Epigenetics and its role in male infertility
Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.Journal of Assisted Reproduction and Genetics (Impact Factor: 1.72). 01/2012; 29(3):213-23. DOI: 10.1007/s10815-012-9715-0
Male infertility is a common and complex problem affecting 1 in 20 men. Despite voluminous research in this field, in many cases, the underlying causes are unknown. Epigenetic factors play an important role in male infertility and these have been studied extensively. Epigenetic modifications control a number of processes within the body, but this review will concentrate on male fertility and the consequences of aberrant epigenetic regulation/modification. Many recent studies have identified altered epigenetic profiles in sperm from men with oligozoospermia and oligoasthenoteratozoospermia. During gametogenesis and germ cell maturation, germ cells undergo extensive epigenetic reprogramming that involves the establishment of sex-specific patterns in the sperm and oocytes. Increasing evidence suggests that genetic and environmental factors can have negative effects on epigenetic processes controlling implantation, placentation and fetal growth. This review provides an overview of the epigenetic processes (histone-to-protamine exchange and epigenetic reprogramming post-fertilization), aberrant epigenetic reprogramming and its association with fertility, possible risks for ART techniques, testicular cancer and the effect of environmental factors on the epigenetic processes.
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[Show abstract] [Hide abstract] ABSTRACT: Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. Copyright © 2015 Elsevier Ltd. All rights reserved.
- "A similar study carried out by Kang and co-workers did not show either altered hatching rates of medaka couples or progeny malformations when exposing breeders to a range of BPA from 837 to 3129 mg/L BPA near the mating time (Kang et al., 2002). Taking into account that zebrafish spermatogenesis lasts 21 days at 20 C (Schulz et al., 2010), our period of exposure affected the early stages of spermatogenesis (from spermatogonia to spermatid) potentially compromising genome, epigenome and transcriptome of spermatozoa (Dada et al., 2012). The lack of impact on the progeny development of medaka when exposing after spermiogenesis has been completed is, therefore, another evidence of the stage-specific effects caused by BPA. "
[Show abstract] [Hide abstract] ABSTRACT: Is the risk of hospital admission or outpatient contact for mental disorders increased in children born to women with fertility problems compared with children born to women without fertility problems? We found an increased risk of hospital admission or outpatient contact for mental disorders in children born to women with fertility problems. Few studies have investigated the risk of mental disorders in children born after fertility treatment and although some studies have pointed to an increased risk, others found no association. The inconsistent results may be due to methodological constraints in many previous studies, including small sample size and short follow-up, resulting in imprecise risk estimates and lack of information on risk patterns of mental disorders in adulthood. This nationwide retrospective register-based cohort study included all 2 412 721 children born in Denmark between 1969 and 2006. All children were followed from date of birth until date of hospital contact for a mental disorder, date of emigration, date of death or 31 December 2009, whichever occurred first. Information concerning maternal fertility status for all children in the cohort was obtained by linkage to the Danish Infertility Cohort, which contains data on nearly all women with fertility problems in Denmark since 1963. A total of 124 269 (5%) children were born to women with fertility problems and 2 288 452 (95%) to women without fertility problems. To identify children hospitalized for a mental disorder, the cohort was linked to the Danish Psychiatric Central Research Registry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk of hospital admission or outpatient contact for various groups of mental disorders, including any mental disorder and all 11 main discharge diagnostic groups, classified according to the International Classification of Diseases, version 10. During a mean follow-up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to hospital or had an outpatient contact for a mental disorder. Children born to women with fertility problems had a significantly higher risk of any mental disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective) disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention-deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with children born to women without fertility problems. The risk estimates did not change markedly when analyses were performed separately for mental disorders diagnosed during childhood (0-19 years) and in young adulthood (20-40 years). The true risk of mental disorders may be somewhat underestimated, as only severe disorders requiring hospital admission or outpatient contact were considered as events. Furthermore, we could not determine whether the increased risks observed were due to factors related to the underlying infertility or to fertility treatment procedures. This is the first report on mental disorders in adulthood among children born to women with fertility problems. Furthermore, we have assessed the risk of several severe mental disorders not previously studied (e.g. neurotic, stress-related and somatoform disorders and disorders of adult personality and behaviour). These important findings should be investigated further in large epidemiological studies designed to differentiate between factors related to fertility treatment and to the underlying infertility. The study was supported by internal funding from the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center. All authors report no conflicts of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: email@example.com.
- "It is still unclear, however, whether any epigenetic effects seen after fertility treatment are due to the treatment or to the infertility. It has been suggested that women with fertility problems are more likely to generate gametes with epigenetic modifications (Giacobino and Chaillet, 2004) and that some subfertile couples have a genetic predisposition to epigenetic instability (Dada et al., 2012 ). Furthermore, steroid hormone imbalance , which is central to certain types of infertility (Lyall et al., 2013), may affect the risk of mental disorders by affecting epigenetic fetal programming (Jessen and Auger, 2011; Nugent and McCarthy, 2011; Morgan and "
[Show abstract] [Hide abstract] ABSTRACT: Sperm DNA fragmentation varies between individuals and is more pronounced with increased patient age and time after sperm donation. The intensification of DNA fragmentation depends on the balance of the oxidoreductive system, which is regulated mainly by two enzymes – superoxide dismutase (SOD) and catalase. The objective of this study was to determine the relationship between sperm DNA fragmentation dynamics, fertility and seminal SOD and catalase activity. The study was conducted in 2013 and 2014 at the Non-Public Health Care Unit 'Ovum Reproduction and Andrology' in Lublin, Lublin, Poland, and covered 218 men aged 25–35 (85 fertile and 133 patients treated for infertility). Percentage of fragmented DNA was measured in a modified chromatin dispersion test at four time points after sperm donation (t = 0, 3, 6, 12 h). SOD and catalase activities were determined spectrophotometrically. We confirmed that the activity of SOD in the seminal plasma of men with reproductive disorders was lower compared with fertile men. Conversely, no significant correlations were found between fertility and catalase activity. Sperm DNA of infertile males was initially more fragmented than fertile male sperm DNA. SOD and catalase activity did not correlate with the degree of DNA fragmentation in fertile men. In men with reproductive disorders, the rate of DNA fragmentation was slow within first 3 h after sperm donation and then increased between 6 and 12 h. In this group of infertile men, those with higher SOD activity had a lower DNA fragmentation index (DFI) after 12 h, and a reduced rate of intensity of fragmentation from 6 to 12 h. Alternatively, higher catalase activity among men treated for infertility was accompanied by higher initial DFI and higher rate of DNA fragmentation from 6 to 12 h. These results highlight the importance of determining a proper time window between sperm donation and procedures of assisted reproductive technology.
- "Thus, the time taken from donating semen until its usage in assisted reproductive technology (ART) procedures is critical for their success. The quality of the male genetic material , which depends, among other things, on the degree of fragmentation of nuclear DNA, will have a direct impact on the embryo development and the health of future generations (Borini et al., 2006; Dada et al., 2012 "