Epigenetic Mechanisms of Paternal Stress in Offspring Development and Diseases

Xu, Xingyun; Miao, Zhigang; Sun, Miao; Wan, Bo

doi:10.1155/2021/6632719

Cited by 22 publications

(17 citation statements)

References 101 publications

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“…Recent studies suggested that maternal and paternal exercise may affect the metabolic health in adult offspring (Zheng et al, 2020) and sperm epigenome can be epigenetically modified by environmental factors and the health of the offspring can be affected by the transgenerational passage of the modified epigenome (Xu et al, 2021). Metformin may regulate epigenetic modifications (Menendez, 2020) and these have been considered as one of the mechanisms explaining the beneficial effects of metformin on the prevention of cancer (Cuyàs et al, 2021) and aging (Menendez, 2020).…”

Section: Metformin May Adversely Affect Sexual Functionsmentioning

confidence: 99%

Metformin’s effects on varicocele, erectile dysfunction, infertility and prostate-related diseases: A retrospective cohort study

Tseng

2022

Front. Pharmacol.

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Objectives: To investigate the risk of varicocele, erectile dysfunction (ED), infertility, prostatitis, benign prostate hyperplasia (BPH) and prostate cancer associated with metformin use.Materials and methods: A total of 261,838 males, mean age 52.39 years (SD: 11.39), with a new-onset type 2 diabetes mellitus in 1999–2009 were identified from Taiwan’s National Health Insurance. Among them, 175,171 were metformin initiators [metformin (+)] and 86,667 were non-metformin initiators [metformin (−)] in the initial 12-month prescriptions of antidiabetic drugs. Follow-up started after the initial 12-month prescriptions. Outcomes were followed up until 31 December 2011. Intention-to-treat (ITT) and per-protocol (PP) hazard ratios comparing metformin (+) to metformin (−) were estimated by Cox regression incorporated with the inverse probability of treatment-weighting using propensity scores.Results: The median follow-up time ranged 5.55–6.82 years in metformin (−) and 4.36–5.17 years in metformin (+) for different outcomes in ITT analyses. The respective median follow-up time in PP analyses ranged 2.20–2.61 years in metformin (−) and ranged 3.99–4.65 years in metformin (+). In the ITT analyses, for metformin (−), the incidence rates (per 100,000 person-years) of varicocele, ED, infertility, prostatitis, BPH and prostate cancer were 26.42, 455.89, 22.82, 590.23, 4226.19, and 141.69, respectively; and the respective incidence rates for metformin (+) were 25.65, 488.10, 32.60, 510.30, 3685.66, and 116.57. The hazard ratios (95% confidence intervals) comparing metformin (+) to metformin (−) in the ITT analyses were 0.960 (0.784–1.174) for varicocele, 1.077 (1.026–1.130) for ED, 1.368 (1.116–1.676) for infertility, 0.887 (0.849–0.927) for prostatitis, 0.883 (0.868–0.899) for BPH and 0.878 (0.802–0.961) for prostate cancer. The hazard ratios for the respective outcomes in the PP analyses were 0.845 (0.662–1.078), 1.350 (1.264–1.441), 1.396 (1.078–1.808), 0.800 (0.756–0.846), 0.875 (0.855–0.895), and 0.613 (0.548–0.686).Conclusion: Metformin use in patients with type 2 diabetes mellitus is associated with a neutral effect on varicocele, a higher risk of sexual dysfunction (ED and infertility) and a reduced risk of prostate-related health (prostatitis, BPH and prostate cancer).

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Section: Metformin May Adversely Affect Sexual Functionsmentioning

confidence: 99%

Metformin’s effects on varicocele, erectile dysfunction, infertility and prostate-related diseases: A retrospective cohort study

Tseng

2022

Front. Pharmacol.

