Regulation of ovarian granulosa cell by SIRT1 in women with poor ovarian response
10.3969/j.issn.1006-5725.2023.21.004
- VernacularTitle:卵巢低反应女性中沉默信息调节因子1对卵巢颗粒细胞的调控
- Author:
Hui KE
1
;
Lizheng YAN
;
Yu ZHANG
;
Jilong MAO
;
Yufei YAO
Author Information
1. 海南医学院第一附属医院海南省人类生殖与遗传重点实验室,海南医学院第一附属医院生殖医学科,海南医学院第一附属医院海南省地方病(地中海贫血)临床医学研究中心,海南医学院生殖健康与相关疾病研究与转化教育部重点实验室,海南医学院第一附属医院海口市人类遗传资源保藏重点实验室(海口 570102)
- Keywords:
poor ovarian response;
silent information regulator 1;
ovarian granulosa cell;
apoptosis
- From:
The Journal of Practical Medicine
2023;39(21):2709-2717
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the regulation of SIRT1 on ovarian granulosa cell in women with poor ovarian response.Methods A total of 60 women who underwent IVF/ICSI-ET were included in this study,30 women in poor ovarian response(POR)group and 30 women in normal ovarian response(NOR)group.The granulosa cells in follicular fluid were isolated and purified by density gradient centrifugation.The granulosa cells of POR group were treated with SIRT1 agonist resveratrol(RESV)or inhibitor EX527,respectively,and the control group was granulosa cells treated without drugs.mRNA levels of SIRT1 and key enzymes of steroid hormone synthesis(StAR,CYP19,CYP17)in granulosa cells were detected by qPCR.The levels of SIRT1,steroid hormone synthesis key enzymes protein and apoptosis-related protein(Bcl-2,Caspase-3)in granulosa cells were detected by Western blot.The apoptosis rate of granulosa cells was detected by TUNEL method.Determination of estradiol in granulosa cell culture medium by chemiluminescence.Results The mRNA and protein levels of SIRT1 in granulosa cells in POR group were lower than those in NOR group(P = 0.003,P<0.001).RESV up-regulated SIRT1 mRNA and protein levels(P<0.001),up-regulated mRNA and protein levels of steroid hormone synthesis key enzyme(P<0.05).EX527 down-regulated SIRT1 mRNA and protein levels(P = 0.023,0.001),down-regulated mRNA and protein levels of steroid hormone synthesis key enzymes(P<0.05).After RESV treatment,the apoptosis rate of granulosa cells was decreased(P<0.001),the Bcl-2 protein level was increased(P<0.001),and the Caspase-3 protein level was decreased(P<0.001).After EX527 treatment,the apoptosis rate of granulosa cells was increased(P<0.001),the Bcl-2 protein level was decreased(P = 0.003),and the Caspase-3 protein level was increased(P<0.001).Conclusion The SIRT1 level in granulosa cells of POR women was lower than that of NOR women.RESV up-regulated SIRT1 expression in granulosa cells.SIRT1 inhibited granulosa cell apoptosis,increased the level of steroid hormone synthesis key enzyme,and promoted estradiol synthesis in granulosa cell.Therefore,SIRT1 activators such as RESV may be a therapeutic agent to improve ovarian reactivity and increase the number of oocytes obtained in women with POR.
