CSF1 positively regulates endometrial function and is associated with P38-MAPK pathway activation during early...

Embryo implantation is a complex biological process whose success depends on synchrony between a competent embryo and a receptive endometrium. In this study, we investigated the regulatory role of Colony-Stimulating Factor 1 (CSF1) in modulating endometrial function during early pregnancy in goats. CSF1 expression was significantly upregulated during early gestation. Functionally, CSF1 overexpression in goat endometrial epithelial cells (gEECs) markedly enhanced the expression of epithelial-mesenchymal transition (EMT) markers, including Vimentin and N-cadherin. In hormone-treated gEECs, CSF1 regulated RSAD2 expression but did not significantly affect ISG15 or CXCL10. Conversely, CSF1 silencing attenuated these effects. Transcriptomic analysis implicated the P38-MAPK signaling pathway as a downstream mediator of CSF1-induced endometrial receptivity. Mechanistically, CSF1 increased P38 phosphorylation and partial EMT marker expression. Pharmacological activation of P38 using HY-B1204 rescued the downregulation of N-cadherin induced by CSF1 silencing, although Vimentin expression was not significantly restored. Collectively, these findings demonstrate that CSF1 is associated with activation of the P38-MAPK pathway, thereby regulating molecular characteristics of endometrial receptivity during early implantation in goats and providing new insights into CSF1-mediated mechanisms in ruminant reproduction.