Regulation of replanted progesterone on stress signal in endoplasmic reticulum stress during menstruation in mice at different periods / 医学研究生学报

ABSTRACT

Objective　Endoplasmic reticulum stress may be involved in the menstrual process, but the detailed mechanism is unclear. This article is to explore the effect of progesterone replantation at different periods on the endoplasmic reticulum stress-induced autophagy and apoptosis in mice during menstruation.　Methods　Mice were divided into 12h replantation group, 16h replantation group and the withdrawal group according to random number table, with 10 mice in each group. 12h (12h replantation group) and 16h (16h replantation group) after the withdrawal of progesterone, replanted respectively with progesterone tube, and withdrawal group were not replanted. Mice in each group were sacrificed 24h after the withdrawal of progesterone and were collected bilateral uterine horns. The expression and localization of t-PERK, p-PERK, t-eIF2α, p-eIF2α, ATF4, CHOP and Caspase12 mRNA and proteins in mouse endometrial tissues were detected by qPCR, Western blot and immunohistochemistry.　Results　At the mRNA level, the PERK and eIF2α(1.000 ± 0.000) of the 12h replantation group were significantly higher than those of the 16h replantation group (0.450 ± 0.049, 0.330 ± 0.015) and the withdrawal group (0.260 ± 0.233, 0.195 ± 0.014). The difference was statistically significant (P<0.05), and the 16h replantation group was higher than the withdrawal group (P<0.05). At the protein level, p-PERK / t-PERK (0.606 ± 0.051) and p-eIF2α / t-eIF2α (0.795 ± 0.074) in 12h replantation group were significantly higher than those in 16h replantation group (0.367 ± 0.019, 0.503 ± 0.038) and withdrawal group (0.243 ± 0.020, 0.293 ± 0.020). The difference was statistically significant (P<0.05) and the 16h replantation group was significantly higher than the withdrawal group. At the mRNA and protein levels, ATF4 of 12h replantation group were higher than 16h replantation group and the withdrawal group (P <0.05) , and the 16h replantation group was higher than the withdrawal group. The proteins of p-PERK, p-eIF2α and ATF4 are mainly expressed in the cytoplasm of decidual stromal cells which located at the junction of basal layer and decidualized stromal cells. At mRNA and protein levels, the expression levels of CHOP and Caspase12 in 12h replantation group were significantly lower than those in 16h replantation group , were also lower than the withdrawal group, and the 16h replantation group was lower than the withdrawal group (P<0.05). The proteins of CHOP and Caspase12 are mainly localized in cytoplasm of adequately decidualized stromal cells and the glandular epithelium cells.　Conclusion　Replantation of progesterone before the critical period of menstruation (12h) can effectively block the onset of menstruation in mice, which may be achieved by maintaining the expression of PERK/eIF2α/ATF4 signal and blocking the expression of apoptotic signaling pathway members CHOP and Caspase 12 in endometrial stromal cells. And this effect can only be partially achieved by progesterone replantationing after the critical period of menstruation (16h).