Institute of Animal Physiology, Centre of Biosciences of the Slovak Academy of Sciences, Šoltésovej, Košice, Slovakia.
Biol Reprod. 2019 Feb 1;100(2):351-364. doi: 10.1093/biolre/ioy196.
To investigate possible involvement of glucocorticoid receptor (GR) in mediating effects of maternal stress or therapeutically administered glucocorticoids on early embryo, we analyzed the expression of GR subtypes in ovulated mouse oocytes and preimplantation embryos. RT-PCR analysis results showed that GRα and GRγ transcripts are relatively highly expressed in mouse oocytes, and both transcripts are present at lower amounts in preimplantation embryos. We also detected low expression of two other splice variants, GRβ and a transcript orthologous to the human GR-P subtype, mainly at the blastocyst stage. Using western blot analysis, we detected several GR protein bands that differed in size between oocytes and preimplantation embryos. To compare the effects of corticosterone (a major endogenous glucocorticoid in rodents) and dexamethasone (a synthetic glucocorticoid) on early embryos, we cultured mouse preimplantation embryos in the presence of these glucocorticoids. Corticosterone showed a strong inhibitory effect on embryo development (starting from a 50 μM concentration), without a significant influence on apoptosis incidence. On the other hand, dexamethasone induced apoptosis in early embryo cells (starting from a 1.5 μM concentration), and its effect on embryo development was less detrimental than that found with the same dose of corticosterone. In summary, our results showed that different GR subtypes are expressed in ovulated mouse oocytes and preimplantation embryos and that the composition of GR subtypes changes during early embryo development. Moreover, we found significant differences in the effects of the two glucocorticoids on early embryo development, which might be associated with activation of different GR subtypes.
为了研究糖皮质激素受体 (GR) 是否参与介导母体应激或治疗性给予的糖皮质激素对早期胚胎的影响，我们分析了 GR 亚型在排卵小鼠卵母细胞和着床前胚胎中的表达。RT-PCR 分析结果表明，GRα 和 GRγ 转录本在小鼠卵母细胞中相对高度表达，而在着床前胚胎中则以较低的量存在。我们还检测到两种其他剪接变体，GRβ 和与人 GR-P 亚型同源的转录本，主要在囊胚阶段低表达。使用 Western blot 分析，我们在卵母细胞和着床前胚胎之间检测到大小不同的几种 GR 蛋白带。为了比较皮质酮（啮齿动物中主要的内源性糖皮质激素）和地塞米松（一种合成的糖皮质激素）对早期胚胎的影响，我们在这些糖皮质激素存在的情况下培养小鼠着床前胚胎。皮质酮对胚胎发育表现出强烈的抑制作用（从 50 μM 浓度开始），对细胞凋亡发生率没有显著影响。另一方面，地塞米松诱导早期胚胎细胞凋亡（从 1.5 μM 浓度开始），其对胚胎发育的影响比相同剂量的皮质酮小。总之，我们的结果表明，不同的 GR 亚型在排卵的小鼠卵母细胞和着床前胚胎中表达，并且 GR 亚型的组成在早期胚胎发育过程中发生变化。此外，我们发现两种糖皮质激素对早期胚胎发育的影响存在显著差异，这可能与不同 GR 亚型的激活有关。
