Systematic Reviews
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World J Med Genet. Oct 27, 2022; 10(2): 7-21
Published online Oct 27, 2022. doi: 10.5496/wjmg.v10.i2.7
Epigenetics in the etiology and management of infertility
Tajudeen Olanrewaju Yahaya, Danlami M Bashar, Esther O Oladele, Ja'afar Umar, Daniel Anyebe, Abdulrazaq Izuafa
Tajudeen Olanrewaju Yahaya, Ja'afar Umar, Abdulrazaq Izuafa, Department of Biological Sciences, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
Danlami M Bashar, Department of Microbiology, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
Esther O Oladele, Biology Unit, Distance Learning Institute, University of Lagos, Lagos State 23401, Nigeria
Daniel Anyebe, Department of Biochemistry and Molecular Biology, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
Author contributions: Yahaya TO conceptualized, performed the literature search, article writing and correspondence; Bashar DM performed the literature search and article writing; Oladele EO and Umar J performed article writing and proofreading; Anyebe D and Izuafa I performed article sorting; all authors proofread, and approved the final manuscript.
Conflict-of-interest statement: All the authors declared no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist. A structured abstract is provided on page 2; rationale and objectives of the study are provided in the introduction on page 5; methodology, which described eligibility criteria for article selection, databases searched, and article selection criteria, is reported on page 5; results are synthesized on page 6; and a discussion of results is provided on pages 6–19.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tajudeen Olanrewaju Yahaya, PhD, Associate Professor, Department of Biological Sciences, Federal University Birnin Kebbi, Along Kalgo/Bunza Road, Birnin Kebbi, Kebbi State 23401, Nigeria.
Received: March 5, 2022
Peer-review started: March 5, 2022
First decision: June 16, 2022
Revised: June 28, 2022
Accepted: October 12, 2022
Article in press: October 12, 2022
Published online: October 27, 2022

Epigenetic disruptions have been implicated in some cases of infertility and can serve as therapeutic targets. However, the involvement of epigenetics in infertility has not received adequate attention.


This study aimed to determine the epigenetic basis of infertility in order to enhance public knowledge.


Relevant articles on the subject were collected from PubMed, RCA, Google Scholar, SpringerLink, and Scopus. The articles were pooled together and duplicates were removed using Endnote software.


Available information shows that epigenetic mechanisms, mainly DNA methylation, histone modification, and microRNA interference are necessary for normal gametogenesis and embryogenesis. As a result, epigenetic disruptions in genes that control gametogenesis and embryogenesis, such as DDX3X, ADH4, AZF, PLAG1, D1RAS3, CYGB, MEST, JMJD1A, KCNQ1, IGF2, H19, and MTHFR may result in infertility. Aberrant DNA methylation during genomic imprinting and parental epigenetic mark erasures, in particular, may affect the DNA epigenomes of sperm and oocytes, resulting in reproductive abnormalities. Histone epigenetic dysregulation during oocyte development and histone-protamine replacement in the sperm may also cause reproductive abnormalities. Furthermore, overexpression or repression of certain microRNAs embedded in the ovary, testis, embryo, as well as granulosa cells and oocytes may impair reproduction. Male infertility is characterized by spermatogenesis failure, which includes oligozoospermia, asthenozoospermia, and teratozoospermia, while female infertility is characterized by polycystic ovary syndrome. Some epigenetic modifications can be reversed by deactivating the regulatory enzymes, implying that epigenetic reprogramming could help treat infertility in some cases. For some disorders, epigenetic drugs are available, but none have been formulated for infertility.


Some cases of infertility have an epigenetic etiology and can be treated by reversing the same epigenetic mechanism that caused it. As a result, medical practitioners are urged to come up with epigenetic treatments for infertility that have an epigenetic cause.

Keywords: DNA methylation, Gametogenesis, Infertility, Polycystic ovary syndrome, Oligozoospermia, Teratozoospermia

Core Tip: This article reviews the role of epigenetics in the etiology of infertility, which can be used as a therapeutic target. Some cases of infertility are due to epigenetic disruptions, and this is probably the cause of unknown etiology in some cases of infertility. However, there is little awareness on this subject, hindering its application in mainstream medicine.