Identifying Molecular Determinants of Infertility in Men (MODIFY)
Study Details
Study Description
Brief Summary
The purpose of this study is to understand the underlying mechanisms of infertility caused by unknown factors. The investigator propose to identify small non-coding RNA (sncRNA) biomarkers of infertility and advance towards developing a more accurate and robust approach for infertility diagnosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The goal of the study is to identify small non-coding RNA signatures of infertility in men through the comparison of sperm sncRNA profiles from around 100 men (21-50 years of age). The participants will be classified into fertile and infertile groups by the conventional method.
Through the project, the investigator intends to understand the underlying mechanisms of idiopathic infertility. By utilizing semen as liquid biopsy, through sperm sncRNA profiling and comparison (infertile vs fertile). The investigator proposes to identify the sncRNA (miRNAs, piRNAs and tRFs) as biomarkers of infertility.
The investigator proposes to generate a validated signature of sncRNAs that will help in selecting high quality sperms for IVF.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Healthy fertile male No intervention for this study. |
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| Healthy infertile male No intervention for this study. |
Outcome Measures
Primary Outcome Measures
- Semen/Sperm quantity analysis [1 week]
sperm count and concentration
- Semen/Sperm quality analysis [1 week]
semen pH, semen volume, sperm motility, sperm morphology, sperm vitality
- Fertility classification [1 week]
Classification into fertile/infertile groups based on the fertility measures.
- Sperm RNA extraction and sequencing [3 months]
Sperm RNA extraction and sequencing
Secondary Outcome Measures
- Expression profiling of sncRNA [3-6 months]
Counts of miRNA, piRNA, tRF from the sequenced data through Bioinformatics analysis. All three sncRNA will be quantified from the RNA sequencing data using bioinformatics tools, with the same unit of measure.
- Comparison of the expression profiles [3-6 months]
Comparison of the expression profiles between the two groups (infertile vs fertile)
Eligibility Criteria
Criteria
Inclusion Criteria
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Male, aged 21 - 50 years old
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Proficient in English language
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Willing to comply to study protocol
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Able to provide written informed consent
Exclusion Criteria
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Current and/or previous diagnosis of Tuberculosis, Acquired immunodeficiency syndrome (AIDs), and other sexually transmitted diseases
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Experiencing severely limited mobility (eg. Wheelchair bound, need walking aid)
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Diagnosed with severe unstable mental conditions (eg. Dementia, or cognitive impairment)
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Alcohol or drug abuse
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Human Development Research Centre (HDRC) | Singapore | Singapore | 117597 |
Sponsors and Collaborators
- Singapore Institute for Clinical Sciences
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
- Abu-Halima M, Hammadeh M, Backes C, Fischer U, Leidinger P, Lubbad AM, Keller A, Meese E. Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertil Steril. 2014 Oct;102(4):989-997.e1. doi: 10.1016/j.fertnstert.2014.07.001. Epub 2014 Aug 6.
- Alves MBR, Celeghini ECC, Belleannee C. From Sperm Motility to Sperm-Borne microRNA Signatures: New Approaches to Predict Male Fertility Potential. Front Cell Dev Biol. 2020 Aug 21;8:791. doi: 10.3389/fcell.2020.00791. eCollection 2020.
- Cao XW, Lin K, Li CY, Yuan CW. [A review of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th edition)]. Zhonghua Nan Ke Xue. 2011 Dec;17(12):1059-63. Chinese.
- Cui L, Fang L, Shi B, Qiu S, Ye Y. Spermatozoa micro ribonucleic acid-34c level is correlated with intracytoplasmic sperm injection outcomes. Fertil Steril. 2015 Aug;104(2):312-7.e1. doi: 10.1016/j.fertnstert.2015.05.003. Epub 2015 Jun 6.
- Donkin I, Barres R. Sperm epigenetics and influence of environmental factors. Mol Metab. 2018 Aug;14:1-11. doi: 10.1016/j.molmet.2018.02.006. Epub 2018 Feb 27.
- Hua M, Liu W, Chen Y, Zhang F, Xu B, Liu S, Chen G, Shi H, Wu L. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discov. 2019 Apr 9;5:20. doi: 10.1038/s41421-019-0087-9. eCollection 2019. No abstract available.
- Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018 Apr 26;4(2):dvy007. doi: 10.1093/eep/dvy007. eCollection 2018 Apr.
- Vashisht A, Gahlay GK. Using miRNAs as diagnostic biomarkers for male infertility: opportunities and challenges. Mol Hum Reprod. 2020 Apr 24;26(4):199-214. doi: 10.1093/molehr/gaaa016.
- Zhang Y, Shi J, Rassoulzadegan M, Tuorto F, Chen Q. Sperm RNA code programmes the metabolic health of offspring. Nat Rev Endocrinol. 2019 Aug;15(8):489-498. doi: 10.1038/s41574-019-0226-2. Epub 2019 Jun 24.
- 2023-085