Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats.

Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.

Solution NMR in human embryo culture media as an option for assessment of embryo implantation potential.

NMR offers the potential to holistically screen hundreds of metabolites and has already proved to be a powerful technique able to provide a global picture of metabolic changes in a wide range of biological systems underlying complex and multifactorial matrixes. This review covers the literature until May 2020 centered on the early prediction of the viability of in vitro developed embryos using several analytical techniques, including NMR. Nowadays, the predominant non-invasive technique for selecting viable embryos is based on morphology, where variables associated with the rate of cleavage and blastocyst formation are evaluated by the embryologist following standardized criteria that are somewhat subjective. This morphological approach is therefore inadequate for the prediction of embryo quality, and several studies have focused on developing new non-invasive methods using molecular approaches based particularly on metabolomics. This review outlines the potential of NMR as one of these non-invasive in vitro methods based on the analysis of spent embryo culture media.