Size at birth and adult fat mass in twin sheep are determined in early gestation

- Reduced size at birth and shorter gestation length are both associated with increased risks of non‐communicable diseases (NCD) in later adult life. - Twins are born both smaller and earlier than singletons and adult twins also are reported to be at increased risk of common NCDs such as diabetes. - The smaller size and shorter gestation length of twins has been presumed to be due to a lack of intrauterine space and/or limitations of placental nutrient supply in late gestation, but there are few data to support this. - We show that size at birth and adult fat mass in twin sheep are determined largely in early gestation. - Knowledge of the mechanisms underlying early pregnancy determination of fetal growth and gestation length in twins are likely to increase understanding of how early pregnancy factors influence lifelong health for offspring from all pregnancies

Twin conception in sheep leads to impaired insulin sensitivity and sexually dimorphic adipose tissue and skeletal muscle phenotypes in adulthood

Twins are often born small and early and have increased risk of obesity and diabetes later in life. Twin conception in sheep, regardless of whether the pregnancy continues as twins or is reduced to singleton in early gestation, alters offspring growth trajectory and body composition in young adulthood. We hypothesized that twin conception would result in insulin resistance in adulthood, with insulin-resistant adipose tissue and skeletal muscle phenotypes. At 3 years of age, body weight was not different among singletons, twins, and reductions; females weighed less than males. Singletons were leaner than reductions, with twins intermediate. Twins and reductions had decreased insulin sensitivity compared with singletons (singletons: mean [standard error of the mean]: 4.75 [0.4], twins: 3.34 [0.3], reductions: 3.67 [0.2] mg·I μU-'1·kg-'1·min-'1, P <.01). There were no group differences in adipocyte size, adipose tissue, or circulating tumor necrosis factor α, monocyte chemoattractant protein 1, or interleukin 6 concentrations. In males, omental and subcutaneous adipose SLC2A4 was 1.5- to 2.0-fold greater in twins and reductions than in singletons (P <.01) and SLC2A1 was greater in reductions than in singletons. Skeletal muscle IRS-1 was decreased in male twins but increased in female twins, compared to singletons (P ≤.01), with no effect on reductions in either sex. Skeletal muscle SLC2A4 was decreased in female twins and reductions but elevated in male twins and reductions compared to singletons (P ≤.01). We conclude that adult twin insulin resistance is not due to adipose tissue phenotype, but potentially phenotypic effects in skeletal muscle, and obesity is a result of twin conception per se with its origins in early gestation

Do Alterations in placental 11β-hydroxysteroid dehydrogenase (11βHSD) activities explain differences in fetal hypothalamic-pituitary- adrenal (HPA) function following periconceptional undernutrition or twinning in sheep?

Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11β-hydroxysteroid dehydrogenase (11βHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11βHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11βHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P <.05) and was higher in twins than in singletons (P <.05). Furthermore, placental 11βHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P =.01). At day 85, fetal plasma cortisol (P <.001) and cortisone (P <.001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P =.01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11βHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life