Loss of high‐mobility group N5 contributes to the promotion of human endometrial stromal cell decidualization

PURPOSE: High‐mobility group N (HMGN) proteins are the only non‐histone proteins that specifically bind within the nucleosome between core histones and DNA. Among them, HMGN5 is one of the candidates that could participate in mouse endometrial decidualization; however, the specific role of HMGN5 remains to be clarified in human endometrial stromal cells (HESCs). METHODS: Primary HESCs were isolated from hysterectomy specimens and incubated with or without 8‐bromo‐cyclic adenosine monophosphate (8‐br‐cAMP) and medroxyprogesterone acetate (MPA). RESULTS: We demonstrated that HMGN5 expression in decidualized HESCs stimulated by 8‐br‐cAMP and MPA decreased significantly. The inhibition of HMGN5 expression by small interfering RNA (siRNA) induced the major decidual marker genes expression, including IGFBP1 (insulin‐like growth factor binding protein 1) and PRL (prolactin). In addition, microRNA‐542‐3p (miR‐542‐3p), which was identified as a regulatory miRNA of IGFBP1 during decidualization, was significantly suppressed by HMGN5 siRNA. However, the expression of HMGN5 was not alternated by miR‐542‐3p overexpression. CONCLUSIONS: These findings suggest that the down‐regulation of HMGN5 plays a role in the promotion of human endometrial stromal decidualization and acts upstream of miR‐542‐3p.