Decreased fecundity and sperm DNA methylation patterns

Jenkins, Timothy G.; Aston, Kenneth I.; Meyer, Tyson D.; Hotaling, James M.; Shamsi, Monis Bilal; Johnstone, Erica; Cox, Kyley J.; Stanford, Joseph B.; Porucznik, Christina A.; Carrell, Douglas T.

doi:10.1016/j.fertnstert.2015.09.013

Cited by 105 publications

(59 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A subset of 8 candidate genes, composed of the 5 most strongly regulated genes (ANKRD1, DNAJB1, HSPA6, HSPH1, RHOXF1) and 3 regulated genes that have been previously associated with human fertilization (HSPA1A; (29,30) and abnormal spermatogenesis (HSPA2, MSH5; (31,32), were selected for validation by qRT-PCR analysis.…”

Section: Identification Of Genes Regulated By Rhox Transcription Factorsmentioning

confidence: 99%

See 1 more Smart Citation

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

Borgmann

Tüttelmann²,

Dworniczak³

et al. 2016

Hum. Mol. Genet.

View full text Add to dashboard Cite

The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated with abnormal human sperm parameters. However, little is known about the molecular mechanism of RHOX function in humans. Using gene expression profiling, we identified genes regulated by members of the human RHOX gene cluster. Some genes were uniquely regulated by RHOXF1 or RHOXF2/2B, while others were regulated by both of these transcription factors. Several of these regulated genes encode we demonstrate how the X-linked RHOX gene cluster may function in normal human spermatogenesis and we provide evidence that it is impaired in human male fertility.

show abstract

Section: Identification Of Genes Regulated By Rhox Transcription Factorsmentioning

confidence: 99%

“…Very recently, aberrant methylation pattern of two closely related genes of HSPA1A, HSPA1B and HSPA1L, were associated with reduced fecundity (30). DNAJB1 belongs to the HSP40 family and encodes a protein in human spermatozoa (29) that has also been localized to the sperm head and tail of rodent spermatozoa (36).…”

mentioning

confidence: 99%

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

Borgmann

Tüttelmann²,

Dworniczak³

et al. 2016

Hum. Mol. Genet.

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that sperm DNA damage correlates with infertility, early pregnancy loss, defective embryogenesis, congenital malformations, genetic abnormalities and decreased fecundity and DNA sperm methylation pattern. (70) Till date majority of studies have focused on role of chromosomal abnormalities and analysis of nuclear genes for nucleotide alternations, which affect embryonic development. This study analyse role of oxidative stress, DNA damage and mitochondrial DNA variation in iRSA following spontaneous conception.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Spontaneous Abortion and Male Factors: An Overview

Imam¹,

Algaidi²,

Rahman³

2016

jemds

View full text Add to dashboard Cite

Recurrent miscarriage is three or more consecutive pregnancy loss before 20 weeks of gestation. Despite detailed investigation of couples experiencing RSA in 40 to 50% of cases, the aetiology cannot be ascertained and are termed Idiopathic Recurrent Spontaneous Abortions (iRSA). DISCUSSIONIn the clinical investigation of male partner of iRSA, semen analysis detailing the sperm parameters do not always reveal significant information that could assist the clinician in patient's treatment. Due to limited predictive potential of semen analysis, new markers with better diagnostic and prognostic characteristic and ability to efficiently predict adverse reproductive events are being investigated. The findings of these studies have reported oxidative stress associated with sperm DNA damage as a leading cause for lower conception rate after assisted conception techniques. These findings have also provided a new direction to the studies investigating molecular markers as free radicals, antioxidants and sperm DNA fragmentation. It has been suggested that these markers are more reliable than semen analysis in male infertility cases including male partners of couples experiencing iRSA. Further, these recent studies also suggest that oxidative stress and sperm DNA integrity may offer better potential to predict sperm reproductive capacity. CONCLUSIONThis review provides an in-depth understanding of iRSA, its causative factors, the clinical findings and the most preferred therapeutics that could assist to improve the pregnancy outcome in such cases.

show abstract

“…While some of these alterations are likely quite benign, it has been shown in recent studies that specific patterns of epigenetic alteration are associated with various abnormalities in sperm biology and have additionally been associated with subfertility [7][8][9]. These associations have driven research addressing the contribution of sperm DNA methylation and, more globally, all types sperm epigenetic alterations to the pathological processes of infertility and poor pregnancy outcomes [7,8]. This work has yielded a great degree of interesting findings.…”

Section: Introductionmentioning

confidence: 99%

“…Because of the dynamic nature of this mark in mammalian sperm, it is susceptible to alterations via cellular processes based on exposure to multiple modifiers including various toxins, pollutants, diet alterations, stress exposures and even age [4][5][6]. While some of these alterations are likely quite benign, it has been shown in recent studies that specific patterns of epigenetic alteration are associated with various abnormalities in sperm biology and have additionally been associated with subfertility [7][8][9]. These associations have driven research addressing the contribution of sperm DNA methylation and, more globally, all types sperm epigenetic alterations to the pathological processes of infertility and poor pregnancy outcomes [7,8].…”

Section: Introductionmentioning

confidence: 99%

Thermo Stability of DNA Methylation Marks in Human Sperm

Jenkins¹

2017

J Genet Genome Res

View full text Add to dashboard Cite

Shipping of various tissues, including sperm, for the purposes of diagnostic testing and/or collaborative scientific pursuits is commonly performed. While many sample attributes are largely stable during the shipping process regardless of shipping environment, some physical factors such as temperature, duration of storage and other handling conditions may affect certain features of these samples including a commonly assessed epigenetic mark, DNA methylation. Since any changes to these marks may drastically alter the outcome and interpretation of a study, it is imperative that handling conditions be carefully analyzed and validated for any assay. To date few studies have addressed the stability of this important regulatory epigenetic mark under various storage conditions in general, and none have explored these effects in the storage of sperm. In this study, sperm from 18 men was assessed for potential DNA methylation alterations resultant from exposure to high heat over varying amounts of exposure time. As liquid nitrogen is among the most commonly used storage conditions and generally very stable, we compared sample aliquots stored in liquid nitrogen compared to aliquots stored at 65 °C for varying durations. We assessed differential methylation globally, at specific regions, and at the single CpG level. High temperature exposure was not associated with methylation alterations, regardless of the duration of exposure. To confirm these findings, we performed unsupervised hierarchical clustering across the CpGs tiled on the array and found no clustering based on treatment group, rather, we found a strong clustering according to the individual from which each aliquot originated. These findings suggest that high temperature exposure is unlikely to affect sperm DNA methylation signatures significantly within the exposure times studied.

show abstract

Decreased fecundity and sperm DNA methylation patterns

Cited by 105 publications

References 28 publications

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

Recurrent Spontaneous Abortion and Male Factors: An Overview

Thermo Stability of DNA Methylation Marks in Human Sperm

Contact Info

Product

Resources

About