Publications by authors named "Kevin D. Sinclair"

The developmental integrity and wellbeing of offspring are influenced by events that occur in utero, particularly around the time of conception. While extraneous factors such as environmental temperature and exposure to environmental chemicals can each have a bearing on these events, the epigenetic mechanisms that direct cellular differentiation during early development in ruminants are best described for studies which have investigated the effects of parental nutrition or pregnancy outcomes following assisted reproduction. In this article the case is made that the genetic constitution of an individual directs epigenetic responses to environmental stimuli, and consideration in this regard is also given to the origins of sexual dimorphism and mechanisms of germline intergenerational inheritance.

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Article Synopsis
  • The study focuses on how the intake of polyunsaturated fatty acids (PUFAs) during the periconceptional period affects embryonic development, particularly embryonic volume (EV) and head volume (HV) in pregnant women.* -
  • Findings reveal that many women have low omega-3 intake, and while higher PUFA intake is linked to a smaller HV/EV ratio, it does not correlate with individual EV or HV growth measures.* -
  • The research highlights a significant omega-3 deficiency in pregnant women and emphasizes the need for better awareness of PUFA intake to mitigate risks of negative pregnancy outcomes.*
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Introduction: Maternal lifestyle behaviors can affect blood pressure with consequences for maternal and offspring health. The aim of this study was to investigate the effectiveness of the Smarter Pregnancy digital lifestyle coaching program on maternal blood pressure during the first trimester.

Methods: The study was conducted on data of the Rotterdam Periconception Cohort from 2010 to 2019, and analysis was completed in 2024.

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  • Human reproductive and metabolic health has declined over the last 50 years due to exposure to a mix of environmental chemicals, leading to issues like poor sperm quality, early puberty, and increased obesity.
  • The impact of these chemicals is particularly strong during embryo and fetus development, with animal studies showing effects from both single chemicals and mixtures.
  • Future research should focus on the effects of complex chemical mixtures across multiple developmental stages to better understand genetic mechanisms and develop strategies for reducing these health risks.
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Environmental chemicals (ECs) have been associated with a broad range of disorders and diseases. Daily exposure to various ECs in the environment, or real-life exposure, has raised significant public health concerns. Utilizing the biosolids-treated pasture (BTP) sheep model, this study demonstrates that in-utero exposure to a real-life EC mixture disrupts hypothalamo-pituitary-gonadal (HPG) axis gene expression and reproductive traits in prepubertal (8-week-old, 8w) and adult (11-month-old) male sheep.

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Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R. A.

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Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A.

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Over recent decades, an extensive array of anthropogenic chemicals have entered the environment and have been implicated in the increased incidence of an array of diseases, including metabolic syndrome. The ubiquitous presence of these environmental chemicals (ECs) necessitates the use of real-life exposure models to the assess cumulative risk burden to metabolic health. Sheep that graze on biosolids-treated pastures are exposed to a real-life mixture of ECs such as phthalates, per- and polyfluoroalkyl substances, heavy metals, pharmaceuticals, pesticides, and metabolites thereof, and this EC exposure can result in metabolic disorders in their offspring.

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Background: maturation (IVM) of germinal vesicle intact oocytes prior to fertilization (IVF) is practiced widely in animals. In human assisted reproduction it is generally reserved for fertility preservation or where ovarian stimulation is contraindicated. Standard practice incorporates complex proteins (CP), in the form of serum and/or albumin, into IVM media to mimic the ovarian follicle environment.

