Placental morphofunctional adaptations and offspring outcomes after protein restriction before and during pregnancy in mice.

Proper fetal development depends on maternal nutrition. We investigated the placental morphofunctional adaptations to a low-protein diet, and their impact on fetal and newborn outcomes. Swiss mice were fed either normal (NPD, 20% crude protein, n=29) or low protein (LPD, 8% crude protein, n=26) diets two weeks before and throughout pregnancy. Dams were euthanized at gestational days (GD) 7.5 and 17.5 for morphological and molecular evaluations. No biometrical or histological alterations were observed in embryonic sites in both GDs. However, LPD placentae exhibited 14.2% increase in maternal sinusoid and 8% reduction in fetal vessel proportions (P<.05), without significant changes in cellular proliferation, or apoptosis. Placental gene expression analysis varied according to uterine location: LPD placentae near the ovary exhibited downregulation of Fatp4, Mtor, and Kiss1, while Stat3 was upregulated (P<.05); in the middle third of the uterine horn, Snat1 and Kiss1 were upregulated, while Snat4 was downregulated (P<.05); and close to the uterine body, Igf2r was downregulated, whereas Snat1 and Kiss1r were upregulated (P<.05), suggesting region-specific compensatory mechanisms. LPD placentae and fetuses were lighter and exhibited higher brain-to-liver weight ratio in both genders (P<.05). Maternal LPD intake disproportionately affected male fetuses, which presented higher placental efficiency (P<.05), yet failed to reach their full growth potential. At birth, although newborn size was not affected by LPD, liver weights were lower and brain-to-liver weight ratios remained higher (P<.05), particularly in males. Maternal LPD induces region-specific placental adaptations that partially compensate for nutrient restriction, yet still impair fetal growth, particularly in male offspring.