{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:03:30Z","timestamp":1776261810935,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000325","name":"Wellbeing of Women","doi-asserted-by":"publisher","award":["RG1342"],"award-info":[{"award-number":["RG1342"]}],"id":[{"id":"10.13039\/501100000325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","award":["81671406"],"award-info":[{"award-number":["81671406"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","award":["31871412"],"award-info":[{"award-number":["31871412"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","award":["81702567"],"award-info":[{"award-number":["81702567"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Appropriate growth and development of the endometrium across the menstrual cycle is key for a woman\u2019s quality of life and reproductive well-being. Recurrent pregnancy loss (RPL) and heavy menstrual bleeding (HMB) affect a significant proportion of the female population worldwide. These endometrial pathologies have a significant impact on a woman\u2019s quality of life as well as placing a high economic burden on a country\u2019s health service. An underlying cause for both conditions is unknown in approximately 50% of cases. Previous research has demonstrated that aberrant endometrial vascular maturation is associated with both RPL and HMB, where it is increased in RPL but reduced in HMB. TGF\u03b21 is one of the key growth factors that regulate vascular maturation, by inducing phenotypic switching of vascular smooth muscle cells (VSMCs) from a synthetic phenotype to a more contractile one. Our previous data demonstrated an increase in TGF\u03b21 in the endometrium of RPL, while others have shown a decrease in women with HMB. However, TGF\u03b21 bioavailability is tightly controlled, and we therefore sought to perform an extensive immunohistochemical analysis of different components in the pathway in the endometrium of normal controls, women with HMB or RPL. In addition, two<jats:italic>in vitro<\/jats:italic>models were used to examine the role of TGF\u03b21 in endometrial vascular maturation and endothelial cell (EC):VSMC association. Taken all together, the immunohistochemical data suggest a decrease in bioavailability, receptor binding capacity, and signaling in the endometrium of women with HMB compared with controls. In contrast, there is an increase in the bioavailability of active TGF\u03b21 in the endometrium of women with RPL compared with controls. Endometrial explants cultured in TGF\u03b21 had an increase in the number of vessels associated with contractile VSMC markers, although the total number of vessels did not increase. In addition, TGF\u03b21 increased EC:VSMC association in an<jats:italic>in vitro<\/jats:italic>model. In conclusion, TGF\u03b21 is a key regulator of endometrial vascular maturation and could be considered as a therapeutic target for women suffering from HMB and\/or RPL.<\/jats:p>","DOI":"10.3389\/fcell.2021.640065","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T07:14:20Z","timestamp":1617952460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Transforming Growth Factor (TGF) \u03b2 and Endometrial Vascular Maturation"],"prefix":"10.3389","volume":"9","author":[{"given":"Qinsheng","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingqian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sourima Biswas","family":"Shivhare","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huomei","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith N.","family":"Bulmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara A.","family":"Innes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dharani K.","family":"Hapangama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gendie E.","family":"Lash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1093\/humrep\/14.12.3095","article-title":"Smooth muscle alpha actin and myosin heavy chain expression in the vascular smooth muscle cells surrounding human endometrial arterioles.","volume":"14","author":"Abberton","year":"","journal-title":"Hum. 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