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Review
. 2022 Jan;16(1):1-9.
doi: 10.22074/IJFS.2021.138499.1032.

Epigenetic Modifications, A New Approach to Male Infertility Etiology: A Review

Eisa Tahmasbpour Marzouni  1 , Hanieh Ilkhani  2 , Asghar Beigi Harchegani  3 , Hossein Shafaghatian  4 , Issa Layali  5 , Alireza Shahriary  6
Affiliations
Review

Epigenetic Modifications, A New Approach to Male Infertility Etiology: A Review

Eisa Tahmasbpour Marzouni et al. Int J Fertil Steril. 2022 Jan.

Abstract

Recent studies have indicated that epigenetic alterations are critical for normal function and development of spermatozoa during the fertilization process. This review will focus on the latest advances in epigenome profiling of the chromatin modifications during sperm development, as well as the potential roles of epigenetic mechanisms in the context of male infertility. In this review, all data were collected from published studies that considered the effect of epigenetic abnormalities on human spermatogenesis, sperm parameters quality, fertilization process, embryo development and live births. The database PubMed was searched for all experimental and clinical studies using the Keywords "epigenetic modifications", "male infertility", "spermatogenesis", "embryo development" and "reproductive function". Post-translational modifications of histone, DNA methylations and chromatin remodeling are among the most common forms of epigenetic modifications that regulate all stages of spermatogenesis and fertilization process. Incorrect epigenetic modifications of certain genes involved in the spermatogenesis and sperm maturation may be a main reason of male reproductive disorder and infertility. Most importantly, abnormal patterns of epigenetic modifications or transgenerational phenotypes and miRNAs expression may be transmitted from one generation to the next through assisted reproductive techniques (ART) and cause an increased risk of birth defects, infertility and congenital anomalies in children. Epigenetic modifications must be considered as a one of the main factors of unexplained male infertility etiology. Due to high risk of transmitting incorrect primary imprints to offspring, there is a need for more research into epigenetic alterations in couples who benefit of ART support.

Keywords: Epigenetics; Male Infertility; Reproductive Function; Sperm.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig.1
Fig.1
A schematic for the most common causes of male infertility. Male infertility is a multifactorial syndrome that is caused by multiple factors. Anatomical defects, endocrine deficiency, immunological defects, molecular defects and chromosomal aneuploidy, as well as environmental exposure to toxicants and lifestyle are the most common causes of male infertility. Unexplained infertility may be resulted from idiopathic factors such as oxide stress, over expression of ROS and unknown mutations. ROS; Reactive oxygen species, LH; Luteinizing hormone, FSH; Follicle-stimulating hormone, and AZF; Azoospermia factor.
Fig.2
Fig.2
The regulatory function of epigenetic modification in all stages of male reproduction. Epigenetic modifications (EPs) are involved in nearly all stages of the reproductive system, including, testicular cell development, germ cell differentiation, steroidogenesis, spermatogenesis, sperm maturation, fertilization, and embryo development.
Fig.3
Fig.3
The basic molecular mechanisms of epigenetic modifications. DNA methylation, histone modifications, chromatin remodeling and miRNA biogenesis are the main mechanisms of epigenetic modifications that regulate many physiological processes in various cells. DNA methylation occurrence in the CpG islands regulates expression of various spermatogenesis genes. Histone acetylation that reversibly occurs at lysine residues within the N-terminal tail increases the propensity for gene transcription and also modulates chromatin remodeling. Also, miRNAs biogenesis is regulated by epigenetic modifications such as DNA methylation. It plays a significant role in the numerous physiological processes, particularly spermatogenesis, sperm maturation and fertilization process.
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