Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway

TL;DR

Tryptophan boosts IGFBP1 in bovine endometrial cells via the TDO2-AHR pathway, which may affect uterine receptivity in cows.

Contribution

This study reveals a novel regulatory pathway involving tryptophan and kynurenine in modulating IGFBP1 expression in bovine endometrial cells.

Findings

Tryptophan increases IGFBP1 expression in bovine endometrial epithelial cells.

Tryptophan and kynurenine upregulate AHR, which is essential for IGFBP1 induction.

PGE2 enhances TDO2, AHR, and IGFBP1 expression in these cells.

Abstract

This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells.

Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1.

The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

The online version contains supplementary material available at 10.1186/s12917-024-04191-9.

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