Requirement of heart and neural crest derivatives expressed transcript 2 during decidualization of human endometrial stromal cells in vitro

Progestin-induced heart and neural crest derivatives–expressed transcript 2 plays a key role in the regulation of human decidualization.

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Hisayuu Shindoh, M.D., Hidetaka Okada, M.D., Tomoko Tsuzuki, M.D. Akemi Nishigaki, Ph.D., Hideharu Kanzaki, M.D.

Volume 101, Issue 6, Pages 1781–1790.e5



To investigate the role of heart and neural crest derivatives–expressed transcript 2 (HAND2) during decidualization of human endometrial stromal cells (ESCs).


In vitro experiment.


Research laboratory.


Twenty-six patients undergoing hysterectomy for benign reasons.


ESCs were cultured for 12 days with HAND2 small interfering RNA (siRNA) or nonsilencing RNA during decidualization by medroxyprogesterone acetate (MPA) and E2.

Main Outcome Measure(s):

Decidualization was monitored by changes in cellular morphology and the expression of several decidual-specific genes.


HAND2 siRNA effectively suppressed HAND2 levels in ESCs after 12 days of E2 + MPA treatment. ESCs cultured with HAND2 siRNA retained a long fibroblast-like shape, whereas the cells cultured with control siRNA transformed into enlarged polygonal cells. Silencing of HAND2 expression significantly reduced connexin-43 involved in the morphologic changes. HAND2 silencing significantly reduced the mRNA levels of fibulin-1, prolactin, tissue inhibitor of metalloproteinase 3, interleukin-15, and forkhead box O1A (FOXO1A), but had no effect on the mRNA levels of dickkopf-1, serum glucocorticoid kinase 1, and insulin-like growth factor–binding protein 5. HAND2 siRNA effectively suppressed the levels of nuclear FOXO1A protein as a regulator of decidualization.


These results suggest that HAND2 plays a key role in the regulation of progestin-induced decidualization of human ESCs.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

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