Maternal Vitamin C Intake during Pregnancy Influences Long-Term Offspring Growth with Timing- and Sex-Specific Effects in Guinea Pigs

Abstract

Our previous work in guinea pigs revealed that low vitamin C intake during preconception and pregnancy adversely affects fertility, pregnancy outcomes, and foetal and neonatal growth in a sex-dependent manner. To investigate the long-term impact on offspring, we monitored their growth from birth to adolescence (four months), recorded organ weights at childhood equivalence (28 days) and adolescence, and assessed physiological parameters like oral glucose tolerance and basal cortisol concentrations. We also investigated the effects of the timing of maternal vitamin C restriction (early vs. late gestation) on pregnancy outcomes and the health consequences for offspring. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum during preconception. Pregnant dams were then randomised into four feeding regimens: consistently optimal, consistently low, low during early pregnancy, or low during late pregnancy. We found that low maternal vitamin C intake during early pregnancy accelerated foetal and neonatal growth in female offspring and altered glucose homeostasis in the offspring of both sexes at an age equivalent to early childhood. Conversely, low maternal vitamin C intake during late pregnancy resulted in foetal growth restriction and reduced weight gain in male offspring throughout their lifespan. We conclude that altered vitamin C during development has long-lasting, sex-specific consequences for offspring and that the timing of vitamin C depletion is also critical, with low levels during early development being associated with the development of a metabolic syndrome-related phenotype, while later deprivation appears to be linked to a growth-faltering phenotype.

Keywords: ascorbic acid); foetal growth; foetal programming; guinea pig; maternal diet; metabolic function; postnatal growth; pregnancy; vitamin C (ascorbate.

Figure 1

Pregnancy weight gain. The graph represents average weight gain during pregnancy (mating to week of delivery) ± SD. Insert figure includes total dams and main figure includes dams carrying three pups. Optimal dams (orange, n = 30 insert, n = 11 main), low dams (purple, n = 32 insert, n = 10 main), low-optimal dams (green, n = 22 insert, n = 6 main), optimal-low dams (pink, n = 21 insert, n = 9 main). Data were analysed using repeated measures mixed-effects two-way ANOVA.

Figure 2

Postpartum salivary cortisol concentrations in dams. Optimal (orange, n = 10), low (purple, n = 10), low-optimal (green, n = 7), and optimal-low (pink, n = 7). Data are presented as group means ± SD and were analysed using one-way ANOVA.

Figure 3

Fractional weight gain in male (a) and female (b) offspring during the neonatal period. Optimal offspring (orange, n = 21 males, n = 20 females), low offspring (purple, n = 17 males, n = 17 females), low-optimal offspring (green, n = 17 males, n = 16 females), optimal-low offspring (pink, n = 18 males, n = 20 females). Data are presented as group means ± SD and were analysed using repeated measures mixed-effects two-way ANOVA.

Figure 4

Weight growth rate in male (a) and female (b) offspring from birth to four months. Data are pooled from pups randomised at birth to the juvenile (up to week four) and adolescent groups. Optimal offspring (orange, n = 21 males, n = 20 females), low offspring (purple, n = 17 males, n = 17 females), low-optimal offspring (green, n = 17 males, n = 16 females), optimal-low offspring (pink, n = 18 males, n = 20 females). Data are presented as group means ± SD and were analysed using repeated measures mixed-effects two-way ANOVA.

Figure 5

Glucose response in male (a) and female (b) offspring at weaning on day 21. Optimal offspring (orange, n = 8 males, n = 8 females), low offspring (purple, n = 6 males, n = 8 females), low-optimal offspring (green, n = 6 males, n = 5 females), and optimal-low offspring (pink, n = 5 males, n = 9 females). Data are presented as group means ± SD and were analysed within sex using one-way ANOVA.

Figure 6

Salivary cortisol concentrations in offspring on day zero (a), seven (b), and twenty-five (c). On day zero, optimal offspring (orange, n = 20 per sex), low offspring (purple, n = 20 per sex), low-optimal offspring (green, n = 8 per sex), and optimal-low offspring (pink, n = 8 per sex). On day seven, optimal offspring (orange, n = 12 per sex), low offspring (purple, n = 12 per sex), low-optimal offspring (green, n = 10 per sex), and optimal-low offspring (pink, n = 8 per sex). On day 25, optimal offspring (orange, n = 14 per sex), low offspring (purple, n = 14 per sex), low-optimal offspring (green, n = 10 per sex), and optimal-low offspring (pink, n = 10 per sex). Data are presented as group means ± SD and were analysed within sex using one-way ANOVA.