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山奈酚改善了小鼠体内外排卵后卵母细胞老化。

Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

机构信息

Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen Fujian 361102, China; College of Life Sciences, Southwest Forestry University, Kunming Yunnan 650000, China; Reproductive Medical Center, Zhanjiang Jiuhe Hospital, Zhanjiang Guangdong 524094, China.

Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen Fujian 361102, China.

出版信息

Reprod Biomed Online. 2022 Dec;45(6):1065-1083. doi: 10.1016/j.rbmo.2022.07.005. Epub 2022 Jul 19.

Abstract

RESEARCH QUESTION

Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity?

DESIGN

The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo.

RESULTS

Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%).

CONCLUSIONS

Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

摘要

研究问题

山奈酚是否能减轻排卵后卵母细胞老化,从而维持其早期胚胎发育能力?

设计

通过短期山奈酚给药(将成熟卵母细胞在含有山奈酚的培养基中培养 12 小时;将适量的山奈酚通过灌胃给予小鼠 21 天),在体内和体外研究山奈酚对排卵后老化的影响。通过免疫荧光评估纺锤体形态和染色体排列、氧化应激水平和间隙连接。通过 IVF 检测每个卵母细胞组的受精能力和早期胚胎发育能力。使用老化卵母细胞模型受精,以探讨山奈酚是否可以改善不良妊娠结局。通过 RNA 测序和定量聚合酶链反应鉴定体内山奈酚缓解排卵后卵母细胞老化的细胞途径。

结果

山奈酚处理改变了老化卵母细胞中的各种过程,包括氧化应激、过氧化物酶体、TNF 信号、cAMP 信号和间隙连接途径。调节了几个重要基因的表达,如 Sirt1、Mapk1、Ampk 和 Foxo3。此外,山奈酚改善了受精老化卵母细胞的不良妊娠结局。IVF 结果表明,山奈酚可以部分抵消卵母细胞老化对受精能力(原核:山奈酚 69.08±2.37%对老化 38.95±3.58%)和早期胚胎发育(囊胚:山奈酚 50.02±3.34%对老化 30.83±5.46%)的影响。

结论

我们的结果表明,山奈酚可能是一种有效的天然抗氧化剂,对畜牧业有意义,并可能有助于提高 IVF 和 ICSI 的成功率。需要进一步的临床试验。

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