{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:10:29Z","timestamp":1773195029704,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014261","name":"National Institute for Healthcare Management Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Impaired renal reserve induced by unilateral nephrectomy (UNx) leads to the full-spectrum of phenotypes of preeclampsia (PE) in mice. L-kynurenine (a product of L-tryptophan metabolism) supplementation throughout the entire pregnancy rescues the PE-like phenotype in mice. However, whether UNx dams have endometrial decidualization deficiency during early pregnancy and whether L-kynurenine supplementation improve decidualization in UNx dams are not clear. While our prior study showed that nicotinamide (NAM) supplementation has beneficial effects on decidualization in mice with excess endothelin 1 (ET-1), whether NAM supplementation has a beneficial role in UNx dams is unknown. Here, we tested our hypothesis that UNx impairs uterine decidualization and L-kynurenine\/MAM treatment improves decidualization. We compared implantation sites between sham dams, UNx dams, and UNx dams treated with L-kynurenine or NAM. Implantation sites of UNx dams had lagged embryos with distorted ectoplacental cone and reduced vascular density in mesometrial regions of deciduae. The decidual expression of VEGF-A and markers of decidualization (e.g., BMP2, prolactin) was decreased in UNx dams. Both L-kynurenine and NAM corrected the abnormality present in maternal-embryo interface of UNx dams. In addition, the decidual expression of ET-1 and its type B receptor decreased in UNx dams, and L-kynurenine\/NAM increased their expression in the deciduae. Our results show that suppressed decidual ET-1\/EDNRB signaling could play a role in the poor decidualization (decreased BMP2\/prolactin) and angiogenesis (decreased VEGF) in UNx dams and both L-kynurenine and NAM have potential to improve embryo implantation and subsequent pregnancy outcomes.<\/jats:p>","DOI":"10.3389\/fphys.2026.1774244","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:30:35Z","timestamp":1773120635000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["L-kynurenine or nicotinamide supplementations mitigate uterine decidualization impairments during early pregnancy of uninephrectomized mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuye","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meitong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukako","family":"Kayashima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyo","family":"Maeda-Smithies","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.yjmcc.2022.03.007","article-title":"Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19","volume":"167","author":"Abraham","year":"2022","journal-title":"J. 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