Males of low birth weight have programmed adult bone deficits. Disease development due to low birth weight is not limited to the first directly exposed generation (F1) but has the potential to transmit to subsequent generations. We examined bone health from postnatal life to late adulthood in F2 male rats born to normal birth weight or growth restricted mothers (F1) and assessed the effects of maternal stress during pregnancy.
During late gestation in the female rat, uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery in the F0 generation. F1 females were mated and randomly allocated to an Unstressed or Stressed (24 h metabolic cage, tail-cuff blood pressure, glucose tolerance test) pregnancy groups.
F2 offspring born to mothers who experienced stress during their pregnancy were lighter at birth (4-6%). Compared to F2 Control Unstressed males, low maternal birth weight (Restricted Unstressed) as well as maternal stress in pregnancy (Control and Restricted Stressed) led to the development of deficits at day 35 in cortical content (-15-18%), cortical density (-4-6%) and Y-axis stress strain index (-22-25%) in males. At 6 months of age, these deficits in content and density were ameliorated. Maternal stress, regardless of maternal birth weight, programmed decreased trabecular density (-6%) at 6 months, while periosteal circumference and Y-axis stress strain index were increased (3-7%) in Restricted male offspring independent of maternal stress. No deficits were apparent at 12 months. Maternal stress, independent of maternal birth weight, programmed deficits in endosteal and periosteal circumferences (-5-13%) and decreased X-axis stress strain index (-5%) at 16 months.
Maternal low birth weight, programs postnatal bone deficits in the next generation. Stress during pregnancy, programmed males to develop adult bone deficits, independent of maternal birth weight.