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  • The study investigates how exposure to environmental chemicals in sheep during pregnancy affects growth and puberty in male and female offspring.
  • Male sheep exposed to these chemicals experienced lower body weight during adolescence but eventually caught up and surpassed control weights, while females showed no weight difference but experienced a delay in puberty.
  • The findings highlight that exposure to environmental chemicals leads to different growth and reproductive outcomes for males and females, suggesting potential implications for human health.
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  • Environmental chemical exposure may negatively affect male reproductive health, particularly through gestational exposure in sheep models.
  • Adult rams whose mothers were exposed to biosolids showed signs of testicular damage but had potential recovery indicators compared to earlier findings in younger sheep.
  • Increased levels of certain transcription factors in the testes suggest an adaptive response to environmental chemicals, indicating that the effects of these exposures can persist into adulthood and might impact fertility.
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  • The study focuses on in vitro production (IVP) of cattle embryos, emphasizing the need for oocyte maturation prior to fertilization and the effects of ovarian stimulation and progesterone (P4) support during oocyte retrieval (OPU).
  • Two experiments were conducted involving 10 Holstein heifers to assess the impact of P4 via corpus luteum presence or intravaginal devices (CIDR® and PRID®) on blastocyst yields across multiple OPU cycles.
  • Results showed that higher peripheral P4 levels were associated with the PRID® Delta device, and the interaction between CL presence and P4 device influenced blastocyst yield, particularly in cycles without a CL.
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  • Mothers who are obese before and after conception can face health problems, and their babies can also be affected.
  • Researchers looked at many studies to find specific markers that show how obesity impacts hormones, inflammation, and metabolism during the important time around conception.
  • They found interesting markers like leptin and insulin that could help predict health issues, but more research is needed to understand their importance better.
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Current declines in male reproductive health may, in part, be driven by anthropogenic environmental chemical (EC) exposure. Using a biosolids treated pasture (BTP) sheep model, this study examined the effects of gestational exposure to a translationally relevant EC mixture. Testes of 8-week-old ram lambs from mothers exposed to BTP during pregnancy contained fewer germ cells and had a greater proportion of Sertoli-cell-only seminiferous tubules.

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A healthy diet before and during pregnancy is beneficial in acquiring essential B vitamins involved in 1-carbon metabolism, and in maintaining a healthy gut microbiota. Each play important roles in fetal development, immune-system remodeling, and pregnancy-nutrient acquisition. Evidence shows that there is a reciprocal interaction between the one-carbon metabolism and the gut microbiota given that dietary intake of B vitamins has been shown to influence the composition of the gut microbiota, and certain gut bacteria also synthesize B vitamins.

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Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth.

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Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, 'real-life' exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage).

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The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders.

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Approximately one million in vitro produced (IVP) cattle embryos are transferred worldwide each year as a way to improve the rates of genetic gain. The most advanced programmes also apply genomic selection at the embryonic stage by SNP genotyping and the calculation of genomic estimated breeding values (GEBVs). However, a high proportion of cattle embryos fail to establish a pregnancy.

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One-carbon (1C) metabolism provides methyl groups for the synthesis and/or methylation of purines and pyrimidines, biogenic amines, proteins, and phospholipids. Our understanding of how 1C pathways operate, however, pertains mostly to the (rat) liver. Here we report that transcripts for all bar two genes (i.

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Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia and recurrent dieting, are also linked to PCOS. They can lead to the epigenetic dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis, thereby impacting on ovarian folliculogenesis.

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A method for the simultaneous quantification of B vitamins and related amines in one-carbon (1C) metabolism would benefit the study of diet and genetic/epigenetic regulation of mammalian development and health. We present a validated method for the simultaneous quantitative analysis of 13 B vitamers and four related 1C-pathway amine intermediates in liver using hydrophilic interaction chromatography (HILIC) coupled to electrospray ionization tandem mass spectrometry. Frozen sheep liver samples (50 mg) were homogenized in cold 50% acetonitrile containing 1% acetic acid with the addition of two isotope labelled internal standards.

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Article Synopsis
  • The use of genomic selection strategies in cattle breeding, especially through SNP interrogation, has enhanced genetic gains and is promising for in-vitro produced embryos by identifying desirable traits before pregnancy.
  • Karyomapping is a cutting-edge technique that allows for the detection of aneuploidy while also implementing genomic selection, potentially increasing pregnancy rates in cattle.
  • This study successfully demonstrates the effectiveness of Karyomapping, showing high accuracy in genetic and aneuploidy assessments, which could greatly benefit both cattle breeding and fundamental research on genetics.
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