Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress

Capsule:
Androgens inhibit cell death of decidualizing endometrial stromal cells exposed to oxidative stress signals. Therefore, androgens might play a critical role for decidua processes of embryo implantation and trophoblast invasion.

Authors:
Takeshi Kajihara, M.D., Ph.D., Hideno Tochigi, M.D., Japarath Prechapanich, M.D., Satomi Uchino, Atsuo Itakura, M.D., Ph.D., Jan J. Brosens, M.D., Ph.D., Osamu Ishihara, M.D., Ph.D.
Volume 97, Issue 1 , Pages 185-191, January 2012

Objective:
To investigate the effect of androgens on the expression of genes involved in oxidative stress resistance in decidualized human endometrial stromal cells (HESCs).

Design:
In vitro experiment.

Setting:
University hospital.

Patient(s):
Premenopausal women undergoing hysterectomy for uterine fibroids.

Intervention(s):
Human endometrial stromal cells isolated from hysterectomy specimens were decidualized with 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and P in the presence or absence of dihydrotestosterone (DHT) at various concentrations. Hydrogen peroxide was used as a source of reactive oxygen species.

Main Outcome Measure(s):
Prolactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression.

Result(s):
Prolactin production was induced in HESCs in response to 8-br-cAMP and P. Dihydrotestosterone further enhanced the secretion of PRL in cells treated with 8-br-cAMP plus P. The effect of DHT was blocked by the antiandrogen flutamide. Dihydrotestosterone enhanced resistance to oxidative stress–induced apoptosis on decidualized HESCs. Moreover, DHT enhanced FOXO1 expression in parallel with increased SOD2 protein but not with SOD1.

Conclusion(s):
Androgens might play a critical role in the decidualization process at the time of embryo implantation and trophoblast invasion by promoting resistance to oxidative stress.

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