Sperm chromatin and DNA integrity, methyltransferase mRNA levels, and global DNA methylation in oligoasthenoteratozoospermia

Rahiminia, Tahereh; Yazd, Ehsan Farashahi; Fesahat, Farzaneh; Moein, Mohammad Reza; Mirjalili, Seyed Ali Mohamad; Talebi, Ali Reza

doi:10.5653/cerm.2018.45.1.17

Cited by 34 publications

(21 citation statements)

References 37 publications

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“…), in addition to significant changes in both histone modification and DNA methylation status (Rahiminia et al . ). Therefore, disruption of the testicular epigenetic status in F1 male offspring could provide one mechanism through which paternal transgenerational programming occurs.…”

Section: Discussionmentioning

confidence: 97%

“…N 6 -adenosine methylation (m 6 A) is the most prevalent modification to mammalian RNA and is regulated by a series of methyltransferases and demethylases (Yue et al 2015). In humans, increased expression of FTO, METTL3 and METTL14, as well as levels of m 6 A, have been identified in the sperm of infertile men (Yang et al 2016), in addition to significant changes in both histone modification and DNA methylation status (Rahiminia et al 2018). Therefore, disruption of the testicular epigenetic status in F1 male offspring could provide one mechanism through which paternal transgenerational programming occurs.…”

Section: Paternal Diet Alters F1 Testicular Epigenetic Statusmentioning

confidence: 99%

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Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

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Key points A low protein diet had minimal effects on paternal cardiovascular function or renin–angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin–angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1 male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin‐converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner. Abstract Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup‐optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin‐converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin–angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub‐optimal paternal nutrition on offspring cardiovascular well‐being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.

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Section: Discussionmentioning

confidence: 97%

Section: Paternal Diet Alters F1 Testicular Epigenetic Statusmentioning

confidence: 99%

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

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“…It is thought that semen parameters do not directly represent the status of sperm nuclei, as sperm with normal motility and morphology may have chromatin and/or DNA abnormalities [34]. Previous studies have found significant positive correlations between DNA fragmentation and CMA3 positivity in infertile men [27,28,35]. Moreover, protamine defects were associated with the fertilization rate in stimulated assisted reproduction cycles according to Bianchi et al [36] and Iranpour et al [37].…”

Section: Discussionmentioning

confidence: 99%

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Hamidian

Talebi

Fesahat

et al. 2020

Clin Exp Reprod Med

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Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n = 20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases. This is an Open Access article distributed under the terms of the Creative Commons AttributionNon-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.eCERM.org S Hamidian et al. The effect of vitamin C on sperm gene expression

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“…All types of cells have their own epigenetic profiles, 10 and the epigenetic profile of germ cells is even more special as it can be transferred to further generations 11 . Along with the aspect of transgenerational inheritance, the epigenetic status of spermatozoa is an important factor in fertility because recent studies have shown that spermatozoal DNA methylation patterns can be correlated with sperm quality 12 . Consequently, this can affect the outcome of in vitro fertilization (IVF) procedures in terms of abnormal embryogenesis and pregnancy rates 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

Štimpfel

Vrtačnik-Bokal

2020

Andrology

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Background DNA methylation patterns can show transgenerational inheritance and are influenced by lifestyle and environmental factors. It is suggested that these patterns can be changed by assisted reproductive technology. Objectives To evaluate the impact of two different sperm preparation methods, conventional density gradient centrifugation (DGC) vs. density gradient centrifugation followed by magnetic‐activated cell sorting (MACS) of non‐apoptotic spermatozoa, on sperm DNA methylation profile. Materials and methods We analyzed semen of patients included in our IVF treatment program. Half of the semen from each included patient was prepared for ICSI using the DGC method and the other half with DGC followed by MACS. The remaining samples were processed for DNA methylation analysis with reduced representation bisulfite sequencing (RRBS). In addition to the DNA methylation profile, we assessed the morphology and DNA fragmentation of spermatozoa. Results RRBS analysis revealed that the average genome‐wide methylation level was similar between both groups (DGC vs. MACS group) and ranged from 0.53 to 0.56. Furthermore, RRBS analysis identified 99 differentially methylated regions (DMRs) and 800 differentially methylated positions (DMPs). In the DGC group, 43 DMRs and 392 DMPs were hypermethylated whereas 56 DMRs and 408 DMPs were hypomethylated compared with those in the MACS group. When DMRs and DMPs were annotated to genes, 3 genes associated with imprinting were found: IGF2, PRDM16, and CLF4/BRUNOL4. The percentage of morphologically normal spermatozoa (MACS vs. DGC; 14.0 ± 10.8 vs. 13.2 ± 10.0; P = .335) and of spermatozoa with fragmented DNA of patients with RRBS analysis (22.9 ± 21.1% vs. 34.4 ± 21.2; P = .529) were also similar between groups. Discussion and Conclusion Although the average genome‐wide level of sperm DNA methylation was similar in both sample groups, a distinctive number of methylation changes were observed in DMR and DMP levels. A larger number of samples should be analyzed and additional sperm preparation methods should be tested to confirm our findings.

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Sperm chromatin and DNA integrity, methyltransferase mRNA levels, and global DNA methylation in oligoasthenoteratozoospermia

Cited by 34 publications

References 37 publications

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

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