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Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation
Mina Moayeri1, Shiva Irani1, Marefat Ghaffari Novin2
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Reproductive Sciences (Thousand Oaks, Calif.)
|July 16, 2024
Summary
Infertile men with high sperm DNA fragmentation show reduced expression of DNA repair genes and DDSR1, a long non-coding RNA. These factors may contribute to male infertility and serve as potential diagnostic markers.
Area of Science:
- Reproductive biology
- Molecular genetics
- Genomics
Background:
- Sperm DNA fragmentation (SDF) is a key factor in male infertility, but its molecular mechanisms remain unclear.
- Long non-coding RNAs (LncRNAs), particularly DNA damage-sensitive RNA1 (DDSR1), are emerging as significant players in male reproductive health.
- Understanding genes involved in DNA damage response is crucial for addressing male infertility.
Purpose of the Study:
- To investigate the role of LncRNA DDSR1 and DNA damage response genes in male infertility associated with high sperm DNA fragmentation.
- To identify potential molecular markers for diagnosing male infertility related to DNA damage.
Main Methods:
- Construction of a protein-protein interaction network (PPIN) using the STRING database.
- Functional classification of genes using webgestalt servers.
- Real-time PCR analysis to compare gene expression in infertile males (SDF ≥ 25%) and healthy controls (SDF < 25%).
Main Results:
- Infertile men with abnormal sperm DNA fragmentation index (DFI) exhibited significantly lower expression of DDSR1, BRCA1, MRE11A, RAD51, and NBN compared to controls.
- Pathway analysis revealed the involvement of these genes in critical processes including DNA repair, cell cycle, meiosis, and reproduction.
Conclusions:
- Downregulation of LncRNA DDSR1 and DNA damage response genes is associated with abnormal sperm DNA fragmentation in infertile males.
- These molecular factors may contribute to the pathogenesis of sperm DNA fragmentation and hold potential as diagnostic biomarkers for male infertility.
