-
Nature Communications Nov 2023The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive....
The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive. Here, we determined that maternal high-fat diet during pregnancy in mice impaired preservation of the ovarian primordial follicle pool in female offspring, which was concomitant with mitochondrial dysfunction of germ cells. Furthermore, this occurred through a reduction in maternal gut microbiota-related vitamin B1 while the defects were restored via vitamin B1 supplementation. Intriguingly, vitamin B1 promoted acetyl-CoA metabolism in offspring ovaries, contributing to histone acetylation and chromatin accessibility at the promoters of cell cycle-related genes, enhancement of mitochondrial function, and improvement of granulosa cell proliferation. In humans, vitamin B1 is downregulated in the serum of women with gestational diabetes mellitus. In this work, these findings uncover the role of the non-gamete transmission of maternal high-fat diet in influencing offspring oogenic fate. Vitamin B1 could be a promising therapeutic approach for protecting offspring health.
Topics: Pregnancy; Animals; Female; Mice; Humans; Ovarian Follicle; Ovary; Oogenesis; Diet, High-Fat
PubMed: 37973927
DOI: 10.1038/s41467-023-43261-8 -
Animal Reproduction 2023Paternal programming is the concept that the environmental signals from the sire's experiences leading up to mating can alter semen and ultimately affect the phenotype... (Review)
Review
Paternal programming is the concept that the environmental signals from the sire's experiences leading up to mating can alter semen and ultimately affect the phenotype of resulting offspring. Potential mechanisms carrying the paternal effects to offspring can be associated with epigenetic signatures (DNA methylation, histone modification and non-coding RNAs), oxidative stress, cytokines, and the seminal microbiome. Several opportunities exist for sperm/semen to be influenced during development; these opportunities are within the testicle, the epididymis, or accessory sex glands. Epigenetic signatures of sperm can be impacted during the pre-natal and pre-pubertal periods, during sexual maturity and with advancing sire age. Sperm are susceptible to alterations as dictated by their developmental stage at the time of the perturbation, and sperm and seminal plasma likely have both dependent and independent effects on offspring. Research using rodent models has revealed that many factors including over/under nutrition, dietary fat, protein, and ingredient composition (e.g., macro- or micronutrients), stress, exercise, and exposure to drugs, alcohol, and endocrine disruptors all elicit paternal programming responses that are evident in offspring phenotype. Research using livestock species has also revealed that sire age, fertility level, plane of nutrition, and heat stress can induce alterations in the epigenetic, oxidative stress, cytokine, and microbiome profiles of sperm and/or seminal plasma. In addition, recent findings in pigs, sheep, and cattle have indicated programming effects in blastocysts post-fertilization with some continuing into post-natal life of the offspring. Our research group is focused on understanding the effects of common management scenarios of plane of nutrition and growth rates in bulls and rams on mechanisms resulting in paternal programming and subsequent offspring outcomes. Understanding the implication of paternal programming is imperative as short-term feeding and management decisions have the potential to impact productivity and profitability of our herds for generations to come.
PubMed: 37700908
DOI: 10.1590/1984-3143-AR2023-0076 -
Clinical Epigenetics Aug 2023Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells....
BACKGROUND
Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking.
METHODS
We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7-50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure.
RESULTS
Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure.
CONCLUSION
Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
Topics: Male; Humans; DNA Methylation; Smoking; Tobacco Smoking; Epigenesis, Genetic; Asthma; Cytosine; Guanine; Chromosomal Proteins, Non-Histone
PubMed: 37649101
DOI: 10.1186/s13148-023-01540-7 -
Current Issues in Molecular Biology Jan 2024This review examines the complex interactions between maternal influenza infection, the immune system, and the neurodevelopment of the offspring. It highlights the... (Review)
Review
This review examines the complex interactions between maternal influenza infection, the immune system, and the neurodevelopment of the offspring. It highlights the importance of high-quality studies to clarify the association between maternal exposure to the virus and neuropsychiatric disorders in the offspring. Additionally, it emphasizes that the development of accurate animal models is vital for studying the impact of infectious diseases during pregnancy and identifying potential therapeutic targets. By drawing attention to the complex nature of these interactions, this review underscores the need for ongoing research to improve the understanding and outcomes for pregnant women and their offspring.
PubMed: 38248325
DOI: 10.3390/cimb46010023 -
JAMA Network Open Aug 2023Existing epidemiological evidence is equivocal as to whether paternal depression poses a consequent risk of depression in offspring; meta-analysis of findings can help... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Existing epidemiological evidence is equivocal as to whether paternal depression poses a consequent risk of depression in offspring; meta-analysis of findings can help inform preventative intervention efforts.
OBJECTIVE
To conduct a systematic review and meta-analysis of observational studies examining the association between paternal and offspring depression.
DATA SOURCES
Embase, PubMed, PsycINFO, Scopus, and Web of Science databases were searched between inception and December 2022.
STUDY SELECTION
The review included all observational studies that investigated the association between paternal and offspring depression and 10 606 studies were initially identified.
DATA EXTRACTION AND SYNTHESIS
This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The review protocol was prospectively registered in PROSPERO. Summary odds ratios (ORs) and 95% CIs were pooled using inverse variance weighted random effect meta-analysis. Subgroup and sensitivity analyses were performed.
MAIN OUTCOMES AND MEASURES
The main outcome of interest was offspring depression measured using recognized depression assessment tools.
