ART and health: clinical outcomes and insights on molecular mechanisms from rodent studies

Feuer, Sky K.; Camarano, L.; Rinaudo, Paolo

doi:10.1093/molehr/gas066

Cited by 59 publications

(55 citation statements)

References 168 publications

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“…In men with oligoasthenoteratozoospermia, methylation was markedly reduced at all CpGs, reaching statistical significance in subgroups with a sperm concentration of <10x10 6 /ml. These findings suggest that abnormal DNA methylation-mediated genomic imprinting is associated with oligoasthenoteratozoospermia and oligozoospermia (100)(101)(102)(103)(104)(105)(106)(107).…”

Section: Dna Methylation and Male Infertilitymentioning

confidence: 81%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

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Section: Dna Methylation and Male Infertilitymentioning

confidence: 81%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Even with the successful implementation of these technologies, ART is associated with a number of complications, including a higher risk of congenital anomalies, hypertensive disorders of pregnancy, disorders of the placenta, preterm birth, low birth weight, perinatal mortality and small size for gestational age, imprinting disorders, among other problems presenting at birth, as well as later onset problems [5–8]. Animal models of ART with no underlying infertility, can exhibit analogous complications that have been described in ART children, suggesting that ART procedures are the source of these complications rather than reasons associated with infertility [9]. In this review, we discuss how ART procedures may impact epigenetic reprogramming coinciding with embryonic development and summarize the current epidemiological and experimental evidence suggesting ART procedures result in adverse postnatal cardiometabolic outcomes.…”

Section: Introductionmentioning

confidence: 99%

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Vrooman

Bartolomei

2017

Reproductive Toxicology

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Millions of children have been born worldwide though assisted reproductive technologies (ART). Consistent with the Developmental Origins of Health and Disease hypothesis, there is concern that ART can induce adverse effects, especially because procedures coincide with epigenetic reprogramming events. Although the majority of studies investigating the effects of ART have focused on perinatal outcomes, more recent studies demonstrate that ART-conceived children may be at increased risk for postnatal effects. Here, we present the current epidemiological evidence that ART-conceived children have detectable differences in blood pressure, body composition, and glucose homeostasis. Similar effects are observed in the ART mouse model, which have no underlying infertility, suggesting that cardiometabolic effects are likely caused by ART procedures and not due to reasons related to infertility. We propose that the mouse system can, consequently, be used to adequately study, modify, and improve outcomes for ART children.

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“…Murine studies have indicated that the relatively transient nutritional stresses that IVF places on the growing embryo can result in a considerable change in gene expression, metabolism, and growth trajectory (8)(9)(10), persisting into adulthood (11)(12)(13)(14). Although the mechanisms are likely many, the increased incidence of random epigenetic errors, including changes in imprinted genes, has been proposed (10,15).…”

mentioning

confidence: 99%