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Dietary Depletion of Cow's Milk microRNAs Impairs Fecundity in Mice
Author(s) -
Sadri Mahrou,
Xie Fang,
Wood Jennifer,
Zempleni Janos
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.673.5
Subject(s) - fecundity , litter , biology , microrna , zoology , andrology , analysis of variance , endocrinology , medicine , physiology , genetics , gene , ecology , population , environmental health
Background Traditionally, microRNAs have been considered endogenous regulators of gene expression. Recently, we have made the paradigm‐shifting discovery that humans absorb cow's milk microRNAs (encapsulated in exosomes) by endocytosis, and that body pools of circulating microRNAs decrease by >60% in mice fed milk microRNA‐depleted diets. Hypothesis Dietary depletion of microRNAs impairs fecundity in mice, i.e., causes phenotypes of sub‐optimal health. Methods C57BL/6J mice were fed modified AIN‐93G diets depleted of microRNAs [denoted ExosomeMinus (E‐); <10% microRNAs compared with control diets, E+], starting at age 3 weeks through age 15 weeks. Mice were mated in all possible permutations (E+ males × E+ females, E+ × E−, E− × E +, E− × E−; n=8 pairs per group). Variables of fecundity were analyzed and statistical significance was assessed using one‐way ANOVA and Dunnett's post‐hoc test. Results Sixty‐two to 75% of mating did not result in pregnancy if at least one parent was fed the E− diet, compared with only one (12.5%) failed mating in controls. The average litter size produced by E+/E+ breeders was twice the size in other groups: 7.6±1.9 pups for E+ males/E+ females, 3.6±3.2 for E+/E−, 3.5±3.0 for E−/E+, and 4.1±3.4 for E−/E−; P <0.05, n=8). The average birth weight of pups born to dams fed the E− diet (E+ males) was 1.13±0.11 g compared to 1.30±0.09 g in E+/E+ breeders ( P <0.05). MicroRNA depletion also impaired survival of litters to weaning (3 weeks) if dams were continued on the previous diets: 100% survival in E+/E+, zero survival in E+/E− and E−/E+, and one surviving litter in E−/E−. The hepatic concentrations of purine metabolites were 65% higher in E‐females compared to E+ females (16.6±3.3 vs. 10.1±1.0 μmol/L xanthine; P <0.05, n=5), suggesting a potential mechanism leading to low fecundity. Conclusions Depletion of dietary microRNAs elicits disease phenotypes. Support or Funding Information Supported by NIFA/USDA 2015‐67017‐23181, NIH 1P20GM104320, Gerber Foundation, Egg Nutrition Center, USDA W‐3002 and Hatch