Nuclear Receptor Co‐Regulator Krüppel‐like Factor 9 in Human Endometrial Stromal Cell Differentiation

The biological actions of ligand‐bound estrogen (E) and progesterone (P) receptors are dependent on coregulator partner proteins. We have identified Krüppel‐like Factor 9 (KLF9) as important for E and P actions in endometrial cells. Ablation of KLF9 in mice resulted in subfertility due partly to altered uterine sensitivity to E and P. KLF9 expression at peri‐implantation in mice was highest in endometrial stroma but was undetectable in decidua. To understand the significance of KLF loss with decidual formation, we used an immortalized human endometrial stromal cell line (HESC) responsive to E and P to evaluate the temporal expression of KLF9 during P‐induced decidualization. HESC treated with medium alone or with estradiol + medroxyprogesterone were analyzed for expression of KLF9 and differentiation marker genes by quantitative real‐time PCR. KLF9 transcripts began to rise above control levels at 6d, peaked at 8/9d, and decreased to 6d levels at 12d and 15d of treatment. Expression of the P‐responsive and KLF9‐regulated Hoxa10 gene coincided with that of KLF9 at 6d and 8/9d. By contrast, IGFBP1 transcript levels remained low until a ∼12‐fold increase at 15d, while that of prolactin increased at 8/9d and remained high thereafter. Results suggest that loss of KLF9 expression precedes stromal cell differentiation, suggestive of a preferential role for KLF9 in pre‐decidual stromal proliferation. (NIH‐HD21961)