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

Objective: To 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. Design: Experimental study. Setting: University-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. (Fertil Steril (R) 2010; 93: 2572-80. (C) 2010 by American Society for Reproductive Medicine.)