Nicotinamide ameliorates lipopolysaccharide-induced impairment of trophoblastic spheroid outgrowth in an in vitro implantation model
10.5653/cerm.2024.07472
- Author:
Wontae KIM
;
Inyoung KANG
;
Wonmo LEE
;
Jaewang LEE
;
Jin Hyun JUN
- Publication Type:Original Article
- From:Clinical and Experimental Reproductive Medicine
2026;53(2):137-146
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:Lipopolysaccharide (LPS), derived from various infectious bacteria in the uterus, interferes with communication between embryonic trophoblasts and endometrial cells, thereby inhibiting successful embryo implantation. This study aimed to investigate the effects of LPS and the anti-inflammatory compound nicotinamide (NAM) on early embryo implantation processes, focusing on the adhesion and outgrowth between trophoblast spheroids and endometrial cells.
Methods:We used JAr mixed JEG-3 (JmJ) spheroids, prepared by combining JAr and JEG-3 cells in a 1:1 ratio. Following treatment with LPS with or without NAM, the attachment and outgrowth of JmJ spheroids on endometrial epithelial cells (ECC-1) were assessed. Additionally, changes in the gene expression of inflammatory cytokines (chemokine (C-X-C motif) ligand 1 [CXCL1], interleukin 8 [IL-8], and IL-33) and cell adhesion molecules (integrin alpha-V [ITGαV], integrin beta 3 [ITGβ3], and integrin beta 5 [ITGβ5]) in ECC-1 cells following LPS and/or NAM treatment were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis.
Results:Decreased attachment rates and reduced outgrowth areas caused by LPS treatment were significantly restored by NAM. These restorative effects of NAM were associated with the modulation of inflammatory cytokines—specifically CXCL1 and IL-33, as shown by qRT-PCR—and expression of the cell adhesion molecule ITGβ3, as indicated by Western blot analysis.
Conclusion:Our study confirmed that LPS-induced endometrial infection may inhibit embryo implantation. NAM treatment ameliorated the detrimental effects of LPS by modulating the expression of inflammatory cytokines and adhesion molecules. Further studies are needed to explore the potential use of NAM as an effective additive to improve embryo implantation rates in human in vitro fertilization-embryo transfer programs.
