Metabolic programming of ovarian angiogenesis and folliculogenesis by maternal malnutrition during lactation

ObjectiveTo evaluate whether maternal malnutrition during lactation programs ovarian folliculogenesis and the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and its receptors KDR, Flt-1, and FGFR.DesignExperimental study.SettingUniversity-based research laboratory.Animal(s)Adult female rats from a urogenital research laboratory.Intervention(s)Six rat dams randomly assigned to the following groups: control group (C), with free access to a standard laboratory diet containing 23% protein; and a protein-energy-restricted group (PER), with free access to an isoenergy and protein-restricted diet containing 8% protein. After weaning, the female pups had free access to the standard laboratory diet until 90 days of age, when they were sacrificed at the proestrum stage.Main Outcome Measure(s)Quantification of ovarian follicles, vessels, and expression of growth factors and their receptors.Result(s)Maternal malnutrition during lactation caused a significant reduction in the number of primordial (C = 6.60 ± 0.24, PER = 5.20 ± 0.20), primary (C = 5.80 ± 0.66, PER = 4.00 ± 0.31), and Graafian follicles/section (C = 2.18 ± 0.29, PER = 1.08 ± 0.37), in KDR (C = 0.22 ± 0.04, PER = 0.09 ± 0.01), Flt-1 (C = 0.28 ± 0.05, PER = 0.12 ± 0.02), and FGFR mRNA expression (C = 0.34 ± 0.05, PER = 0.13 ± 0.05) and in the vessel density of follicles (C = 17.26 ± 2.30, PER = 9.96 ± 0.97).Conclusion(s)Maternal malnutrition during lactation programs the follicular development by a reduction of VEGF and FGF mRNA receptors expression, probably from a direct action on the follicular development or a reduction in vasculature resulting in a decreased delivery of folliculotrophic substances in PER animals.