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Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-M\u00fcllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa161","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T19:19:10Z","timestamp":1595445550000},"page":"2813-2830","source":"Crossref","is-referenced-by-count":31,"title":["Erbb4 regulates the oocyte microenvironment during folliculogenesis"],"prefix":"10.1093","volume":"29","author":[{"given":"Ville","family":"Veikkolainen","sequence":"first","affiliation":[{"name":"Institute of Biomedicine and MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nsrein","family":"Ali","sequence":"additional","affiliation":[{"name":"Organogenesis Laboratory, Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Doroszko","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520 Turku, Finland"},{"name":"Department of Immunology Genetics and Pathology, Section for Neuro-oncology, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Kiviniemi","sequence":"additional","affiliation":[{"name":"Organogenesis Laboratory, Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Miinalainen","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Biocenter Oulu, University of Oulu, FI-90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claes","family":"Ohlsson","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Poutanen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520 Turku, Finland"},{"name":"Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafis","family":"Rahman","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Elenius","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine and MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland"},{"name":"Department of Oncology, Turku University Hospital, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo J","family":"Vainio","sequence":"additional","affiliation":[{"name":"Department of Immunology Genetics and Pathology, Section for Neuro-oncology, Uppsala University, 752 36 Uppsala, Sweden"},{"name":"InfoTech Oulu, Oulu University and Biobank Borealis of Northern Finland, Oulu University Hospital, University of Oulu, FI-90014 Oulu, FINLAND"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Naillat","sequence":"additional","affiliation":[{"name":"Organogenesis Laboratory, Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"2020101402144287300_ref1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3109\/00016341003623746","article-title":"Infertility, mental disorders and well-being\u2014a nationwide survey","volume":"89","author":"Klemetti","year":"2010","journal-title":"Acta Obstet. 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Endocrinol."},{"key":"2020101402144287300_ref23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1210\/me.2005-0185","article-title":"Role of the epidermal growth factor network in ovarian follicles","volume":"20","author":"Conti","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"2020101402144287300_ref24","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.4161\/cc.10.16.17194","article-title":"Function of ERBB4 is determined by alternative splicing","volume":"10","author":"Veikkolainen","year":"2011","journal-title":"Cell Cycle"},{"key":"2020101402144287300_ref25","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1126\/science.1065412","article-title":"Gamma-secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase","volume":"294","author":"Ni","year":"2001","journal-title":"Science"},{"key":"2020101402144287300_ref26","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1242\/dev.00715","article-title":"Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5","volume":"130","author":"Long","year":"2003","journal-title":"Development"},{"key":"2020101402144287300_ref27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/gene.10100","article-title":"Sertoli and granulosa cell-specific cre recombinase activity in transgenic mice","volume":"33","author":"Lecureuil","year":"2002","journal-title":"Genesis"},{"key":"2020101402144287300_ref28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","article-title":"Generalized lacZ expression with the ROSA26 cre reporter strain","volume":"21","author":"Soriano","year":"1999","journal-title":"Nat. Genet."},{"key":"2020101402144287300_ref29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mce.2003.09.006","article-title":"Genetic studies of the AMH\/MIS signaling pathway for m\u00fcllerian duct regression","volume":"211","author":"Jamin","year":"2003","journal-title":"Mol. Cell. Endocrinol."},{"key":"2020101402144287300_ref30","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1210\/en.2014-1890","article-title":"Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry","volume":"156","author":"Nilsson","year":"2015","journal-title":"Endocrinology"},{"key":"2020101402144287300_ref31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1530\/REP-10-0094","article-title":"Theca: the forgotten cell of the ovarian follicle","volume":"140","author":"Young","year":"2010","journal-title":"Reproduction"},{"key":"2020101402144287300_ref32","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1096\/fj.14-269035","article-title":"Hydroxysteroid (17\u03b2)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production","volume":"29","author":"Hakkarainen","year":"2015","journal-title":"FASEB J."},{"key":"2020101402144287300_ref33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-37766-2","article-title":"Three-dimensional organization of transzonal projections and other cytoplasmic extensions in the mouse ovarian follicle","volume":"9","author":"Baena","year":"2019","journal-title":"Sci. Rep."},{"key":"2020101402144287300_ref34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00418-006-0194-1","article-title":"Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis","volume":"126","author":"Berkholtz","year":"2006","journal-title":"Histochem. Cell Biol."