Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of human granulosa cells from individuals with diminished ovarian reserve and egg donors

ABSTRACT: Diminished ovarian reserve (DOR) is a challenging diagonosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. In this study, our aim was to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from approximately age-matched egg donors to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development dring an IVF cycle (n=13). Egg donors with normal ovarian reserve comprised the control group (n=13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic difference between the groups. Confirmatory studies were undertaken with qRT-PCR. Multiple significant differences in gene expression were observed between the DOR patients and egg donors.

ORGANISM(S): Homo sapiens

DISEASE(S): Diminished Ovarian Reserve (DOR)

SUBMITTER: Racowsky Catherine

PROVIDER: E-MTAB-391 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Infertility is one of the major health problems and the third most common disease, and diminished ovarian reserve (DOR) is a common cause of infertility. DOR is defined as decreased number or quality of oocytes in reproductive-age women, but the underlying molecular mechanisms remain unclear. Long noncoding RNAs (lncRNAs) has been recognized to play an important role in physiological and pathological processes of the human body, but it is unknown whether lncRNAs are involved in the development of DOR. Methods: The ovarian granulosa cells from infertility women with DOR and normal ovarian reserve (NOR) were obtained and subjected to high-throughput sequencing. A comprehensive bioinformatics analysis was conducted to characterize the mRNAs and lncRNAs expression profiles between DOR and NOR women. Then, the sequencing results were validated by selected randomly lncRNAs using real-time quantitative PCR. Results: A total of 92,853 lncRNAs transcripts were identified between DOR and NOR GCs. Compared with NOR control, 244 lncRNAs were upregulated (53 known and 191 novel) and 222 lncRNAs were downregulated (36 known and 186 novel) in the DOR group. Similarly, 457 differently expressed mRNAs were found between the two groups, with 169 and 288 up- and downregulated respectively. Further functional analysis revealed that differentially expressed genes of mRNA and lncRNA were significantly enriched in various biological processes such as cell adhesion and apoptosis, steroid biosynthesis, and immune system. The results of correlated expression networks between lncRNAs and their predicted target genes uncovered the possible involvement of the thyroid hormone signaling pathway and protein binding, digestion and absorption in the pathogenesis of DOR and showed that SLC16A10 is positively regulated by multiple lncRNAs. In addition, it was verified that the expression patterns of three of the seven selected differentially expressed lncRNAs were consistent with RNA-Seq. Aberrant lncRNAs might be used to develop new diagnostic biomarkers or drugs to target DOR. Conclusion: This study is the first to elucidate the lncRNA and mRNA expression profiles between NOR and DOR patients in the ovarian granulosa cells using sequencing technology. The lncRNAs identified in this study can potentially be novel diagnostic biomarkers and therapeutic targets for DOR.

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Transcription profiling by array of human granulosa cells from individuals with diminished ovarian reserve and egg donors

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