RESULTS
Sixteen observational studies published between 2002 and 2021 were included, with a combined sample of 7 153 723 father-child dyads. A meta-analysis of these studies showed that paternal depression was associated with an increased risk of depression in offspring (OR, 1.42; 95% CI, 1.17-1.71). The risk was higher among offspring exposed to paternal depressive disorders (OR, 1.65; 95% CI, 1.28-2.12) than those exposed to depression as defined by a nonclinical symptom scale (OR, 1.12; 95% CI, 1.06-1.19). Sensitivity analysis revealed consistent pooled estimates ranging from 1.35 (95% CI, 1.12-1.62) to 1.45 (95% CI, 1.18-1.78).
CONCLUSIONS AND RELEVANCE
Paternal depression was associated with subsequent offspring depression. This finding shows the intergenerational transmission of mental health problems and suggests that mental health interventions benefit not only the patient but also the family as a whole, including both parents.
Topics: Male; Humans; Depression; Fathers; Parents
PubMed: 37585203
DOI: 10.1001/jamanetworkopen.2023.29159 -
Cell Research Nov 2023Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using...
Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using adult body size as the primary readout, we reveal that maternal rather than paternal age has an evolutionarily conserved effect on offspring adult traits in humans, Drosophila, and Caenorhabditis elegans. Elucidating the mechanisms of such effects in humans and other long-lived animals remains challenging due to their long life course and difficulties in conducting in vivo studies. We thus employ the short-lived and genetically tractable nematode C. elegans to explore the mechanisms underlying the regulation of offspring adult trait by maternal aging. By microscopic analysis, we find that old worms transmit aged mitochondria with a donut-like shape to offspring. These mitochondria are rejuvenated in the offspring's early life, with their morphology fully restored before adulthood in an AMPK-dependent manner. Mechanistically, we demonstrate that early-life mitochondrial dysfunction activates AMPK, which in turn not only alleviates mitochondrial abnormalities but also activates TGFβ signaling to increase offspring adult size. Together, our findings provide mechanistic insight into the ancient role of maternal aging in shaping the traits of adult offspring.
Topics: Animals; Humans; Adult; Aged; Caenorhabditis elegans; AMP-Activated Protein Kinases; Aging; Body Size; Mitochondria
PubMed: 37500768
DOI: 10.1038/s41422-023-00854-8 -
Evolution, Medicine, and Public Health 2024Mammalian pregnancy is characterized by a well-known suite of physiological changes that support fetal growth and development, thereby positively affecting both maternal... (Review)
Review
Mammalian pregnancy is characterized by a well-known suite of physiological changes that support fetal growth and development, thereby positively affecting both maternal and offspring fitness. However, mothers also experience trade-offs between current and future maternal reproductive success, and maternal responses to these trade-offs can result in mother-offspring fitness conflicts. Knowledge of the mechanisms through which these trade-offs operate, as well as the contexts in which they operate, is critical for understanding the evolution of reproduction. Historically, hormonal changes during pregnancy have been thought to play a pivotal role in these conflicts since they directly and indirectly influence maternal metabolism, immunity, fetal growth and other aspects of offspring development. However, recent research suggests that gut microbiota may also play an important role. Here, we create a foundation for exploring this role by constructing a mechanistic model linking changes in maternal hormones, immunity and metabolism during pregnancy to changes in the gut microbiota. We posit that marked changes in hormones alter maternal gut microbiome composition and function both directly and indirectly via impacts on the immune system. The gut microbiota then feeds back to influence maternal immunity and metabolism. We posit that these dynamics are likely to be involved in mediating maternal and offspring fitness as well as trade-offs in different aspects of maternal and offspring health and fitness during pregnancy. We also predict that the interactions we describe are likely to vary across populations in response to maternal environments. Moving forward, empirical studies that combine microbial functional data and maternal physiological data with health and fitness outcomes for both mothers and infants will allow us to test the evolutionary and fitness implications of the gestational microbiota, enriching our understanding of the ecology and evolution of reproductive physiology.
PubMed: 38288320
DOI: 10.1093/emph/eoae001 -
The Journal of Clinical Investigation Nov 2023In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently,...
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation-ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.
Topics: Humans; Male; Animals; Mice; Sperm Injections, Intracytoplasmic; Semen; Fertilization in Vitro; Infertility; Neoplasms
PubMed: 37966118
DOI: 10.1172/JCI170140 -
Neuroscience and Biobehavioral Reviews Oct 2023Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and... (Meta-Analysis)
Meta-Analysis Review
Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and adverse neurodevelopmental outcomes in the offspring, however with inconsistent results. We performed a systematic review and meta-analysis to evaluate associations between excessive or insufficient GWG and offspring's neurodevelopmental outcomes. Meta-analysis of these 23 studies using a random-effects model revealed associations between excessive GWG and neurodevelopmental disorders (ASD & ID & ADHD together: OR=1.12 [95% CI 1.06-1.19]), ASD (OR=1.18 [95% CI 1.08-1.29]), ADHD (OR=1.08 [95% CI 1.02-1.14]), ASD with ID (OR=1.15 [95% CI 1.01-1.32]), and ASD without ID (OR=1.12 [95% CI 1.06-1.19]). Insufficient GWG was associated with higher risk for ID (OR=1.14 [95% CI 1.03-1.26]). These results emphasize the significant impact, though of small effect size, of GWG across multiple neurodevelopmental disorders. It is important to note that these results do not establish causality. Other factors such as genetic factors, gene-environment interactions may confound the relationship between GWG and neurodevelopmental outcomes. To better understand the role of GWG in neurodevelopmental disorders, future studies should consider using genetically sensitive designs that can account for these potential confounders.
Topics: Pregnancy; Female; Humans; Gestational Weight Gain; Weight Gain; Neurodevelopmental Disorders; Body Mass Index
PubMed: 37573899
DOI: 10.1016/j.neubiorev.2023.105360