{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:16:50Z","timestamp":1791778610129,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2025-464"],"award-info":[{"award-number":["075-15-2025-464"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The study of ovarian biology is hampered by the lack of in vitro models that faithfully recapitulate the physiology of granulosa cells (GCs). Primary GCs have a limited lifespan, while most immortalized lines are tumor-derived and exhibit non-physiological hormonal responses. The purpose of this study was to develop and characterize a novel immortalized GC line with a stable, physiologically relevant phenotype. We immortalized primary murine GCs from early antral follicles using lentiviral vector to introduce human telomerase reverse transcriptase (hTERT) gene to create the IMG-A1 cell line. The line was extensively characterized using molecular (qRT-PCR, Western blot), cytogenetic (karyotyping), and functional (hormone stimulation, ELISA, proliferation assays) methods to assess its phenotype and responsiveness to gonadotropins and metabolic stressors. Exhibiting a non-transformed phenotype, IMG-A1 cells retain a stable karyotype and express the follicle-stimulating hormone receptor (FSHR) but not the luteinizing hormone\/chorionic gonadotropin receptor (LHCGR). Accordingly, they respond to FSH by upregulating steroidogenic genes like aromatase (Cyp19a1) but are unresponsive to LH\/hCG. Furthermore, the line exhibits physiologically relevant responses to hormonal stimulation, including a strong induction of aromatase by FSH and its synergistic upregulation in a hyperandrogenic and hyperinsulinemic milieu. The IMG-A1 cell line is a unique and robust model of early antral granulosa cells, offering a valuable new tool for studying FSH-dependent folliculogenesis, cellular aspects of ovarian pathophysiology, and drug discovery.<\/jats:p>","DOI":"10.3390\/cells14241940","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"1940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["IMG-A1: A Novel Immortalized Granulosa Cell Line for Investigating FSH-Dependent Folliculogenesis and Ovarian Pathophysiology"],"prefix":"10.3390","volume":"14","author":[{"given":"Nina M.","family":"Alyoshina","sequence":"first","affiliation":[{"name":"Department of Embryology, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia"},{"name":"Koltzov Institute of Developmental Biology, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-666X","authenticated-orcid":false,"given":"Evgenii S.","family":"Ruchko","sequence":"additional","affiliation":[{"name":"Koltzov Institute of Developmental Biology, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1475-0981","authenticated-orcid":false,"given":"Maria D.","family":"Tkachenko","sequence":"additional","affiliation":[{"name":"Department of Embryology, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia"},{"name":"Koltzov Institute of Developmental Biology, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria M.","family":"Potashnikova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail A.","family":"Lazarev","sequence":"additional","affiliation":[{"name":"Department of Embryology, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia O.","family":"Nikishina","sequence":"additional","affiliation":[{"name":"Koltzov Institute of Developmental Biology, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-6988","authenticated-orcid":false,"given":"Mariya S.","family":"Vildanova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4372-3338","authenticated-orcid":false,"given":"Ilia I.","family":"Zakharov","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-0848","authenticated-orcid":false,"given":"Viktoria V.","family":"Konduktorova","sequence":"additional","affiliation":[{"name":"Department of Embryology, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7461-4078","authenticated-orcid":false,"given":"Olga P.","family":"Kisurina-Evgenieva","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-9206","authenticated-orcid":false,"given":"Denis A.","family":"Nikishin","sequence":"additional","affiliation":[{"name":"Department of Embryology, Biological Faculty, Lomonosov Moscow State University, Moscow 119234, Russia"},{"name":"Koltzov Institute of Developmental Biology, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Malo, C., Oliv\u00e1n, S., Ochoa, I., and Shikanov, A. 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