Position of follicles in normal human ovary during definitive histogenesis

Background: Follicular growth in the mammalian ovary follows a geographically determined pattern, but no exhaustive data about their spatial localization in the cortex of human ovary exists. Aim: The aim of this study is to assess the spatial position of the follicles during human ovarian definitive histogenesis using morphometric methods. Subjects: Ovaries removed from four fetuses, five newborns and one 8-month-old child with 46,XX karyotype was used. Outcome measures: The position of the different follicle categories (primordial, primary, secondary and antral) was estimated as percentage distance of the centroid of the follicle from the cortico-medullary boundary. Results: In normal ovaries, during definitive histogenesis, the primordial follicles progressively occupy more peripheral parts of the cortex (on average, 41% of cortical length at 20 weeks of fetal development, 53% at birth, 68% at 8 postnatal months). Primary follicles were crowded in the inner part of the cortex (newborn: 30-40% of cortical length; 8 months: 52% of cortical length). Secondary and antral follicles were sampled in all neonatal specimens and in the 8-month old specimen; they were grouped next to the cortico-medullary boundary. Conclusions: Ovarian development corresponded to a migration of the maximum crowding of follicles from a position next to the medulla towards a more peripheral location. The control of the primordial follicle assembly, recruitment and development are coordinated by locally produced paracrine factors. The action of these factors seems to follow a negative gradient from the cortex toward the medulla.