Effects of paternal overnutrition and interventions on future generations

In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.

A Genome-wide Association Study to Identify Candidate Genes for Metabolic Disorders in Offspring by in Vitro Fertilization

BackgroundIn vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. MethodsWe conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. ResultsWe identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. ConclusionsThe impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

A genome-wide association study to identify candidate genes for metabolic disorders in offspring by in vitro fertilization

Background: In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. Methods: We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. Results: We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. Conclusions: The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

A genome-wide association study to identify candidate genes for metabolic disorders in offspring by in vitro fertilization

In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, confirmed a conserved motif, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications

Gestational diabetes mellitus (GDM) is a common pregnancy complication which is normally diagnosed in the second trimester of gestation. With an increasing incidence, GDM poses a significant threat to maternal and offspring health. Therefore, we need a deeper understanding of GDM pathophysiology and novel investigation on the diagnosis and treatment for GDM. MicroRNAs (miRNAs), a class of endogenic small noncoding RNAs with a length of approximately 19-24 nucleotides, have been reported to exert their function in gene expression by binding to proteins or being enclosed in membranous vesicles, such as exosomes. Studies have investigated the roles of miRNAs in the pathophysiological mechanism of GDM and their potential as noninvasive biological candidates for the management of GDM, including diagnosis and treatment. This review is aimed at summarizing the pathophysiological significance of miRNAs in GDM development and their potential function in GDM clinical diagnosis and therapeutic approach. In this review, we summarized an integrated expressional profile and the pathophysiological significance of placental exosomes and associated miRNAs, as well as other plasma miRNAs such as exo-AT. Furthermore, we also discussed the practical application of exosomes in GDM postpartum outcomes and the potential function of several miRNAs as therapeutic target in the GDM pathological pathway, thus providing a novel clinical insight of these biological signatures into GDM therapeutic approach.

Non-genetic inheritance of environmental exposures: a protocol for a map of systematic reviews with bibliometric analysis

Background Over the last few decades, we increasingly see examples of parental environmental experiences influencing offspring health and fitness. More recently, it has become clear that some non-genetic effects can be conferred across multiple generations. This topic has attracted research from a diversity of disciplines such as toxicology, biomedical sciences, and ecology, due to its importance for environmental and health issues, as well as ecological and evolutionary processes, with implications for environmental policies. The rapid accumulation of primary research has enabled researchers to perform systematic reviews (SRs), including meta-analyses, to investigate the generality of and sources of variation in non-genetic effects. However, different disciplines ask different questions and SRs can vary substantially in scope, quality, and terminology usage. This diversity in SRs makes it difficult to assess broad patterns of non-genetic effects across disciplines as well as determine common areas of interest and gaps in the literature. To clarify research patterns within the SR literature on non-genetic inheritance, we plan to create a map of systematic reviews as well as conduct bibliometric mapping (referred to as ‘research weaving’). We will address four key questions: first, what are the broad research patterns unifying the SR literature on non-genetic inheritance across disciplines? Second, are there discipline-specific research patterns, including terminology use, between disciplines? Third, how are authors of the SR literature connected? Fourth, what is the reliability of the SR literature? Methods We will systematically collect reviews within the SR ‘family’ that examine non-genetic inheritance arising from parental and ancestral environment by searching databases for journal articles and grey literature, as well as conducting backwards and forwards searching. Search hits will be double screened using ‘decision trees’ that represent the inclusion criteria. All relevant data elements on the review’s topic, as well as a critical appraisal of the review’s approach and reporting, will be extracted into Excel flat sheets. Bibliometric data will be directly extracted from Scopus. We will then query all relevant data elements to address our objectives and present outcomes in easily interpretable tables and figures, accompanied by a narrative description of results.

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

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.