Variation in ovarian follicle density during human fetal development

To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 mu m(2)) of the ovarian cortex and the number of follicles per mmA(3) was calculated. The number of follicles per 0.25 mmA(2) ranged from 10.9 (+/- 4.8) in a neonate to 34.7 (+/- 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 +/- 6.2) and highest at 26 weeks (32 +/- 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.