Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm

Zhao, Wenlong; Gu, Ni-Hao; Li, Zhengzheng; Wang, Guishuan; Cheng, C. Yan; Sun, Fei

doi:10.18632/aging.104061

Cited by 20 publications

(20 citation statements)

References 40 publications

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“…As such, we divided 69,964 cases into subgroups stratified by maternal age and maternal BMI individually in order to examine whether the association between paternal age and birth weight is stable. We found that when maternal age is in a normal range (25)(26)(27)(28)(29)(30)(31)(32)(33)(34), the infants of aging fathers are at a higher risk for LGA. A significantly elevated risks for LGA contributed by advanced paternal age was confirmed among a subgroup of normal-BMI women.…”

Section: Interpretationsmentioning

confidence: 73%

“…When considering the underlying mechanism of this phenomenon, previous research involving mouse models suggests that advanced paternal age could exert adverse metabolic effects on offspring by impairing glucose tolerance (34). One possible explanation is that aging exerts epigenetic changes in male sperm including methylation status and histone modifications which may be an explanation for its effect on an offspring's increased risk for metabolism health conditions (23).…”

Section: Interpretationsmentioning

confidence: 99%

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Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study

et al. 2021

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PurposeWhile it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation).MethodsA large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight.ResultsAdvanced paternal age was associated with a higher risk for a preterm birth [35–44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35–44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery.ConclusionsOur study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.

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Section: Interpretationsmentioning

confidence: 73%

Section: Interpretationsmentioning

confidence: 99%

Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study

et al. 2021

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“…For example, the level of sperm DNA methylation has a significant positive correlation with male reproductive capacity in striped bass ( Morone saxatilis ) [ 16 ] and sperm concentration and motility in humans [ 17 ]. There are many studies on DNA methylation profiles in mammalian sperm [ 18 , 19 , 20 , 21 , 22 ]. Abnormalities of DNA methylation caused by modifications in cytosine phosphate guanine (CpG) islands and shore regions result in increased susceptibility to disease, abnormalities and disorders in the offspring from more aged mice sperm [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Abnormalities of DNA methylation caused by modifications in cytosine phosphate guanine (CpG) islands and shore regions result in increased susceptibility to disease, abnormalities and disorders in the offspring from more aged mice sperm [ 23 ]. Mice sperm aging causes high risks of aberrant glucose metabolism and the development of autism spectrum disorders and behaviors in intergenerational and transgenerational offspring [ 18 ]. Sperm DNA methylation in mice has also shown to be responsive to abnormal/functioned physiology [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in Phenotypes and DNA Methylation of In Vitro Aging Sperm in Common Carp Cyprinus carpio

Cheng

Vechtova

Füssy

et al. 2021

IJMS

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The purpose of the current study was to analyze phenotypic and functional characteristics of common carp (Cyprinus carpio) spermatozoa during in vitro aging and to investigate whether global DNA methylation is affected by sperm aging. Milt was collected from five individual males, stored in vitro on ice in a refrigerator for up to 96 h post stripping (HPS) and used to fertilize eggs with intervals of 1, 24 and 96 h. Computer-assisted sperm analysis and a S3e Cell Sorter was employed to determine the spermatozoa phenotypic characteristics (motility, velocity, concentration and viability). In addition, pH and osmolality of the seminal fluid and the capacity of the spermatozoa to fertilize, hatching rate and health of the resulting embryos were examined at different aging times. Whole-genome bisulfite sequencing was used to compare the global and gene-specific DNA methylation in fresh and aged spermatozoa. The results demonstrated that spermatozoa aging in common carp significantly affects their performance and thus the success of artificial fertilization. The methylation level at the cytosine-phosphate-guanine (CpG) sites increased significantly with 24 HPS spermatozoa compared to the fresh group at 1 HPS and then decreased significantly at 96 HPS. A more detailed investigation of gene specific differences in the DNA methylation was hindered by incomplete annotation of the C. carpio genome in the public databases.

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“…In the last decade, studies on rodents identified APA as a risk factor for the occurrence of neurodevelopmental/neurological conditions as well as cardio-metabolic and immune disorders in offspring [11,[16][17][18][19][20][21][22][23].…”

Section: Postnatal Development Behavior and Health Of Mouse Offspring Conceived By Aged Fathersmentioning

confidence: 99%

Delayed parenthood and its influence on offspring health: what have we learned from the mouse model

Zacchini¹,

Sampino²,

Zietek³

et al. 2021

Biology of Reproduction

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Delayed parenthood is constantly increasing worldwide due to various socio-economic factors. In the last decade, a growing number of epidemiological studies have suggested a link between advanced parental age and an increased risk of diseases in the offspring. Also, poor reproductive outcome has been described in pregnancies conceived by aged parents. Similarly, animal studies showed that aging negatively affects gametes, early embryonic development, pregnancy progression and the postnatal phenotype of resulting offspring. However, how and to what extent parental age is a risk factor for the health of future generations is still subject to debate. Notwithstanding the limitation of an animal model, the mouse model represents a useful tool to understand not only the influence of parental age on offspring phenotype but also the biological mechanisms underlying the poor reproductive outcome and the occurrence of diseases in the descendants. The present review aims at i) providing an overview of the current knowledge from mouse model about the risks associated with conception at advanced age (e.g. neurodevelopmental and metabolic disorders), ii) highlighting the candidate biological mechanisms underlying this phenomenon, and iii) discussing on how murine-derived data can be relevant to humans.

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Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm

Cited by 20 publications

References 40 publications

Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study

Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study

Changes in Phenotypes and DNA Methylation of In Vitro Aging Sperm in Common Carp Cyprinus carpio

Delayed parenthood and its influence on offspring health: what have we learned from the mouse model

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