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“…Furthermore, paternal stress can impact the health of offspring through genetic inheritance, particularly by altering the sperm epigenome. This includes modifications in DNA methylation, histone modifications, sncRNAs, and sncRNAs‐associated alterations 49 . Importantly, paternal stress might also indirectly affect the health outcomes of offspring by influencing maternal investment in their offspring 50 .…”

Section: Discussionmentioning

confidence: 99%

“…This includes modifications in DNA methylation, histone modifications, sncRNAs, and sncRNAsassociated alterations. 49 Importantly, paternal stress might also indirectly affect the health outcomes of offspring by influencing maternal investment in their offspring. 50 However, these mechanistic pathways are less well established in humans and should be explored further to establish the first instigators of immune activation in diverse maternal states.…”

Section: F I G U R Ementioning

confidence: 99%

Early exposure to maternal stress and risk for atopic dermatitis in children: A systematic review and meta‐analysis

Ai,

Huang,

Zhu

2024

Clinical & Translational All

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BackgroundThe incidence of atopic dermatitis (AD) in children is increasing. Early exposure to stress factors may be associated with the AD development. This study aimed to summarize studies that reported an association between stress exposure and AD development in later life.Methods and findingsA comprehensive literature search was performed using online databases (PubMed, EMBASE, PsycINFO, and Web of Science) for articles published up to May 1, 2023. Eligible studies were screened and selected based on the inclusion criteria. We incorporated cohort or case‐control studies published in English which explored the relationship between stress experienced by parents or children and AD. The pooled odds ratio (OR) was calculated according to the type of stress using a random‐effects model. Twenty‐two studies were included. AD was related to maternal distress (OR 1.29, 95% Confidence Interval [CI]: 1.13–1.47), maternal anxiety (OR 1.31, 95% CI: 1.18–1.46), and negative life events (OR 2.00, 95% CI: 1.46–2.76). Maternal depression during pregnancy was associated with AD (OR 1.21, 95% CI: 1.09–1.33), whereas no significant association was found for postpartum depression. Research on stress experienced by paternal or children is scare.ConclusionsEarly maternal stress may potentially elevate the risk of AD in their offspring. Importantly, rigorously designed studies are required to corroborate the link between maternal stress and AD in children. These studies should aim to gather insights about the impact of stress during specific trimesters of pregnancy, postnatal stress, and paternal stress, and to identify potential prevention strategies.

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“…Epigenetic modification, especially DNA methylation, plays an important role in determining the differentiation potential of mammalian cells and ensuring the normal development. The methylation changes of a specific gene in the parent sperm cannot directly lead to the defective phenotype of the offspring, but it is undeniable that the methylation of CpG islands affects a series of cascade gene expressions, resulting in abnormal gene crossover network expression [68]. The potential roles of epigenetic processes in the progress of sperm function and male fertilization were studied by many researchers.…”

Section: Aberrant Sperm's Epigenetic Modificationsmentioning

confidence: 99%

“…Sperm histones are involved in chromatin conformation and gene expression through various posttranslational modifications. Modification of sperm histones may influence the large scale demethylation wave after fertilization, altering the expression of offspring genes [68].…”

Section: Disrupted Sperm's Histone Marksmentioning

confidence: 99%

Epigenetics in Male Infertility

Hassani¹,

Al-Jumaily²,

Lafta³

2022

Male Reproductive Anatomy

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Male infertility is a complex medical condition, in which epigenetic factors play an important role. Epigenetics has recently gained significant scientific attention since it has added a new dimension to genomic and proteomic research. As a mechanism for maintaining genomic integrity and controlling gene expression, epigenetic modifications hold a great promise in capturing the subtle, yet very important, regulatory elements that might drive normal and abnormal sperm functions. The sperm’s epigenome is known to be marked by constant changing over spermatogenesis, which is highly susceptible to be influenced by a wide spectrum of environmental stimuli. Recently, epigenetic aberrations have been recognized as one of the causes of idiopathic male infertility. Recent advances in technology have enabled humans to study epigenetics role in male infertility.

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Epigenetic Mechanisms of Paternal Stress in Offspring Development and Diseases

Cited by 22 publications

References 101 publications

Metformin’s effects on varicocele, erectile dysfunction, infertility and prostate-related diseases: A retrospective cohort study

Metformin’s effects on varicocele, erectile dysfunction, infertility and prostate-related diseases: A retrospective cohort study

Early exposure to maternal stress and risk for atopic dermatitis in children: A systematic review and meta‐analysis

Epigenetics in Male Infertility

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