolonged intercellular communication.ConclusionSMYD3 is identified as a key modulator of oocyte maturation, orchestrating meiotic progression through CDC25A regulation and interacting with hCG-driven somatic signaling. These findings highlight SMYD3 as a critical determinant of late oogenesis and a potential target for enhancing oocyte competence in assisted reproductive technologieshttps://www.frontiersin.org/articles/10.3389/fcell.2025.1625914/fullSMYD3follicle-enclosed oocyte in vitro maturation (FEO-IVM)ovine oocyte competencecumulus-oocyte metabolic couplinghCG-dependent signaling pathways |
| spellingShingle | Chiara Camerano Spelta Rapini Alessia Peserico Chiara Di Berardino Giulia Capacchietti Camila Rojo-Fleming Andrada-Ioana Damian-Buda Irem Unalan Aldo Roberto Boccaccini Valentina Grossi Mauro Mattioli Barbara Barboni Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep Frontiers in Cell and Developmental Biology SMYD3 follicle-enclosed oocyte in vitro maturation (FEO-IVM) ovine oocyte competence cumulus-oocyte metabolic coupling hCG-dependent signaling pathways |
| title | Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep |
| title_full | Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep |
| title_fullStr | Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep |
| title_full_unstemmed | Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep |
| title_short | Investigating SMYD3 role during oocyte maturation in a 3D follicle-enclosed oocyte in vitro model in sheep |
| title_sort | investigating smyd3 role during oocyte maturation in a 3d follicle enclosed oocyte in vitro model in sheep |
| topic | SMYD3 follicle-enclosed oocyte in vitro maturation (FEO-IVM) ovine oocyte competence cumulus-oocyte metabolic coupling hCG-dependent signaling pathways |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1625914/full |
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