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

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

Authors:
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

Abstract:

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

Design:
In vitro experiment.

Setting:
Research laboratory.

Patient(s):
Twenty-six patients undergoing hysterectomy for benign reasons.

Intervention(s):
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.

Result(s):
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.

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

Translate »