Developmental, cytogenetic and epigenetic consequences of removing complex proteins and adding melatonin during in vitro maturation of bovine oocytes DOI Creative Commons
D. Tutt,

Gizem Guven-Ates,

Wing Yee Kwong

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 23, 2023

Background In vitro maturation (IVM) of germinal vesicle intact oocytes prior to in fertilization (IVF) is practiced widely animals. human assisted reproduction it generally reserved for fertility preservation or where ovarian stimulation contraindicated. Standard practice incorporates complex proteins (CP), the form serum and/or albumin, into IVM media mimic follicle environment. However, undefined nature CP, together with batch variation and ethical concerns regarding their origin, necessitate development more defined formulations. A known component follicular fluid, melatonin, has multifaceted roles including that a metabolic regulator antioxidant. certain circumstances can enhance oocyte maturation. At this stage development, germinal-vesicle prone aneuploidy epigenetic dysregulation. Objectives To determine developmental, cytogenetic consequences removing CP melatonin during bovine IVM. Materials methods The study comprised 2 x factorial arrangement comparing (i) inclusion exclusion (ii) addition (100 nM) omission Cumulus-oocyte complexes (COCs) were retrieved from stimulated cycles. Following IVF, putative zygotes cultured Day 8 standard media. RNAseq was performed on isolated cumulus cells, analyses (SNP-based algorithms) trophectoderm DNA methylation analysis (reduced representation bisulfite sequencing) cells inner-cell mass. Results Removal led modest reductions blastocyst whilst added beneficial presence but detrimental absence CP. composition did not affect incidence chromosomal abnormalities cumulus-cell transcript expression indicated altered metabolism (primarily lipid) COCs. These effects preceded establishment distinct signatures several days later expanded hatching blastocysts. Conclusions findings highlight importance lipid, particularly sterol, by COC They lay foundation future studies seek develop chemically systems generation transferrable embryos are both cytogenetically epigenetically normal.

Language: Английский

Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development DOI Creative Commons
Ariane Lismer, Sarah Kimmins

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 14, 2023

Abstract Although more studies are demonstrating that a father’s environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought sperm exclusively contributed its genome to egg. More recently, association have shown various environmental exposures including poor diet, toxicants, stress, perturbed epigenetic marks in at important reproductive developmental loci were associated with offspring phenotypes. The cellular routes underlie how transmitted fertilization, resist reprogramming embryo, drive phenotypic changes only now beginning be unraveled. Here, we provide an overview of state field intergenerational paternal mammals present new insights into relationship between embryo development three pillars inheritance: chromatin, DNA methylation, non-coding RNAs. We evaluate compelling evidence sperm-mediated transmission retention embryo. Using landmark examples, discuss sperm-inherited regions may escape impact via implicate transcription factors, chromatin organization, transposable elements. Finally, link paternally functional pre- post-implantation Understanding factors will permit greater understanding related origins disease.

Language: Английский

Citations

78
Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice DOI Creative Commons
Jingwei Liu, Junchao Shi, Rebecca Hernandez

et al.

Environment International, Journal Year: 2023, Volume and Issue: 172, P. 107769 - 107769

Published: Jan. 23, 2023

Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure cardiometabolic mortality in humans, societal costs ∼ $39 billion/year or more. We recently demonstrated that several widely used EDCs increase disease appropriate mouse models. In addition affecting adult health, parental has also been shown cause metabolic disorders, including obesity and diabetes, offspring. While most studies have focused on impact maternal EDC offspring's little known about effects paternal exposure. current study, we investigated adverse a but understudied phthalate, dicyclohexyl (DCHP) health F1 F2 offspring mice. Paternal DCHP led exacerbated insulin resistance impaired signaling without diet-induced obesity. previously showed sperm small non-coding RNAs tRNA-derived (tsRNAs) rRNA-derived (rsRNAs) contribute intergenerational transmission paternally acquired disorders. Using novel PANDORA-seq, revealed can lead tsRNA/rsRNA landscape changes were undetected by traditional RNA-seq, which may DCHP-elicited effects. Lastly, found sex-specific transgenerational elicited glucose intolerance female descendants. Our results suggest phthalates their These findings our understanding etiology human diseases originating from chemical-elicited

