Dataset Information

Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve.

ABSTRACT: PURPOSE:The study aims to determine differences in micro-RNA (miRNA) expression in granulosa (GC) and cumulus cells (CC) between young women with diminished ovarian reserve (DOR) or normal ovarian reserve (NOR). Secondary objective was to identify downstream signaling pathways that could ultimately indicate causes of lower developmental competence of oocytes from young women with DOR. METHODS:The method of the study is prospective cohort study. RESULTS:Of the miRNA, 125 are differentially expressed in GC between DOR and NOR. Only nine miRNA were different in CC; therefore, we focused analysis on GC. In DOR GC, miR-100-5p, miR-16-5p, miR-30a-3p, and miR-193a-3p were significantly downregulated, while miR-155-5p, miR-192-5p, miR-128-3p, miR-486-5p, miR130a-3p, miR-92a-3p, miR-17-3p, miR-221-3p, and miR-175p were increased. This pattern predicted higher cell proliferation in the DOR GC. The primary pathways include MAPK, Wnt, and TGFbeta. CONCLUSIONS:The miRNA pattern identified critical functions in cell proliferation and survival associated with DOR. GC in women with DOR seems to respond differently to the LH surge.

SUBMITTER: Woo I

PROVIDER: S-EPMC6150892 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve.

Woo Irene I Christenson Lane K LK Gunewardena Sumedha S Ingles Sue Ann SA Thomas Semara S Ahmady Ali A Chung Karine K Bendikson Kristin K Paulson Richard R McGinnis Lynda K LK

Journal of assisted reproduction and genetics 20180709 10

<h4>Purpose</h4>The study aims to determine differences in micro-RNA (miRNA) expression in granulosa (GC) and cumulus cells (CC) between young women with diminished ovarian reserve (DOR) or normal ovarian reserve (NOR). Secondary objective was to identify downstream signaling pathways that could ultimately indicate causes of lower developmental competence of oocytes from young women with DOR.<h4>Methods</h4>The method of the study is prospective cohort study.<h4>Results</h4>Of the miRNA, 125 are ...[more]

PMID: 29987422

Similar Datasets

Project description:BackgroundInfertility is a global reproductive-health problem, and diminished ovarian reserve (DOR) is one of the common causes of female infertility. Long noncoding RNAs (lncRNAs) are crucial regulators of numerous physiological and pathological processes in humans. However, whether lncRNAs are involved in the development of DOR remains to be elucidated.MethodsOvarian granulosa cells (OGCs) extracted from infertile women with DOR and from women with normal ovarian reserve (NOR) were subjected to high-throughput sequencing. Comprehensive bioinformatics analysis was conducted to identify the differential expression of messenger RNAs (mRNAs) and lncRNAs. Sequencing results were validated by the selection of lncRNAs and mRNAs using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsCompared with the NOR group, a total of 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 mRNAs had differential expression between the two groups. Of these, 169 were upregulated and 288 were downregulated. Bioinformatics analysis revealed that the differentially expressed genes of mRNA and lncRNAs were considerably enriched in "cell adhesion and apoptosis", "steroid biosynthesis", and "immune system". A co-expression network comprising lncRNAs and their predicted target genes revealed the possible involvement of the "thyroid hormone signaling pathway" and "protein binding, digestion and absorption" in DOR pathogenesis. The expression of SLC16A10 was positively regulated by multiple lncRNAs. After RT-qPCR validation of seven differentially expressed lncRNAs and mRNAs, respectively, the expression of lncRNA NEAT1, GNG12, ZEB2-AS1, and mRNA FN1, HAS3, RGS4, SUOX were in accordance with RNA-sequencing.ConclusionsWe presented the first data showing that the expression profiles of lncRNA and mRNA in OGCs between NOR and DOR patients using RNA sequencing. The lncRNAs and mRNAs that we identified may serve as novel diagnostic biomarkers for patients with DOR.

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.

Project description:Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and 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 during an IVF cycle (n = 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n = 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT-PCR (qRT-PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT-PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value = 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value = 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.

Dataset Information

Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve.

Publications

Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets