Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia.
Cells. 2024 Aug 25;13(17):1421. doi: 10.3390/cells13171421.
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., , , , and , but that the expressions of oxidative stress and aging-associated genes, e.g., , , and , 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. was likely to decrease the expressions of and to accelerate cellular senescence of porcine GCs, inhibit the expressions of , , , , and to exacerbate oxidative stress and ferroptosis, and arouse autophagy to retard the follicular development. In addition, two SNPs of 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 In conclusion, might aggravate the oxidative stress of GCs to accelerate ovarian aging, and two molecular markers of 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.
卵巢衰老导致哺乳动物生殖障碍和不孕。先前的研究报道，氧化应激引起的铁死亡和自噬可能导致卵巢衰老，但机制尚不清楚。在这项研究中，我们比较了猪的衰老和年轻卵巢的形态特征，发现衰老的卵巢体积较大，黄体较多。TUNEL 检测进一步表明，衰老卵巢中颗粒细胞（GCs）的凋亡水平相对较高，衰老相关基因如、、、和的表达也较低。此外，RNA-seq、Western blot 和免疫荧光结果表明，磷脂磷酸酶 3（PLPP3）蛋白在衰老卵巢中显著上调。可能通过降低和的表达加速猪 GCs 的细胞衰老，抑制、、、和的表达加剧氧化应激和铁死亡，并引起自噬以延缓卵泡发育。此外，的启动子的两个 SNP g.155798586（T/T）和 g.155798718（C/C）显著影响的 mRNA 和蛋白水平。总之，可能通过加剧 GCs 的氧化应激来加速卵巢衰老，并且鉴定了两个的分子标记物用于猪的卵巢衰老。这项工作不仅有助于研究卵巢衰老的机制，还为延缓人群卵巢衰老提供了有价值的分子标记物。
