Ovarian steroids modulate mRNA expression of ECM associated genes and collagen deposition induced by TGF β1 in equine...

Equine endometrosis is a major cause of infertility in mares and is characterized by degenerative, functional and fibrotic changes in the endometrium with increased collagen (COL) deposition. Transforming growth factor (TGF)-β1 is one of the major pro-fibrotic factors involved in the excessive deposition of extracellular matrix (ECM) components in the equine endometrium. It has been demonstrated that ovarian steroids, specifically 17β-estradiol (E2) and progesterone (P4), not only regulate the cyclicity of the estrous cycle, but also have been implicated as anti- or pro-fibrotic factors. This study aimed to evaluate (i) the effect of E2 and P4 on the expression of ECM-associated genes including COL1A1, COL3A1, matrix metalloproteases (MMPs): MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13, and tissue inhibitors of MMPs (TIMPs): TIMP-1 and TIMP-2 in equine endometrial fibroblasts, and (ii) the effect of ovarian steroids on TGF-β1-induced COL1 expression in equine endometrial explants from the follicular and mid-luteal phases of the estrous cycle. The mRNA expression of ECM-associated genes in endometrial fibroblasts and TGF-β1-induced COL1 expression in endometrial explants was modulated by ovarian steroids, with variations depending on the type of steroid and the duration of treatment. Moreover, P4 decreased TGF-β1-induced COL1 protein abundance in the mid-luteal phase of the estrous cycle after 48 h (p < 0.05). The results of our study indicate that during the estrous cycle, the ovarian steroids E2 or P4 may act directly on endometrial fibroblasts, thereby affecting the expression of genes involved in tissue remodeling, namely MMPs and TIMPs. Furthermore, P4 appears to affect not only the ECM-associated genes in endometrial fibroblasts, but also to attenuate the pro-fibrotic action of TGF-β1 in the mid-luteal stage of the estrous cycle.