Female reproductive (ovarian) aging is characterized by a marked decline in quantity and quality of follicles and oocytes, as well as alterations in the surrounding ovarian stroma. In our previous report, we have shown that dietary selenium (Se) insufficiency and supplementation differentially impacted the reproductive efficiency in aging mice; however, the precise understanding of such modulation is still incomplete. In the present study, we sought to determine the impact of low (mildly low level) and moderately high (medium level) Se diets on expression profile of non-selenoprotein genes in the ovaries of aging mice. For this purpose, the aged mice were divided in two groups and fed either a low Se (Se-L; 0.08 mg Se/kg) diet or a moderately high Se (Se-M; 0.33 mg Se/kg) diet. RNA-seq analysis revealed that a total of 168 genes were differentially expressed between the two groups. From these, 72 and 96 differentially expressed genes (DEGs) were found to be upregulated and downregulated, respectively. Gene Ontology (GO) and pathways enrichment (KEGG) analyses revealed that these DEGs were enriched in several key GO terms and biological pathways including PI3K-Akt signaling pathway, steroid hormone biosynthesis, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ovarian steroidogenesis, and Wnt signaling pathway. Further filtering of RNA-seq data revealed that several DEGs such as Star, Hsd3b6, Scd1, Bmp7, Aqp8, Gas1, Fzd1, and Wwc1 were implicated in key ovarian- and fertility-related functions. In addition, some of the DEGs were related to ER homeostasis and/or proteostasis. These results highlight that dietary low and moderately high (medium level) Se diets, in addition to modulation of selenoproteins, can also have an impact on expression of several non-selenoprotein genes in the ovaries of aging mice. To sum up, these findings add more value to our understanding of Se modulation of ovarian functions and female fertility and will pave a way for the focused mechanistic and functional studies in this domain.

女性生殖（卵巢）衰老的特征是卵泡和卵母细胞的数量和质量显着下降，以及周围卵巢基质的改变。在我们以前的报告中，我们已经表明，饮食中硒（Se）的不足和补充对衰老小鼠的生殖效率有不同的影响。但是，对这种调制的精确理解仍然不完整。在本研究中，我们试图确定低（中低水平）和中高（中水平）硒饮食对衰老小鼠卵巢中非硒蛋白基因表达谱的影响。为此，将老年小鼠分为两组，并饲喂低硒（Se-L； 0.08 mg Se / kg）饮食或中度高硒（Se-M； 0.33 mg Se / kg）饮食。RNA-seq分析显示两组之间总共有168个基因差异表达。从这些中，发现分别上调和下调了72和96个差异表达基因（DEG）。基因本体论（GO）和途径富集（KEGG）分析表明，这些DEG富含几个关键的GO术语和生物学途径，包括PI3K-Akt信号传导途径，类固醇激素生物合成，调节干细胞多能性的信号传导途径，Hippo信号传导途径，卵巢类固醇生成和Wnt信号通路。进一步过滤RNA-seq数据显示，一些DEG如 基因本体论（GO）和途径富集（KEGG）分析表明，这些DEG富含几个关键的GO术语和生物学途径，包括PI3K-Akt信号传导途径，类固醇激素生物合成，调节干细胞多能性的信号传导途径，河马信号传导途径，卵巢类固醇生成和Wnt信号通路。进一步过滤RNA-seq数据显示，一些DEG如 基因本体论（GO）和途径富集（KEGG）分析表明，这些DEG富含几个关键的GO术语和生物学途径，包括PI3K-Akt信号传导途径，类固醇激素生物合成，调节干细胞多能性的信号传导途径，Hippo信号传导途径，卵巢类固醇生成和Wnt信号通路。进一步过滤RNA-seq数据显示，一些DEG如Star，Hsd3b6，Scd1，Bmp7，Aqp8，Gas1，Fzd1和Wwc1与卵巢和生育相关的关键功能有关。另外，一些DEG与ER稳态和/或蛋白稳态有关。这些结果表明，低硒和中高硒饮食不仅可以调节硒蛋白，还可以影响衰老小鼠卵巢中几种非硒蛋白基因的表达。综上所述，这些发现为我们对Se对卵巢功能和女性生育能力的调控的理解提供了更多的价值，并将为该领域的重点机制和功能研究铺平道路。