According to the fetal origins hypothesis, normal growth and development of abdominal organs is disturbed by intra-uterine growth restriction, leading to diseases later in life. The aims of this study were to investigate the effect of growth restriction on the ovaries of human fetuses and to investigate the dynamics of follicular growth in normal fetuses. We selected 21 normal female fetuses (controls) and seven severely intra-uterine growth-restricted female fetuses (IUGR cases) from all autopsy records over a 10-year period. Ovarian volume was calculated and from histological sections the volume-percentage of follicles in the ovarian cortex, the maximum diameters of individual follicles and the distribution of the follicle classes and oogonia were determined. The volume of the ovaries increased significantly from 0.10 to 0.36 cm3 in the second half of gestation. The mean volume-percentage of ovarian follicles and the mean follicle diameter significantly increased with 0.48% and 0.52 μm per week, respectively. Class B/C (intermediary) follicles (72%) were predominantly present. Class B (primordial) follicles decreased from over 20% to less than 10% and class C (primary) increased from 6 to 19%. Class A (oogonia) were frequently present before 30 gestational weeks, but were rare after that age. For all studied parameters we did not find differences between IUGR cases and controls. Intra-uterine growth restriction does not seem to disturb ovarian development in the human fetus. In the second half of gestation the follicle pool increases by the growth of individual follicles, the transition of follicle to larger classes, and probably by increasing follicle numbers. As most follicles at term were class B/C and C, follicles up to class C are probably part of the resting stock. Copyright

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Early Human Development
Department of Immunology

de Bruin, J.P, Nikkels, P.G.J, Bruinse, H.W, van Haaften, M, Looman, C.W.N, & te Velde, E.R. (2001). Morphometry of human ovaries in normal and growth-restricted fetuses. Early Human Development, 60(3), 179–192. doi:10.1016/S0378-3782(00)00118-3