},{"key":"2020101402144287300_ref35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/humupd\/dmv007","article-title":"Gap junction connexins in female reproductive organs: implications for women's reproductive health","volume":"21","author":"Winterhager","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"2020101402144287300_ref36","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1096\/fj.13-233247","article-title":"Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimullerian hormone expression during oocyte maturation in the female follicle","volume":"28","author":"Prunskaite-Hyyrylainen","year":"2014","journal-title":"FASEB J."},{"key":"2020101402144287300_ref37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/09513590.2017.1381838","article-title":"Relationship between serum anti-mullerian hormone and intrafollicular AMH levels in PCOS women","volume":"34","author":"Stracquadanio","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"2020101402144287300_ref38","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1093\/humrep\/deq212","article-title":"Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin","volume":"25","author":"Zamah","year":"2010","journal-title":"Hum. Reprod."},{"key":"2020101402144287300_ref39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrendo.2010.217","article-title":"Polycystic ovary syndrome: etiology, pathogenesis and diagnosis","volume":"7","author":"Goodarzi","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"2020101402144287300_ref40","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1210\/mend.13.6.0311","article-title":"Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries","volume":"13","author":"Nelson","year":"1999","journal-title":"Mol. Endocrinol."},{"key":"2020101402144287300_ref41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1477-7827-4-19","article-title":"Oocyte-granulosa cell interactions during mouse follicular development: regulation of kit ligand expression and its role in oocyte growth","volume":"4","author":"Thomas","year":"2006","journal-title":"Reprod. Biol. Endocrinol."},{"key":"2020101402144287300_ref42","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1530\/rep.0.1210647","article-title":"Cellular basis for paracrine regulation of ovarian follicle development","volume":"121","author":"Albertini","year":"2001","journal-title":"Reproduction"},{"key":"2020101402144287300_ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-02467-9","article-title":"Fatty acid binding protein 3 and transzonal projections are involved in lipid accumulation during in vitro maturation of bovine oocytes","volume":"7","author":"del Collado","year":"2017","journal-title":"Sci. Rep."},{"key":"2020101402144287300_ref44","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1095\/biolreprod63.3.723","article-title":"Dynamic changes of cumulus-oocyte cell communication during in vitro maturation of porcine oocytes","volume":"63","author":"Suzuki","year":"2000","journal-title":"Biol. Reprod."},{"key":"2020101402144287300_ref45","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1128\/MCB.01919-06","article-title":"Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation","volume":"27","author":"Hsieh","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"2020101402144287300_ref46","doi-asserted-by":"crossref","first-page":"e21574","DOI":"10.1371\/journal.pone.0021574","article-title":"Genetic dissection of epidermal growth factor receptor signaling during luteinizing hormone-induced oocyte maturation","volume":"6","author":"Hsieh","year":"2011","journal-title":"PLoS One"},{"key":"2020101402144287300_ref47","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1242\/jcs.196618","article-title":"ErbB1 and ErbB4 generate opposing signals regulating mesenchymal cell proliferation during valvulogenesis","volume":"130","author":"Iwamoto","year":"2017","journal-title":"J. Cell Sci."},{"key":"2020101402144287300_ref48","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1101\/gad.925702","article-title":"CD44 anchors the assembly of matrilysin\/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling","volume":"16","author":"Yu","year":"2002","journal-title":"Genes Dev."},{"key":"2020101402144287300_ref49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.fertnstert.2013.02.011","article-title":"Ontogeny of the ovary in polycystic ovary syndrome","volume":"100","author":"Dumesic","year":"2013","journal-title":"Fertil. Steril."},{"key":"2020101402144287300_ref50","first-page":"18","article-title":"All women with PCOS should be treated for insulin resistance","volume-title":"Fertil Steril","author":"Marshall","year":"2012"},{"key":"2020101402144287300_ref51","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1365-2265.2007.02764.x","article-title":"Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome","volume":"66","author":"Barber","year":"2007","journal-title":"Clin. Endocrinol."},{"key":"2020101402144287300_ref52","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/dvg.20352","article-title":"Conditional tamoxifen cre induced mutagenesis in the embryonic kidney in organ culture","volume":"45","author":"Jokela","year":"2007","journal-title":"Genesis"},{"key":"2020101402144287300_ref53","doi-asserted-by":"crossref","first-page":"e35538","DOI":"10.1371\/journal.pone.0035538","article-title":"Mouse estrous cycle identification tool and images","volume":"7","author":"Byers","year":"2012","journal-title":"PLoS One"},{"key":"2020101402144287300_ref54","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ydbio.2009.08.001","article-title":"Loss of inhibin alpha uncouples oocyte-granulosa cell dynamics and disrupts postnatal folliculogenesis","volume":"334","author":"Myers","year":"2009","journal-title":"Dev. Biol."},{"key":"2020101402144287300_ref55","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1210\/endo.132.4.8462469","article-title":"A supersensitive immunofluorometric assay for rat luteinizing hormone","volume":"132","author":"Haavisto","year":"1993","journal-title":"Endocrinology"},{"key":"2020101402144287300_ref56","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/hmg\/ddq027","article-title":"Wnt4\/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development","volume":"19","author":"Naillat","year":"2010","journal-title":"Hum. Mol. 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