HYPOTHESIS AND THEORY article
Front. Physiol.
Sec. Reproductive and Mating Physiology
L-kynurenine or nicotinamide supplementations mitigate uterine decidualization impairments during early pregnancy of uninephrectomized mice
Feng Li
Yuye Wang
Qing Ma
Meitong Chen
Yukako Kayashima
Nobuyo Maeda-Smithies
University of North Carolina at Chapel Hill, Chapel Hill, United States
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Abstract
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.
Summary
Keywords
Endothelin-1, L-kynurenine, Mice, nicotinamide, Unilateral nephrectomy
Received
23 December 2025
Accepted
17 February 2026
Copyright
© 2026 Li, Wang, Ma, Chen, Kayashima and Maeda-Smithies. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Feng Li
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