GLOBAL ANDROLOGY FORUM
GLOBAL ANDROLOGY FORUM
Publications
Sperm epigenetics landscape: correlation with embryo quality, reproductive outcomes, and offspring’s health
Sperm epigenetics landscape: correlation with embryo quality, reproductive outcomes, and offspring’s health.
Authors: Garrido N, Boitrelle F, Saleh, R, Durairajanayagam D, Colpi G, Agarwal A, Panminerva Medica
2023 June;65(2):166-78.
DOI: 10.23736/S0031-0808.23.04871-1
Preamble: Understanding Sperm Epigenetics
Epigenetics in male infertility involves changes that impact gene activity without altering the DNA sequence. For instance, DNA methylation modifications can affect sperm quality. Histone alterations during spermatogenesis impact the packaging of genetic material in sperm. Dysregulation of non-coding RNAs, like miRNAs, can lead to sperm function issues. These epigenetic changes can influence male fertility, affecting sperm function and potentially impacting fertility outcomes.
CAPSULE
Contributors: Nicolás Garrido, PhD (Valencia, Spain) and Sezgin Gunes, PhD (Samsun, Turkiye)
Various mechanisms govern epigenetic control in sperm, encompassing DNA methylation, histone modifications, and non-coding RNAs. These mechanisms play a pivotal role in cyclic DNA methylation changes, toggling specific genes on or off. In infertile males, some of these mechanisms are altered, compromising the maintenance of the necessary epigenetic pattern for optimal sperm function.
Proper methylation of both specific and imprinted paternal genes significantly influences sperm quality. During spermatogenesis, sperm chromatin undergoes modifications, replacing about 90-95% of histones with smaller protamines, compacting the paternal genome.
Non-coding RNAs like miRNAs, siRNAs, and piRNAs contribute to the transcriptional inactivation of spermatozoa. Aberrations in these processes can lead to fertilization issues, hindered embryo development, poorer outcomes in assisted reproductive technologies (ART), and health problems in offspring, despite normal semen parameters. Moreover, these factors can be transmitted to the offspring during meiosis.
Environmental and lifestyle factors such as alcohol consumption, diet, physical activity, and smoking can contribute to incorrect epigenetic markers, impacting sperm function and potentially affecting the health of future generations.
Discovering clinically significant epigenetic biomarkers has the potential to enhance the diagnosis of male fertility issues and facilitate the creation of precise treatments. This is because the epigenetic profile can be altered similarly to how external environmental factors affect it. Advancements in analytical technologies are providing fresh insights and a deeper comprehension of the epigenetic terrain, aiming to refine diagnoses and tailor therapies more effectively.
Take home message:
The available data indicates a connection between sperm epigenetic patterns and male fertility, as well as potential health risks for offspring. However, before implementing diagnostic tests or therapies based on this, more studies with proper design and adequate power are required to confirm and translate these findings into real-world applications.
Commentary:
Various techniques measure epigenetic changes in human spermatozoa from infertile men:
- DNA Methylation Analysis: Uses bisulfite sequencing or methylation-specific PCR toassess DNA methylation patterns in specific gene regions.
- Histone Modification Analysis: Investigates alterations in histone proteins through chromatin immunoprecipitation (ChIP) assays.
- Non-Coding RNA Profiling: Examines levels of regulatory non-coding RNAs (miRNAs, piRNAs) influencing gene expression.
- Epigenome-wide Association Studies (EWAS): Analyzes genome-wide epigenetic changes using high-throughput sequencing or microarrays.
These tests identify and quantify sperm epigenetic changes linked to male infertility. However, commercial epigenetic tests for human sperm are not yet available in clinical settings. While ongoing research explores epigenetic modifications in sperm, translating this into routine diagnostic tests is in the early stages. (Contributor: Ashok Agarwal, Director, Global Andrology Forum)
Nicolás Garrido: Short Biography
Dr. Nicolás Garrido
Director, Research Administration,
Research/Innovation, IVIRMA Global
Research Alliance
IVI Foundation Director
Edificio Biopolo – Instituto de
Investigación Sanitaria la Fe
Avenida Fernando Abril Martorell, 106 -
Torre A, Planta 1ª
46026 Valencia
IVI-RMA Global
Nicolas Garrido is the Director of IVI Foundation, and Director of Research Administration at IVI RMA Global, B.Sc. in Biology (University of Valencia) in 1997, followed by a Post-graduate Research Fellowship at the Department of Gynaecology, Heinrich-Heine University, Germany. He obtained his doctorate from the University of Valencia in 2001, Extraordinary Prize in 2002, and has a Master’s degree in Research Methodology: Design and Statistics in Health Sciences (Universitat Autònoma de Barcelon)) in 2009, in Science and Innovation Management in 2018 and in Project Management in 2020, (Universidad Politécnica de Valencia).
Nicolás was the Director of the Andrology Laboratory and Sperm Bank at the IVI University Institute in Valencia from 2000 till 2016 and led the IVI Teaching Program from 2004-2017. He is an Adjunct Professor at the University of Valencia, heading numerous research projects funded on male infertility, sperm physiology, sperm selection techniques, biomarkers of fertility, and statistics to measure ART success. He has authored 190 papers, 350 abstracts, and 80 chapters.
Nicolás serves as the Section Editor of Male Infertility at RBM Online, past Associate Editor for Fertility and Sterility, and Ad Hoc Reviewer of many journals in the field. He was the Past Coordinator of ESHRE Special Interest Group for Andrology.
Nicolás is a member of the GAF Statistical Expert Panel.
Sezgin Gunes, PhD: Short Biography
Professor Sezgin Gunes
Chair of Department of Medical Biology
and Molecular Genetics
Faculty of Medicine
Teaching fellow in Department of
Multidisciplinary Molecular Medicine
Graduate Institute
Ondokuz Mayis University, Atakum
55139 Samsun, Turkiye
Sezgin Gunes is a senior medical biologist and a Professor of Molecular Genetics at Ondokuz Mayis University, Turkiye. She teaches molecular biology and genetics courses and the biology of reproductive systems and genetics of cancer to the medical faculty students, M.Sc., and PhD students.
Sezgin is actively involved in the supervision of postgraduate students. Her experience is based on clinical diagnostic and the basic science arenas. Her special research interests are on genetic and epigenetic mechanisms underlying common human diseases, especially male infertility and urological and gynecological malignancies.
Sezgin has over 100 peer-reviewed articles and book chapters in international academic books.
Dr. Sezgin serves as the Co-leader of Research team 10 and as Co-leader in Research Training cell.
Acknowledgement: Nicolás and Sezgin contributed to this week’s Management Special.
We are grateful for their remarkable support over the years.