Ran Feng, Chen Si-Ting, Li Meng-Yuan, Jin Dan-Dan, Yang Zeng-Ming
College of Animal Science, Guizhou University, Guiyang 550025, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Int J Mol Sci. 2025 Apr 26;26(9):4122. doi: 10.3390/ijms26094122.
Diethylstilbestrol (DES) is a synthetic non-steroidal estrogen, which was widely used to prevent preterm birth and abortion from the 1940s to the 1970s. DES can increase the incidence of infertility, the abnormal reproductive tract, and autoimmune diseases. However, the mechanism underlying DES on early pregnancy in mice is unclear. This study evaluated the effects of DES on early pregnancy in mice, especially on uterine receptivity and decidualization. Newborn female mice were subcutaneously injected with 0.1 mg/kg DES, 1 mg/kg DES, or sesame oil as controls for 5 consecutive days. At 6 weeks old, these female mice were mated with 8-12-week-old fertile males to obtain pregnancy. The uteri of these mice were collected on days 4, 5, and 8 of pregnancy for further analysis. On days 5 and 8 of pregnancy, the number of implantation sites in 0.1 mg/kg DES group is similar to the control group, while almost no implantation sites are detected in the 1 mg/kg DES group. On day 4 of pregnancy, there was no significant difference in uterine receptive molecules between the control group and the 0.1 mg/kg DES group. However, the levels of uterine receptive molecules in the 1 mg/kg DES group are abnormal. In addition, 6 μM DES significantly inhibits mouse in vitro decidualization. The excessive activation of pyroptosis may lead to pregnancy failure. The pyroptosis-related molecules in the 1 mg/kg DES group were significantly up-regulated, suggesting that DES may contribute to pregnancy failure by over-activating pyroptosis.
己烯雌酚（DES）是一种合成的非甾体雌激素，在20世纪40年代至70年代被广泛用于预防早产和流产。DES会增加不孕、生殖道异常和自身免疫性疾病的发生率。然而，DES对小鼠早期妊娠的潜在机制尚不清楚。本研究评估了DES对小鼠早期妊娠的影响，特别是对子宫接受性和蜕膜化的影响。新生雌性小鼠连续5天皮下注射0.1mg/kg DES、1mg/kg DES或作为对照的芝麻油。6周龄时，将这些雌性小鼠与8至12周龄的可育雄性小鼠交配以实现妊娠。在妊娠第4、5和8天收集这些小鼠的子宫进行进一步分析。在妊娠第5天和第8天，0.1mg/kg DES组的着床点数与对照组相似，而1mg/kg DES组几乎未检测到着床点。在妊娠第4天，对照组和0.1mg/kg DES组之间的子宫接受分子无显著差异。然而，1mg/kg DES组的子宫接受分子水平异常。此外，6μM DES显著抑制小鼠体外蜕膜化。细胞焦亡的过度激活可能导致妊娠失败。1mg/kg DES组中与细胞焦亡相关的分子显著上调，表明DES可能通过过度激活细胞焦亡导致妊娠失败。
