Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization.

Background/aims: Hmgn2 is involved in regulating embryonic development, but its physiological function during embryo implantation and decidualization remains unknown.

Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to examine the expression of Hmgn2 in mouse uterus during the pre-implantation period and explore its function and regulatory mechanisms in epithelial adhesion junction and stromal cell proliferation and differentiation.

Results: Hmgn2 was primarily accumulated in uterine luminal epithelia on day 4 of pregnancy and subluminal stromal cells around the implanting blastocyst at implantation sites on day 5. Similar results were observed during delayed implantation and activation. Meanwhile, Hmgn2 expression was visualized in the decidua. In uterine epithelial cells, silencing of Hmgn2 by specific siRNA reduced the expression of adhesion molecules Cdh1, Cdh2 and Ctnnb1 and enhanced the expression of Muc1, whereas constitutive activation of Hmgn2 exhibited the opposite effects, suggesting a role for Hmgn2 in attachment reaction during embryo implantation. Estrogen stimulated the expression of Hmgn2 in uterine epithelia, but the stimulation was abrogated by ER antagonist ICI 182,780. Further analysis evidenced that attenuation of Hmgn2 might eliminate the regulation of estrogen on the expression of Cdh1, Cdh2 and Ctnnb1. In uterine stromal cells, progesterone induced the accumulation of Hmgn2 which advanced the expression of Prl8a2 and Prl3c1, two well-known differentiation markers for decidualization, but did not affect the proliferation of stromal cells. Knockdown of Hmgn2 blocked the progesterone-induced differentiation of uterine stromal cells. Moreover, Hmgn2 might serve as an intermediate to mediate the regulation of progesterone on Hand2.

Conclusion: Hmgn2 may play an important role during embryo implantation and decidualization.