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Cell Dev. Biol."],"abstract":"<jats:p>Neurotrophin-4 (NT-4), a granulosa cell-derived factor and a member of the neurotrophin family, is known to promote follicular development and oocyte maturation in mammals. However, the physiological and functional roles of NT-4 in porcine ovarian development are not yet known. The aim of this study was to investigate the physiological role of NT-4-related signaling in the <jats:italic>in vitro<\/jats:italic> maturation (IVM) of porcine cumulus\u2013oocyte complexes (COCs). The NT-4 protein and its receptors were detected in matured porcine COCs <jats:italic>via<\/jats:italic> immunofluorescence analysis. NT-4 was shown to promote the maturation of COCs by upregulating <jats:italic>NFKB1<\/jats:italic> transcription via the neurotrophin\/p75<jats:sup>NTR<\/jats:sup> signaling pathway. Notably, the mRNA expression levels of the oocyte-secreted factors <jats:italic>GDF9<\/jats:italic> and <jats:italic>BMP15<\/jats:italic>, sperm\u2013oocyte interaction regulator <jats:italic>CD9<\/jats:italic>, and DNA methylase <jats:italic>DNMT3A<\/jats:italic> were significantly upregulated in NT-4-treated than in untreated porcine oocytes. Concurrently, there were no significant differences in the levels of total and phosphorylated epidermal growth factor receptor and p38 mitogen-activated protein kinase between NT-4-treated and untreated cumulus cells (CCs); however, the level of phosphorylated ERK1\/2 was significantly higher in NT-4-treated CCs. Both total and phosphorylated ERK1\/2 levels were significantly higher in NT-4-treated than in untreated oocytes. In addition, NT-4 improved subsequent embryonic development after <jats:italic>in vitro<\/jats:italic> fertilization and somatic cell nuclear transfer. Therefore, the physiological and functional roles of NT-4 in porcine ovarian development include the promotion of oocyte maturation, CC expansion, and ERK1\/2 phosphorylation in porcine COCs during IVM.<\/jats:p>","DOI":"10.3389\/fcell.2022.908992","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T08:17:16Z","timestamp":1657268236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Physiological and Functional Roles of Neurotrophin-4 During In Vitro Maturation of Porcine Cumulus\u2013Oocyte Complexes"],"prefix":"10.3389","volume":"10","author":[{"given":"Mirae","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Ung","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchul David","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyerin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjin","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabsang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hwan","family":"Hyun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-21644-z","article-title":"Epidermal Growth Factor Receptor Signaling Uncouples Germ Cells from the Somatic Follicular Compartment at Ovulation","volume":"12","author":"Abbassi","year":"2021","journal-title":"Nat. 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