Hexestrol Deteriorates Oocyte Quality via Perturbation of Mitochondrial Dynamics and Function.

Hexestrol Deteriorates Oocyte Quality via Perturbation of Mitochondrial Dynamics and Function.
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DOI:
10.3389/fcell.2021.708980
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发表时间:
2021
影响因子:
5.5
通讯作者:
Duan X
Duan X
中科院分区:
生物学2区
文献类型:
--
作者:
Niu D;Chen KL;Wang Y;Li XQ;Liu L;Ma X;Duan X

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己雌酚(HES)是一种合成的非甾体雌激素,被广泛非法用于提高畜牧业和水产养殖业的增长率。羟乙基淀粉也可以从治疗的动物和环境中转移到人类身上。已证实羟乙基淀粉对卵巢功能和卵子发生有不良影响,但其潜在机制尚未明确。为了了解HES如何影响女性卵巢功能的潜在机制,我们通过检查卵母细胞成熟过程中的关键事件来评估卵母细胞的质量。我们发现,羟乙基淀粉对卵母细胞质量有不利影响,表现为卵母细胞成熟能力和早期胚胎发育能力下降。具体而言,HES暴露的卵母细胞表现出异常的微管成核和纺锤体组装,导致减数分裂停滞。此外,羟乙基淀粉暴露破坏了线粒体分布和线粒体分裂与融合的平衡,导致线粒体膜电位异常和活性氧的积累。最后,我们发现,羟乙基淀粉暴露可以增加细胞内钙离子水平,并诱导DNA损伤和早期凋亡。总之,这些结果表明,线粒体功能障碍和正常线粒体分裂和融合动力学的扰动可能是羟乙基淀粉暴露后卵母细胞质量降低的主要原因。
Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be transferred to humans from treated animals and the environment. HES has been shown to have an adverse effect on ovarian function and oogenesis, but the potential mechanism has not been clearly defined. To understand the potential mechanisms regarding how HES affect female ovarian function, we assessed oocyte quality by examining the critical events during oocyte maturation. We found that HES has an adverse effect on oocyte quality, indicated by the decreased capacity of oocyte maturation and early embryo development competency. Specifically, HES-exposed oocytes exhibited aberrant microtubule nucleation and spindle assembly, resulting in meiotic arrest. In addition, HES exposure disrupted mitochondrial distribution and the balance of mitochondrial fission and fusion, leading to aberrant mitochondrial membrane potential and accumulation of reactive oxygen species. Lastly, we found that HES exposure can increase cytosolic Ca2+ levels and induce DNA damage and early apoptosis. In summary, these results demonstrate that mitochondrial dysfunction and perturbation of normal mitochondrial fission and fusion dynamics could be major causes of reduced oocyte quality after HES exposure.
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