β‐Lactoglobulin affects the oxidative status and viability of equine endometrial progenitor cells via lncRNA‐mRNA‐miRNA regulatory associations

The β‐lactoglobulin (β‐LG) was previously characterized as a mild antioxidant modulating cell viability. However, its biological action regarding endometrial stromal cell cytophysiology and function has never been considered. In this study, we investigated the influence of β‐LG on the cellular status of equine endometrial progenitor cells under oxidative stress. The study showed that β‐LG decreased the intracellular accumulation of reactive oxygen species, simultaneously ameliorating cell viability and exerting an anti‐apoptotic effect. However, at the transcriptional level, the reduced mRNA expression of pro‐apoptotic factors (i.e. BAX and BAD) was accompanied by decreased expression of mRNA for anti‐apoptotic BCL‐2 and genes coding antioxidant enzymes (CAT, SOD‐1, GPx). Still, we have also noted the positive effect of β‐LG on the expression profile of transcripts involved in endometrial viability and receptivity, including ITGB1, ENPP3, TUNAR and miR‐19b‐3p. Finally, the expression of master factors of endometrial decidualization, namely prolactin and IGFBP1, was increased in response to β‐LG, while non‐coding RNAs (ncRNAs), that is lncRNA MALAT1 and miR‐200b‐3p, were upregulated. Our findings indicate a novel potential role of β‐LG as a molecule regulating endometrial tissue functionality, promoting viability and normalizing the oxidative status of endometrial progenitor cells. The possible mechanism of β‐LG action includes the activation of ncRNAs essential for tissue regeneration, such as lncRNA MALAT‐1/TUNAR and miR‐19b‐3p/miR‐200b‐3p.