Expression, regulation and function of Hmgn3 during decidualization in mice

• Hmgn3 was highly expressed in the decidua and decidualizing stromal cells.
• Hmgn3 could direct the expression of decidualization markers Prl8a2 and Prl3c1.
• Hmgn3 mediated the effects of Hoxa10 and cAMP on decidualization.
• Progesterone and cAMP induced the expression of Hmgn3 via Hoxa10.
• Hmgn3 acts downstream of Hoxa10 to direct the regulation of progesterone and cAMP on Hand2.

Although Hmgn3 is involved in the regulation of development and cellular differentiation, its physiological roles on decidualization are still unknown. Here we showed that Hmgn3 was highly expressed in the decidua and decidualizing stromal cells. Overexpression of Hmgn3 variants, Hmgn3a or Hmgn3b, enhanced the expression of decidualization markers Prl8a2 and Prl3c1, whereas inhibition of Hmgn3 reduced their expression. Hmgn3 could mediate the effects of Hoxa10 and cAMP on the expression of Prl8a2 and Prl3c1. Further study found that Hmgn3 directed the process of decidualization through influencing the expression of Hand2. Progesterone could induce the expression of Hmgn3 in the ovariectomized mouse uterus, uterine epithelial cells and stromal cells. Knockdown of Hoxa10 with siRNA alleviated the induction of progesterone and cAMP on Hmgn3 expression. Simultaneously, siRNA-mediated down-regulation of Hmgn3 in the uterine stromal cells could attenuate the effects of progesterone, cAMP and Hoxa10 on the expression of Hand2. Collectively, Hmgn3 may play an important role during mouse decidualization.