Phospholipid Phosphatase 3 (PLPP3) Induces Oxidative Stress to Accelerate Ovarian Aging in Pigs
文献类型： 外文期刊
作者： Quan, Hongyan 1 ; Guo, Yixuan 1 ; Li, Shuo 1 ; Jiang, Yao 2 ; Shen, Qingpeng 1 ; He, Yingting 1 ; Zhou, Xiaofeng 1 ; Yuan, Xiaolong 1 ; Li, Jiaqi 1 ;
作者机构： 1.South China Agr Univ, Coll Anim Sci, Natl Engn Res Ctr Breeding Swine Ind, Guangdong Prov Key Lab Agroanim Genom & Mol Breedi, Guangzhou 510642, Peoples R China
2.Murdoch Univ, Sch Med Mol & Forens Sci, Murdoch, WA 6150, Australia
3.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Guangdong Lab Lingnan Modern Agr,Genome Anal Lab M, Shenzhen 518120, Peoples R China
4.Murdoch Univ, Hlth Futures Inst, Ctr Hlth Ageing, Murdoch, WA 6150, Australia
关键词： ovarian aging; PLPP3; oxidative stress; ferroptosis; autophagy; pigs
期刊名称：CELLS （ 影响因子：5.2； 五年影响因子：6.1 ）
ISSN：
年卷期： 2024 年 13 卷 17 期
页码：
收录情况： SCI
摘要： Ovarian aging results in reproductive disorders and infertility in mammals. Previous studies have reported that the ferroptosis and autophagy caused by oxidative stress may lead to ovarian aging, but the mechanisms remain unclear. In this study, we compared the morphological characteristics between the aged and young ovaries of pigs and found that the aged ovaries were larger in size and showed more corpora lutea. TUNEL assay further showed that the apoptosis level of granulosa cells (GCs) was relatively higher in the aged ovaries than those in young ovaries, as well as the expressions of autophagy-associated genes, e.g., p62, ATG7, ATG5, and BECN1, but that the expressions of oxidative stress and aging-associated genes, e.g., SOD1, SIRT1, and SIRT6, were significantly lower. Furthermore, the RNA-seq, Western blotting, and immunofluorescence suggested that phospholipid phosphatase 3 (PLPP3) protein was significantly upregulated in the aged ovaries. PLPP3 was likely to decrease the expressions of SIRT1 and SIRT6 to accelerate cellular senescence of porcine GCs, inhibit the expressions of SOD1, CAT, FSP1, FTH1, and SLC7A11 to exacerbate oxidative stress and ferroptosis, and arouse autophagy to retard the follicular development. In addition, two SNPs of PLPP3 promoter were significantly associated with the age at puberty. g.155798586 (T/T) and g.155798718 (C/C) notably facilitated the mRNA and protein level of PLPP3. In conclusion, PLPP3 might aggravate the oxidative stress of GCs to accelerate ovarian aging, and two molecular markers of PLPP3 were identified for ovarian aging in pigs. This work not only contributes to investigations on mechanisms for ovarian aging but also provides valuable molecular markers to postpone ovarian aging in populations.
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