Abstract
There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function.
Highlights
Ovarian aging results in the cessation of ovarian function, that is, anovulation and a decrease in gonadal steroids secretion
To characterize the genes that are associated with mouse ovarian aging, we examined the gene expression profile of secondary follicles from young and old mouse ovaries
After normalization of raw data for all three biological replicates, the R package significance analysis of microarray (SAM) was used to identify genes that are differentially expressed in secondary follicles from young and old mouse ovaries
Summary
Ovarian aging results in the cessation of ovarian function, that is, anovulation and a decrease in gonadal steroids secretion. The reproductive aging process is considered to be dominated by the gradual decrease of both the quantity and the quality of the oocytes residing within the follicles present in the ovarian cortex [4]. Females have approximately 1-2 million primordial follicles at birth [5, 6]. The number of follicles decreases gradually with increasing age through atresia with some 300,000 to 400,000 primordial follicles remaining at menarche [4, 7]. The number of primordial follicles declines until a critical threshold when only about 1000 left at the time of menopause [8,9,10]
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