{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:27:06Z","timestamp":1792189626923,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["110-CGH-FJU-05"],"award-info":[{"award-number":["110-CGH-FJU-05"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["MOST-111-2314-B-281-009"],"award-info":[{"award-number":["MOST-111-2314-B-281-009"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["110-CGH-FJU-05"],"award-info":[{"award-number":["110-CGH-FJU-05"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST-111-2314-B-281-009"],"award-info":[{"award-number":["MOST-111-2314-B-281-009"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor \u03b2 (TGF\u03b2), TNF-\u03b1, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGF\u03b23 in regulating TX generation in human ovarian follicular GCs. TGF\u03b23 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 \u00b1 12.38 and 112.55 \u00b1 14.82 pg\/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGF\u03b23 induced TX generation\/secretion and the converting enzyme-COX-2 protein\/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGF\u03b2RI and Smad2\/3 signaling was mainly required for COX-2 induction, ERK1\/2 appeared to regulate TX secretion. The participation of Smad2\/3 and COX-2 in TGF\u03b23-induced TX generation\/secretion could be further supported by the observations that Smad2\/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGF\u03b23. Taken together, the results presented here first demonstrated that FF TGF\u03b23 levels differ significantly in IVF patients\u2019 large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGF\u03b23 can provoke TX generation by induction of COX-2 mRNA\/protein via a TGF\u03b2R-related canonical Smad2\/3 signaling pathway, and TX secretion possibly by ERK1\/2. These imply that TGF\u03b23 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation.<\/jats:p>","DOI":"10.3390\/ijms25105558","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T08:20:31Z","timestamp":1716193231000},"page":"5558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Presence of TGF\u03b23 in Human Ovarian Intrafollicular Fluid and Its Involvement in Thromboxane Generation in Follicular Granulosa Cells through a Canonical TGF\u03b2RI, Smad2\/3 Signaling Pathway and COX-2 Induction"],"prefix":"10.3390","volume":"25","author":[{"given":"Tsung-Hsuan","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Cathay General Hospital, No. 280, Renai Rd. Daan Dist., Taipei 10693, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-7898","authenticated-orcid":false,"given":"Hsuan-Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Pharmaceutic Biotechnology, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pi-Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-5030","authenticated-orcid":false,"given":"Wen-Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan"},{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref_1","first-page":"137","article-title":"Comparison of different stimulation protocols used in in vitro fertilization: A review","volume":"3","author":"Shrestha","year":"2015","journal-title":"Ann. 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