Effect of maternal periconceptional undernutrition on male offspring physiology and testicular development

Epidemiological studies in humans, as well as animal models, have shown that maternal environment at critical periods of fetal development can condition offspring adult health. Previous studies have shown effects of maternal undernutrition during early to mid gestation on Sertoli cell proliferation and seminiferous tubule diameter in male lambs of 10 months of age. Delayed follicular maturation and meiosis in female fetuses have been reported after maternal undernutrition from mating. The aim of this project was to evaluate the long-term effects of maternal periconceptional undernutrition on offspring physiology and reproductive function. Postnatal development of male offspring is presented here. Fifty-two control females of Merinos d'Arles breed (R100) were fed a normal diet adapted to their needs, and 64 restricted females (R50) received 50% of their dietary needs from 15 days before until 30 days after synchronized breeding. Thereafter, both groups were fed to meet their nutritional requirements. Males were weighed at birth and every week. Blood samples were collected monthly to monitor plasma leptin and cortisol concentrations. Organ weights were recorded at commercial slaughter (35 kg) and histological analysis was performed on testicles and adrenals. Data were analysed by ANOVA or Student's test. Twenty-two live R100 and 34 live R50 male lambs were obtained. Gestation was significantly longer in the restricted group (P < 0.01). Growth rate, live weight, and age at slaughter were not significantly different between groups. Plasma leptin concentrations were significantly lower at birth (P < 0.001) and tended to be higher at 4 months of age (P = 0.09) in R50. There was a significant interaction between group, age, and litter size for basal cortisol concentrations: in singletons (n = 15 R50 and n = 8 R100), cortisol was significantly lower in R50 at 3 months of age (P < 0.05) and tended to be higher at 4 months whereas in twins (n = 17 R50 and n = 10 R100), cortisol was significantly lower at birth (P < 0.05) but not thereafter (triplets were not considered here because of low numbers). There was no statistical difference for carcass, testicle, or kidney weight. In contrast, carcass to live weight ratio and perirenal fat to live weight ratio were increased in all R50 (P < 0.05). Adrenal to live weight ratio tended to be increased in R50 lambs (P = 0.06). Histological examination revealed no statistical difference between groups for adrenal corticomedullary ratio, zona glomerulosa to medulla ratio, and zona fasciculata to medulla ratio. There was no significant difference for the analysis of testicular tissue (diameter and surface of seminiferous tubules). The expression of genes involved in testicular differentiation (SRY, 3β-HSD, OCT3/4, VASA, stra8, SOX9) is currently being studied by quantitative PCR and will be presented. These results confirm the effects of periconceptional undernutrition on metabolic function but so far, no effect has been demonstrated on testicular histology. Litter size seems to play an important role, because effects were different between singletons and twins