Hisayuu Shindoh1, Hidetaka Okada2, Tomoko Tsuzuki1, Akemi Nishigaki1, Hideharu Kanzaki1. 1. Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. 2. Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. Electronic address: hokada@hirakata.kmu.ac.jp.
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.
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.
Authors: Erik C Mazur; Yasmin M Vasquez; Xilong Li; Ramakrishna Kommagani; Lichun Jiang; Rui Chen; Rainer B Lanz; Ertug Kovanci; William E Gibbons; Francesco J DeMayo Journal: Endocrinology Date: 2015-03-17 Impact factor: 4.736
Authors: Ramakrishna Kommagani; Maria M Szwarc; Yasmin M Vasquez; Mary C Peavey; Erik C Mazur; William E Gibbons; Rainer B Lanz; Francesco J DeMayo; John P Lydon Journal: PLoS Genet Date: 2016-04-01 Impact factor: 5.917