Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival
Summary: Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220310099 |
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doaj-cabed82ba6b444c2afda83fbfa6c92c3 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Livio Casarini Clara Lazzaretti Elia Paradiso Silvia Limoncella Laura Riccetti Samantha Sperduti Beatrice Melli Serena Marcozzi Claudia Anzivino Niamh S. Sayers Jakub Czapinski Giulia Brigante Francesco Potì Antonio La Marca Francesco De Pascali Eric Reiter Angela Falbo Jessica Daolio Maria Teresa Villani Monica Lispi Giovanna Orlando Francesca G. Klinger Francesca Fanelli Adolfo Rivero-Müller Aylin C. Hanyaloglu Manuela Simoni |
| spellingShingle |
Livio Casarini Clara Lazzaretti Elia Paradiso Silvia Limoncella Laura Riccetti Samantha Sperduti Beatrice Melli Serena Marcozzi Claudia Anzivino Niamh S. Sayers Jakub Czapinski Giulia Brigante Francesco Potì Antonio La Marca Francesco De Pascali Eric Reiter Angela Falbo Jessica Daolio Maria Teresa Villani Monica Lispi Giovanna Orlando Francesca G. Klinger Francesca Fanelli Adolfo Rivero-Müller Aylin C. Hanyaloglu Manuela Simoni Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival iScience Molecular Biology Female Reproductive Endocrinology Endocrine Regulation |
| author_facet |
Livio Casarini Clara Lazzaretti Elia Paradiso Silvia Limoncella Laura Riccetti Samantha Sperduti Beatrice Melli Serena Marcozzi Claudia Anzivino Niamh S. Sayers Jakub Czapinski Giulia Brigante Francesco Potì Antonio La Marca Francesco De Pascali Eric Reiter Angela Falbo Jessica Daolio Maria Teresa Villani Monica Lispi Giovanna Orlando Francesca G. Klinger Francesca Fanelli Adolfo Rivero-Müller Aylin C. Hanyaloglu Manuela Simoni |
| author_sort |
Livio Casarini |
| title |
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival |
| title_short |
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival |
| title_full |
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival |
| title_fullStr |
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival |
| title_full_unstemmed |
Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival |
| title_sort |
membrane estrogen receptor (gper) and follicle-stimulating hormone receptor (fshr) heteromeric complexes promote human ovarian follicle survival |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2020-12-01 |
| description |
Summary: Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gβγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation. |
| topic |
Molecular Biology Female Reproductive Endocrinology Endocrine Regulation |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004220310099 |
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doaj-cabed82ba6b444c2afda83fbfa6c92c32020-12-19T05:09:59ZengElsevieriScience2589-00422020-12-012312101812Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle SurvivalLivio Casarini0Clara Lazzaretti1Elia Paradiso2Silvia Limoncella3Laura Riccetti4Samantha Sperduti5Beatrice Melli6Serena Marcozzi7Claudia Anzivino8Niamh S. Sayers9Jakub Czapinski10Giulia Brigante11Francesco Potì12Antonio La Marca13Francesco De Pascali14Eric Reiter15Angela Falbo16Jessica Daolio17Maria Teresa Villani18Monica Lispi19Giovanna Orlando20Francesca G. Klinger21Francesca Fanelli22Adolfo Rivero-Müller23Aylin C. Hanyaloglu24Manuela Simoni25Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy; Corresponding authorUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; International PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; International PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; Center for Genomic Research, University of Modena and Reggio Emilia, Modena, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, ItalyHistology and Embryology Section, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalyUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, ItalyInstitute of Reproductive and Developmental Biology, Imperial College London, London, UKDepartment of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland; Postgraduate School of Molecular Medicine, Warsaw, PolandUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyDepartment of Medicine and Surgery, Unit of Neurosciences, University of Parma, Parma, ItalyMother-Infant Department, University of Modena and Reggio Emilia, Modena, Italy; Clinica EUGIN, Modena, ItalyPRC, INRAE, CNRS, IFCE, Université de Tours, Nouzilly, FrancePRC, INRAE, CNRS, IFCE, Université de Tours, Nouzilly, FranceDepartment of Obstetrics and Gynaecology, Fertility Center, ASMN. Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Modena, ItalyDepartment of Obstetrics and Gynaecology, Fertility Center, ASMN. Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Modena, ItalyDepartment of Obstetrics and Gynaecology, Fertility Center, ASMN. Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Modena, ItalyInternational PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, Italy; Global Medical Affair, Merck KGaA, Darmstadt, GermanyMedical Affair, Merck Serono SpA, Rome, ItalyHistology and Embryology Section, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, ItalyDepartment of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, PolandInstitute of Reproductive and Developmental Biology, Imperial College London, London, UKUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Ospedale Civile Sant’Agostino-Estense, Via P. Giardini 1355, 41126 Modena, Italy; Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy; Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy; PRC, INRAE, CNRS, IFCE, Université de Tours, Nouzilly, FranceSummary: Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gβγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.http://www.sciencedirect.com/science/article/pii/S2589004220310099Molecular BiologyFemale Reproductive EndocrinologyEndocrine Regulation |