Language: Английский

Citations

44
Microplastics exposure: implications for human fertility, pregnancy and child health DOI Creative Commons

Rewa E. Zurub,

Yusmaris Cariaco, Michael G. Wade

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Plastics found in our everyday environment are becoming an increasing concern for individual and population-level health, the extent of exposure potential toxic effects these contaminants on numerous human organ systems clear. Microplastics (MPs), tiny plastic particles, appear to have many same biological as their precursors compounded effect accumulation different organs. Recently, microplastic was observed placenta, raising important questions related health pregnancies offspring. These concerns particularly heightened considering developmental origins disease (DOHaD) framework, which postulates that utero can programme lifelong The current review examines state knowledge this topic highlights avenues future investigation.

Language: Английский

Citations

38
How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health DOI Creative Commons

Ayazhan Akhatova,

Céline Jones,

Kevin Coward

et al.

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 16, 2025

Recent studies support the influence of paternal lifestyle and diet before conception on health offspring via epigenetic inheritance through sperm DNA methylation, histone modification, small non-coding RNA (sncRNA) expression regulation. Smoking may induce hypermethylation in genes related to anti-oxidation insulin resistance. Paternal obesity are associated with greater risks metabolic dysfunction alterations sperm. Metabolic changes, such as high blood glucose levels increased body weight, commonly observed fathers subjected chronic stress, addition an enhanced risk depressive-like behaviour sensitivity stress both F0 F1 generations. methylation is correlated quality ability fertilise oocytes, possibly a differentially regulated MAKP81IP3 signalling pathway. exposure toxic endocrine-disrupting chemicals (EDCs) also linked transgenerational transmission predisposition disease, infertility, testicular disorders, obesity, polycystic ovarian syndrome (PCOS) females changes during gametogenesis. As success assisted reproductive technology (ART) affected by diet, BMI, alcohol consumption, its outcomes could be improved modifying factors that dependent male choices environmental factors. This review discusses importance signatures sperm—including retention, sncRNA—for functionality, early embryo development, health. We discuss mechanisms which (obesity, smoking, EDCs, stress) impact epigenome.

Language: Английский

Citations

3
Impact of Endocrine Disruptors upon Non-Genetic Inheritance DOI Open Access
Debbie Montjean, Anne-Sophie Neyroud, Marina Yéfimova

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(6), P. 3350 - 3350

Published: March 20, 2022

Similar to environmental factors, EDCs (endocrine-disrupting chemicals) can influence gene expression without modifying the DNA sequence. It is commonly accepted that transgenerational inheritance of parentally acquired traits conveyed by epigenetic alterations also known as "epimutations". methylation, acetylation, histone modification, RNA-mediated effects and extracellular vesicle are mechanisms have been described so far be responsible for these epimutations. They may lead diverse phenotypes in progeny when they occur germ cells an affected individual. While EDC-induced health dramatically increased over past decade, limited on sperm epigenetics described. However, there has a gain interest this issue recent years. The gametes (sperm oocyte) represent targets thus route environmentally induced changes several generations. This review aims at providing overview might implicated inheritance.

Language: Английский

Citations

39
Mixtures of per- and polyfluoroalkyl substances (PFAS) alter sperm methylation and long-term reprogramming of offspring liver and fat transcriptome DOI Creative Commons

DruAnne L. Maxwell,

Oladele Oluwayiose, Emily Houle

et al.

Environment International, Journal Year: 2024, Volume and Issue: 186, P. 108577 - 108577

Published: March 16, 2024

Male fertility has been declining worldwide especially in countries with high levels of endocrine disrupting chemicals (EDCs). Per- and polyfluorinated alkyl Substances (PFAS) have classified as EDCs linked to adverse male reproductive health. The mechanisms these associations their implications on offspring health remain unknown. aims the current study were assess effect PFAS mixtures sperm methylome transcriptional changes metabolic tissues (i.e., liver fat). C57BL/6 mice exposed a mixture (PFOS, PFOA, PFNA, PFHxS, Genx; 20 µg/L each) for 18-weeks or water control. Genome-wide methylation was assessed F0 epidydimal using reduced representation bisulfite sequencing (RRBS) Illumina mouse array, while gene expression by bulk RNA 8-week-old derived from unexposed females. resulted 2,861 83 (Illumina) DMRs (q < 0.05). Functional enrichment revealed that PFAS-induced associated behavior developmental pathways RRBS, related lipid metabolism cell signaling. Additionally, 40 53 differentially expressed genes (DEGs) fat males, 9 31 DEGs females, respectively. alterations cholesterol mitotic cycle regulation myeloid leukocyte migration offspring, female erythrocyte development carbohydrate catabolism affected fat. Our results demonstrate exposure legacy newly emerging adult result aberrant altered sex-specific manner. These data indicate preconception males can be transmitted affect phenotype next generation.

