Yuan Hong-Jie, Han Xiao, He Nan, Wang Guo-Liang, Gong Shuai, Lin Juan, Gao Min, Tan Jing-He
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P. R. China.
Sci Rep. 2016 Apr 4;6:24036. doi: 10.1038/srep24036.
Previous studies indicate that stress damages oocytes with increased secretion of glucorticoids. However, although injection of female mice with cortisol decreased oocyte competence, exposure of mouse oocytes directly to physiological or stress-induced concentrations of glucorticoids did not affect oocyte maturation and embryo development. This study has explored the mechanisms by which glucocorticoids impair oocyte competence. Female mice were injected with cortisol and the effects of cortisol-injection on oocyte competence, ovarian cell apoptosis and Fas/FasL activation were observed. The results showed that cortisol-injection decreased (a) oocyte developmental potential, (b) the E2/P4 ratio in serum and ovaries, and (c) expression of insulin-like growth factor 1, brain-derived neurotrophic factor and glucocorticoid receptor in mural granulosa cells (MGCs), while increasing levels of (a) cortisol in serum and ovaries, (b) apoptosis in MGCs and cumulus cells (CCs), (c) FasL secretion in ovaries and during oocyte maturation in vitro, and (d) Fas in MGCs, CCs and oocytes. The detrimental effects of cortisol-injection on oocyte competence and apoptosis of MGCs and CCs were significantly relieved when the gld (generalized lymphoproliferative disorder) mice harboring FasL mutations were observed. Together, the results suggested that glucocorticoids impair oocyte competence by triggering apoptosis of ovarian cells via activating the Fas system.
先前的研究表明，应激会因糖皮质激素分泌增加而损害卵母细胞。然而，尽管给雌性小鼠注射皮质醇会降低卵母细胞的能力，但将小鼠卵母细胞直接暴露于生理浓度或应激诱导浓度的糖皮质激素下，并不会影响卵母细胞的成熟和胚胎发育。本研究探讨了糖皮质激素损害卵母细胞能力的机制。给雌性小鼠注射皮质醇，并观察注射皮质醇对卵母细胞能力、卵巢细胞凋亡和Fas/FasL激活的影响。结果显示，注射皮质醇会降低：(a)卵母细胞的发育潜力；(b)血清和卵巢中的E2/P4比值；(c)壁颗粒细胞（MGCs）中胰岛素样生长因子1、脑源性神经营养因子和糖皮质激素受体的表达，同时增加：(a)血清和卵巢中的皮质醇水平；(b)MGCs和卵丘细胞（CCs）中的细胞凋亡；(c)卵巢中以及体外卵母细胞成熟过程中的FasL分泌；(d)MGCs、CCs和卵母细胞中的Fas。当观察携带FasL突变的gld（全身性淋巴增殖性疾病）小鼠时，注射皮质醇对卵母细胞能力以及MGCs和CCs凋亡的有害影响得到了显著缓解。总之，结果表明糖皮质激素通过激活Fas系统触发卵巢细胞凋亡，从而损害卵母细胞能力。
