Disturbed calcium homeostasis has detrimental effects on brain development and function, particularly in early life because of epigenetic determination of early nutrition on later health. We hypothesized that the imbalance of calcium status in early life might have long-lasting effects on brain DHA accretion though epigenetic modification on fatty acid desaturases (Fads). Three to four week old C57BL/6J female mice were fed 3 reproductive diets with different calcium concentrations - low (LC, 0.25%), normal (NC, 0.70%) and high-calcium (HC, 1.20%) respectively throughout pregnancy and lactation. Maternal LC diet reduced tissue (brain and hepatic) DHA concentrations in both male and female offsprings at postnatal 21 day, with reductions in male instead of female offsprings in adulthood. Maternal HC diet only reduced hepatic DHA concentration in adult male offsprings. Furthermore, maternal LC diet reduced hepatic but increased brain expressions of Fads1 or Fads2 in 21-days old offsprings, with similar changes in adult male instead of female offsprings. Maternal HC diet reduced hepatic or brain expressions of Fads1 or Fads2 in 21-days old offsprings, and only reduced Fads2 in the liver with adult male offsprings. Determination of DNA methylation (CpG4, CpG5, CpG7,8, CpG14-17 and CpG19) showed that maternal LC diet caused hypermethylation of Fads2 promoter in the liver and hypomethylation in the brain in 21-days old offsprings, as well as in adult male offsprings. These data demonstrate that the imbalance of calcium intake in early life might have long-term gender-specific effects on brain accretion of DHA mediated by altered DNA methylation and associated expressions of Fads. (C) 2019 Published by Elsevier Inc.