Undernutrition in ovine sex-discordant twin pregnancies selectively suppresses the fetal IGF–insulin–mTOR growth axis in the male lambs: Modulation by antioxidant and nutritional supplementation

In sheep, chronic undernutrition during twin gestation abolishes birth weight sexual dimorphism, being partially restored by antioxidants supplementation. The aim was to evaluate differences in the maternal-fetal endocrine environment and its influence on the differential growth of female and male fetuses in ovine twin pregnancies with discordant-sex conceptuses maintained under natural undernutrition, and to assess the effect of antioxidant supplementation and concentrated feed. Three groups of ewes ( n = 10 each) were compared: the control group (C) was maintained exclusively on natural pasture (~70% of energy and 30% of protein requirements). From day 62 to term, treated groups received antioxidants (AOx) or concentrate (NS). At 117 and 142 days of gestation (dGA), maternal plasma samples were collected to measure estradiol, progesterone, and cortisol, while umbilical cord plasma samples were obtained to measure insulin, IGF-1, IGF-2, and fetal cortisol. Lambs were delivered by cesarean section at 142 dGA, body weight was recorded, and a fetal skeletal muscle sample was collected for mTOR analysis by Western blot. Treatments did not affect maternal hormones. At 117 dGA, AOx and NS supplementation increased fetal plasma concentrations of IGF-1 and IGF-2; conversely, male fetuses of the Control group had lower IGF-1 and higher cortisol concentrations than their female co-twins. At 142 dGA, male fetuses showed higher concentrations of insulin and IGF-1, which were consistent with the expression of activated mTOR in muscle. It is concluded that maternal undernutrition imposes a greater burden on male fetuses, suppressing the growth axis; antioxidants partly reverse this, whereas maternal concentrate supplementation largely restores it.