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Abstract: SA-PO0942

L-Kynurenine Improves Embryo Implantation in Uninephrectomized Mice

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine

Authors

  • Wang, Yuye, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Zhou, Jiayi, The University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, United States
  • Maeda, Nobuyo, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Li, Feng, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
Background

Kidney plays a crucial role during the physiological adaptations of pregnancy, and kidney donors are at increased risk for developing pregnancy complications including preeclampsia. Dupont et al. recently demonstrated that wild type (WT) mice with impaired renal reserve (induced by uninephrectomy, UNx, a model mimicking kidney donation) develop the full spectrum of preeclampsia-like phenotypes during pregnancy, including hypertension, proteinuria, and increased fetal resorption. They also showed L-kynurenine rescues the phenotypes. However, whether preeclampsia-like phenotypes stem from earlier implantation defects and L-Kynurenine has any beneficial roles in this early stage of pregnancy remain unknown.

Methods

WT female mice (8-10 weeks old) underwent either UNx or sham surgery, followed by a two-week recovery period. Both groups were then mated with WT males. At 0.5 days post coitus (dpc), dams were randomly enrolled into vehicle (water) or L-Kynurenine (25 mg/L, w/v, via drinking water) groups. At 7.5 dpc, three-dimensional high-frequency ultrasonography were used to assess embryo development. Immediately after the procedure, dams from both groups were euthanized and uterine horns were isolated. The whole implantation site and maternal decidua were collected for examination of the markers of decidualization and angiogenesis by qRT-PCR and immunoassay.

Results

At 7.5 dpc, the volume of implantation sites was smaller in UNx dams compared to shams. The decidual vascular density at implantation sites was reduced in UNx dams. Immunostaining of VEGF (vascular endothelial growth factor) in endometrial region showed markedly different patterns. mRNA level of Vegfa is decreased in UNx dams. Bone Morphogenic Protein 2 (Bmp2, a marker of decidualization) also decreased. Additionally, the ectoplacental cone of UNx mice is distorted. L-kynurenine mitigated the detrimental changes observed in UNx dams.

Conclusion

Our data indicates that uninephrectomy delayed embryo development and impaired implantation. L-Kynurenine improves the embryo development and implantation in UNx dams.

Funding

  • Other NIH Support

Digital Object Identifier (DOI)