Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare.
Abstract: Age-related decline in fertility is a consequence of low oocyte number and/or low oocyte competence resulting in pregnancy failure. Transforming growth factor (TGF)-β signalling is a well-studied pathway involved in follicular development and ovulation. Recently, small non-coding RNAs, namely microRNAs (miRNAs), have been demonstrated to regulate several members of this pathway; miRNAs are secreted inside small cell-secreted vesicles called exosomes. The overall goal of the present study was to determine whether altered exosome miRNA content in follicular fluid from old mares is associated with changes in TGF-β signalling in granulosa cells during follicle development. Follicular fluid was collected at deviation (n=6), mid-oestrus (n=6) and preovulation (n=6) for identification of exosomal miRNAs from young (3-12 years) and old (20-26 years) mares. Analysis of selected TGF-β signalling members revealed significantly increased levels of interleukin 6 (IL6) in granulosa cells from mid-oestrus compared with preovulatory follicles, and collagen alpha-2(I) chain (COL1A2) in granulosa cells from deviation compared with preovulatory follicles in young mares. In addition, granulosa cells from old mares had significantly altered levels of DNA-binding protein inhibitor ID-2 (ID2), signal transducer and activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A). Finally, changes in exosomal miRNA predicted to target selected TGF-β members were identified.
Publication Date: 2015-05-07 PubMed ID: 25945781DOI: 10.1071/RD14452Google Scholar: Lookup
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- Journal Article
Summary
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This research article centres on understanding the age-related decline in fertility in mares, notably, its connection with changes observed in the cell-secreted vesicles called exosomes and their microRNAs content, and the Transforming growth factor-β (TGF-β) signalling in granulosa cells during follicle development.
Fertility, Age and TGF-β Signalling
- The study opens by acknowledging a known relationship between the decrease in fertility and age in mares, which is attributed to a reduction in the number of oocytes (the cells which eventually form eggs) and/or the competency of these oocytes, leading to unsuccessful pregnancies.
- Particular focus is cast on TGF-β signalling, a known pathway responsible for follicular development (growth of the sac in the ovary) and ovulation (release of the egg).
Role of Exosomal MicroRNAs
- MicroRNAs (miRNAs) have been established to play a crucial role in the regulation of several elements in the TGF-β pathway. These are small non-coding RNAs found inside exosomes – tiny vesicles secreted by cells.
- The study seeks to establish if changes in the miRNA content in the follicular fluid exosomes from older mares are connected with the alterations in the TGF-β signalling in the granulosa cells (the cells surrounding the developing ovum).
Research Methodology and Findings
- The researchers collected follicular fluid at different stages of development – deviation, mid-oestrus, and preovulation – from both young and old mares.
- Some specific TGF-β signalling members including interleukin 6 (IL6) and collagen alpha-2(I) chain (COL1A2) were found in increased levels in granulosa cells from young mares at certain stages of follicle development.
- Meanwhile, granulosa cells from old mares showed significantly different levels of other members such as DNA-binding protein inhibitor ID-2 (ID2), signal transducer and activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A).
- The authors additionally identified changes in exosomal miRNA which they predict could target the aforementioned TGF-β members.
Conclusion
- This study builds on the understanding of the age-related decline in fertility in mares. It sheds light on the possible role of exosomal miRNA content and its impact on the TGF-β signalling during follicle development. Further research in this arena can contribute beneficially to equine breeding and reproduction strategies.
Cite This Article
APA
da Silveira JC, Winger QA, Bouma GJ, Carnevale EM.
(2015).
Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare.
Reprod Fertil Dev, 27(6), 897-905.
https://doi.org/10.1071/RD14452 Publication
Researcher Affiliations
- Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
- Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
- Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
- Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
MeSH Terms
- Age Factors
- Animals
- Estrous Cycle / metabolism
- Exosome Multienzyme Ribonuclease Complex
- Female
- Follicular Fluid / metabolism
- Granulosa Cells / metabolism
- Horses
- Inhibitor of Differentiation Protein 2 / metabolism
- MicroRNAs / genetics
- MicroRNAs / metabolism
- Oocytes / metabolism
- Ovarian Follicle / metabolism
- STAT1 Transcription Factor / metabolism
- Signal Transduction / physiology
- Transforming Growth Factor beta / metabolism
Citations
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