N6-Methyladenosine and 5-Methylcytosine Epitranscriptomic Regulation of Male Reproduction and Fertility.
5 affiliations
- 1Reproductive Endocrinology and Infertility Section, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA.
- 2Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA.
- 3Center for Biotechnology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates.
- 4Department of Medical Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates.
- 5Department of Obstetrics and Gynecology, Sheik Shakhbout Medical City, Abu Dhabi P.O. Box 127788, United Arab Emirates.
Abstract
Functional spermatozoa production depends on spermatogenesis, a complex developmental process that requires precise regulation of gene expression at multiple levels. Although considerable progress has been made in understanding the transcriptional and epigenetic mechanisms governing germ cell development, post-transcriptional regulation mediated by RNA modifications has recently emerged as an important component of male fertility regulation. Epitranscriptomics, the study of chemical RNA modifications and their associated regulatory proteins, has revealed diverse roles for RNA modifications in spermatogenesis, sperm maturation, fertilization, and early embryonic development. Among more than 170 RNA modifications identified to date, N⁶-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C) are well characterized in the male reproductive system. Distinct groups of regulatory proteins function to deposit, remove, and recognize these modifications, thereby controlling RNA fate and metabolism. Functional studies in genetic knockout animal models show that disrupting key epitranscriptomic regulators contributes to abnormal germ cell development at multiple developmental stages. Notably, adverse environmental exposure reprograms the germ cell epitranscriptome, leading to abnormal spermatogenesis and male infertility. In light of recent advances, this narrative review summarizes current progress in male fertility, with particular emphasis on m⁶A and m⁵C RNA modifications. Finally, it outlines future perspectives on RNA modification studies in male fertility. Deeper mechanistic insights into male infertility can contribute to the development of new targeted therapies.
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BibTeX
@article{salih2026n6methyladenosine,
title = {{N6-Methyladenosine and 5-Methylcytosine Epitranscriptomic Regulation of Male Reproduction and Fertility.}},
author = {Sana M Salih and Ayman Al-Hendy and Qiwei Yang},
journal = {Biology},
year = {2026},
month = sep,
doi = {10.3390/biology15191678},
url = {https://europepmc.org/article/MED/42883351},
note = {CC BY},
}
RIS
TY - JOUR
TI - N6-Methyladenosine and 5-Methylcytosine Epitranscriptomic Regulation of Male Reproduction and Fertility.
AU - Sana M Salih
AU - Ayman Al-Hendy
AU - Qiwei Yang
PY - 2026
DA - 2026/09/22
JO - Biology
DO - 10.3390/biology15191678
UR - https://europepmc.org/article/MED/42883351
AB - Functional spermatozoa production depends on spermatogenesis, a complex developmental process that requires precise regulation of gene expression at multiple levels. Although considerable progress has been made in understanding the transcriptional and epigenetic mechanisms governing germ cell development, post-transcriptional regulation mediated by RNA modifications has recently emerged as an important component of male fertility regulation. Epitranscriptomics, the study of chemical RNA modifications and their associated regulatory proteins, has revealed diverse roles for RNA modifications in spermatogenesis, sperm maturation, fertilization, and early embryonic development. Among more than 170 RNA modifications identified to date, N⁶-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C) are well characterized in the male reproductive system. Distinct groups of regulatory proteins function to deposit, remove, and recognize these modifications, thereby controlling RNA fate and metabolism. Functional studies in genetic knockout animal models show that disrupting key epitranscriptomic regulators contributes to abnormal germ cell development at multiple developmental stages. Notably, adverse environmental exposure reprograms the germ cell epitranscriptome, leading to abnormal spermatogenesis and male infertility. In light of recent advances, this narrative review summarizes current progress in male fertility, with particular emphasis on m⁶A and m⁵C RNA modifications. Finally, it outlines future perspectives on RNA modification studies in male fertility. Deeper mechanistic insights into male infertility can contribute to the development of new targeted therapies.
SN - 2079-7737
ER -