A DNA methylation state transition model reveals the programmed epigenetic heterogeneity in human pre-implantation embryos.

Background: During mammalian early embryogenesis, expression and epigenetic heterogeneity emerge before the first cell fate determination, but the programs causing such determinate heterogeneity are largely unexplored.

Results: Here, we present MethylTransition, a novel DNA methylation state transition model, for characterizing methylation changes during one or a few cell cycles at single-cell resolution. MethylTransition involves the creation of a transition matrix comprising three parameters that represent the probabilities of DNA methylation-modifying activities in order to link the methylation states before and after a cell cycle.

Maternal obesity programs reduced leptin signaling in the pituitary and altered GH/IGF1 axis function leading to increased adiposity in adult sheep offspring.

Studies in rodents highlight a role for leptin in stimulation of pituitary growth hormone (GH) secretion, with an impact on body composition regulation. We have reported that maternal obesity (MO) during ovine pregnancy results in hyperphagia, glucose-insulin dysregulation, increased adiposity, hypercortisolemia and hyperleptinemia in mature offspring subjected to a bout of ad libitum feeding. We hypothesized that MO reduces leptin signaling in the pituitary and down regulates the GH/IGF1 axis and increases circulating cortisol leading to increased adiposity in their adult offspring.

Maternal obesity in sheep increases fatty acid synthesis, upregulates nutrient transporters, and increases adiposity in adult male offspring after a feeding challenge.

Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term.

Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels.

Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation (day 75) or late (day 135) gestation.

Maternal nutrient restriction in the ewe from early to midgestation programs reduced steroidogenic enzyme expression and tended to reduce progesterone content of corpora lutea, as well as circulating progesterone in nonpregnant aged female offspring.

Background: Previously we reported decreased circulating progesterone and fertility in one and two year old ewes born to undernourished mothers. This study was designed to investigate if this reduction in progesterone persisted into old age, and if it did, what mechanisms are involved.

Methods: Ewes were fed a nutrient restricted (NR, 50% of NRC recommendations) or control (C, 100% of NRC) diets from day 28 to 78 of gestation, then all were fed to requirements through parturition and weaning.

Maternal obesity: how big an impact does it have on offspring prenatally and during postnatal life?

Obesity is increasing at an epidemic rate in women of reproductive age. Not only does obesity during pregnancy lead to increased maternal health concerns, it is also linked to an increase in adiposity and components of the metabolic syndrome in the children and grandchildren of obese women. The potential transgenerational impact of maternal obesity on the health of future generations will undoubtedly result in increasing healthcare costs for society.

Early maternal undernutrition programs increased feed intake, altered glucose metabolism and insulin secretion, and liver function in aged female offspring.

Insulin resistance and obesity are components of the metabolic syndrome that includes development of cardiovascular disease and diabetes with advancing age. The thrifty phenotype hypothesis suggests that offspring of poorly nourished mothers are predisposed to the various components of the metabolic syndrome due to adaptations made during fetal development. We assessed the effects of maternal nutrient restriction in early gestation on feeding behavior, insulin and glucose dynamics, body composition, and liver function in aged female offspring of ewes fed either a nutrient-restricted [NR 50% National Research Council (NRC) recommendations] or control (C: 100% NRC) diet from 28 to 78 days of gestation, after which both groups were fed at 100% of NRC from day 79 to lambing and through lactation.