Language: Английский

Citations

14
The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome—a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men DOI Creative Commons
Ariane Lismer, Xiaojian Shao, Marie-Charlotte Dumargne

et al.

Environmental Health Perspectives, Journal Year: 2024, Volume and Issue: 132(1)

Published: Jan. 1, 2024

The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT applied, well the Arctic, endocrine disrupting metabolite, p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) accumulates marine mammals and fish. p,p′-DDE exposures are linked birth defects, infertility, cancer, neurodevelopmental delays. Of particular concern potential of use impact generations come via heritable sperm epigenome.

Language: Английский

Citations

11
Lifestyle interventions to reduce endocrine-disrupting phthalate and phenol exposures among reproductive age men and women: A review and future steps DOI Creative Commons
Leah J. Martin, Yu Zhang, Olivia First

et al.

Environment International, Journal Year: 2022, Volume and Issue: 170, P. 107576 - 107576

Published: Oct. 14, 2022

Non-persistent endocrine-disrupting chemicals (EDCs), including phthalates and phenols, are ubiquitous in both the environment human body. A growing body of epidemiologic studies have identified concerning links between EDCs adverse reproductive developmental health effects. Despite consistent evidence, risk assessments policy interventions often arrive late. This presents an urgent need to identify evidence-based for implementation at clinical community levels reduce EDC exposure, especially susceptible populations. The life cycle (menarche menopause females after pubertal onset males) includes some most vulnerable periods environmental exposures, such as preconception perinatal stages, representing a key window opportunity intervene prevent unfavorable outcomes. review aims synthesize assess behavioral, dietary, residential EDC-driven develop recommendations subsequent, larger-scale that address knowledge-gaps current during cycle. We selected 21 primary evaluation, addition four supplemental interventions. Among these, accessible (web-based) educational resources, targeted replacement (known) toxic products, personalization intervention through meetings support groups, were promising strategies reducing concentrations. However, we document paucity phthalate phenol exposures years, among men. Accordingly, recommend additional, larger community-based exposure. Specifically, future should focus on short-term, mid-, long-term exposure reduction phenols. latter, especially, is required development public guidelines promote globally.

Language: Английский

Citations

36
Di-2-ethylhexyl phthalate (DEHP) exposure induces sperm quality and functional defects in mice DOI
Xuexia Liu, YaNan Liu,

Teng Zi

et al.

Chemosphere, Journal Year: 2022, Volume and Issue: 312, P. 137216 - 137216

Published: Nov. 9, 2022

Language: Английский

Citations

32
Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation DOI Creative Commons
Saira Amir, Olatunbosun Arowolo, Ekaterina Mironova

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 3, 2024

Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at time of conception. Sperm epigenome undergoes age-dependent changes increasing risks adverse conditions offspring conceived by fathers advanced age. The mechanism(s) linking paternal with epigenetic sperm remain unknown. is shaped compartment protected blood-testes barrier (BTB) known deteriorate Permeability BTB regulated balance two mTOR complexes Sertoli cells where complex 1 (mTORC1) promotes opening and 2 (mTORC2) its integrity. We hypothesized that this also responsible for epigenome. To test hypothesis, we analyzed reproductive outcomes, including DNA methylation transgenic mice cell-specific suppression mTORC1 ( Rptor KO) or mTORC2 Rictor KO). accelerated aging methylome resulted phenotype concordant older age, decreased testes weight counts, increased percent morphologically abnormal spermatozoa mitochondrial copy number. Suppression shift opposite associated physiological – rejuvenation mild parameters. These results demonstrate first regulates rate aging. Thus, pathway may be used as novel target therapeutic interventions rejuvenate advanced-age fathers.

Language: Английский

Citations

6