Developmental programming: does prenatal steroid excess disrupt the ovarian VEGF system?

ORTEGA HH; VEIGA-LOPEZ A; SREEDHARAN S; VELAZQUEZ M; SALVETTI NR; PADMANABHAN, V

BIOLOGY OF REPRODUCTION

SOC STUDY REPRODUCTION

Lugar: Madison; Año: 2015 vol. 93 p. 1 - 11

0006-3363

Prenatal testosterone (T), but not dihydrotestosterone (DHT),excess disrupts ovarian cyclicity and increases follicular recruitmentand persistence. We hypothesized that the disruption inthe vascular endothelial growth factor (VEGF) system contributesto the enhancement of follicular recruitment and persistencein prenatal T-treated sheep. The impact of T/DHTtreatments from Days 30 to 90 of gestation on VEGFA, VEGFB,and their receptor (VEGFR-1 [FLT1], VEGFR-2 [KDR], andVEGFR-3 [FLT4]) protein expression was examined by immunohistochemistryon Fetal Days 90 and 140, 22 wk, 10 mo(postpubertal), and 21 mo (adult) of age. Arterial morphometrywas performed in Fetal Day 140 and postpubertal ovaries.VEGFA and VEGFB expression were found in granulosa cells atall stages of follicular development with increased expression inantral follicles. VEGFA was present in theca interna, whileVEGFB was present in theca interna/externa and stromal cells.All three receptors were expressed in the granulosa, theca, andstromal cells during all stages of follicular development. VEGFR-3 increased with follicular differentiation with the highest levelseen in the granulosa cells of antral follicles. None of themembers of the VEGF family or their receptor expression werealtered by age or prenatal T/DHT treatments. At Fetal Day 140,area, wall thickness, and wall area of arteries from the ovarianhilum were larger in prenatal T- and DHT-treated females,suggestive of early androgenic programming of arterial differentiation.This may facilitate increased delivery of endocrinefactors and thus indirectly contribute to the development of themultifollicular phenotype.ovary, PCOS, sheep, testosterone,