Lipids in health and disease.

Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.

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Environmental epigenetics: prospects for studying epigenetic mediation of exposure–response relationships

The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health

BACKGROUND

Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously.


METHODS

A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case–control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders.


RESULTS

A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case–control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: −0.46(−1.41, 0.49), PEG1-MEST: 0.47 (−2.07, 3.01), GRB10: −0.05 (−0.43, 0.33), IGF2: −0.15 (−1.09, 0.79), SNRPN: −0.55 (−1.55, 0.46), KvDMR/KCNQ10T1: −0.16 (−0.34, 0.02) and PEG3: −0.24 (−1.72, 1.24).


CONCLUSIONS

There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed.

A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously

Repeated implantation failure (RIF) is determined when embryos of good quality fail to implant following several in vitro fertilization (IVF) treatment cycles. Implantation failure is related to either maternal factors or embryonic causes. Maternal factors include uterine anatomic abnormalities, thrombophilia, non-receptive endometrium and immunological factors. Failure of implantation due to embryonic causes is associated with either genetic abnormalities or other factors intrinsic to the embryo that impair its ability to develop in utero, to hatch and to implant. New methods of time-lapse imaging of embryos and assessment of their metabolic functions may improve selection of embryos for transfer, and subsequent outcomes for IVF patients, as well as for those diagnosed with RIF. This review discusses the various causes associated with RIF and addresses appropriate treatments.

Assessment and treatment of repeated implantation failure (RIF)

Preimplantation genetic diagnosis (PGD) refers to a procedure for genetically analyzing embryos prior to implantation, improving the chance of conception for patients at high risk of transmitting specific inherited disorders. This method has been widely used for a large number of genetic disorders since the first successful application in the early 1990s. Polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) are the two main methods in PGD, but there are some inevitable shortcomings limiting the scope of genetic diagnosis. Fortunately, different whole genome amplification (WGA) techniques have been developed to overcome these problems. Sufficient DNA can be amplified and multiple tasks which need abundant DNA can be performed. Moreover, WGA products can be analyzed as a template for multi-loci and multi-gene during the subsequent DNA analysis. In this review, we will focus on the currently available WGA techniques and their applications, as well as the new technical trends from WGA products.

/pdf/whole-genome-amplification-in-preimplantation-genetic-vhoxks32pa.pdf

Whole genome amplification in preimplantation genetic diagnosis

Epidemiological studies have reported a higher incidence of growth disorders among newborns conceived by in vitro fertilization (IVF), suggesting that IVF may be disruptive to the process of embryonic and fetal growth. However, the long-term effects of IVF on the growth and molecular mechanisms remain unclear. Therefore, we evaluated the body weight of IVF mice from birth to the age of 1.5 yr. In addition, we analyzed gene expression of insulin-like growth factor 2 (Igf2), H19, Igf2 receptor (Igf2r), and miR-483 and their DNA methylation status using real-time quantitative PCR, Western blot, and pyrosequencing. The results showed that when compared with the in vivo group, the body weight of IVF mice was significantly higher at birth, but lower at 3 wk; in addition, gene expression of Igf2 was significantly up-regulated, with down-regulated expression of H19 and miR-483 in both liver and skeletal muscle. At the same time, there were significant differences in the DNA methylation rates of Igf2/H19 differentially methylated regions (DMRs) and the IGF2 protein expression between the two groups. In the IVF treatment group, the differences in growth and expression disappeared at 10 wk. However, at 1.5 yr of age, aberrant expressions of Igf2/H19, Igf2r, and miR-483 and changes in DNA methylation rates in the liver or skeletal muscle were again observed in IVF mice. Our results indicate that IVF causes alterations in mouse growth during the postnatal periods that may be associated with alterations in Igf2/H19 expression and likely involve the regulation of miR-483 and the methylation status of Igf2/H19 DMRs.

https://bioone.org/journals/biology-of-reproduction/volume-88/issue-3/biolreprod.112.106070/In-Vitro-Fertilization-Alters-Growth-and-Expression-of-Igf2-H19/10.1095/biolreprod.112.106070.pdf

In Vitro Fertilization Alters Growth and Expression of Igf2/H19 and Their Epigenetic Mechanisms in the Liver and Skeletal Muscle of Newborn and Elder Mice

https://www.fertstert.org/article/S0015-0282(11)00253-6/pdf

Evaluation of DNA methylation status at differentially methylated regions in IVF-conceived newborn twins.

Background
Lipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART). Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study.

/pdf/alteration-of-fatty-acid-metabolism-in-the-liver-adipose-1jqal5y8ux.pdf

Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice

Lei Li

Papers

Whole genome amplification in preimplantation genetic diagnosis

In Vitro Fertilization Alters Growth and Expression of Igf2/H19 and Their Epigenetic Mechanisms in the Liver and Skeletal Muscle of Newborn and Elder Mice

Evaluation of DNA methylation status at differentially methylated regions in IVF-conceived newborn twins.

Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice

Genome-wide DNA methylation patterns in IVF-conceived mice and their progeny: A putative model for ART-conceived humans