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Ultrastructure of the Resting Ovarian Follicle Pool in Healthy Young Women¹

^a Department of Obstetrics and Gynaecology, Diakonessenhuis Utrecht, 3582 KE Utrecht, The Netherlands ^b Department of Human Genetics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands ^c Department of Biochemistry, Cell Biology and Histology, University of Utrecht, 3584 CM Utrecht, The Netherlands ^d Department of Cell Biology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands ^e Department of Public Health, Faculty of Medicine, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands ^f Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands

In humans, follicle quantity and quality decline with age by atresia. In the present study we aimed to describe the quality of the follicle pool through an ultrastructural investigation of resting follicles in young healthy women. From ovarian biopsies of 7 women aged 25–32 yr, 182 small follicles were morphometrically assessed for various signs of atresia. Morphometric variables were analyzed by principal components analysis (PCA) to demonstrate correlations between variables and to construct an objective follicle score. One third of small follicles consisted of primordial follicles. Nucleus:cell ratios remained constant for oocytes and granulosa cells from primordial to primary follicles, suggesting that follicles up to primary stages belong to the resting pool. The distribution of follicle quality scores as derived from PCA showed that most follicles were of good quality and with little signs of atresia. Atresia in resting follicles appears to be a necrotic process, starting in the ooplasma. Early atresia was characterized by increasing numbers of multivesicular bodies and lipid droplets, dilation of smooth endoplasmic reticulum and Golgi, and irregular mitochondria with changed matrix density. In progressive atresia mitochondrial membranes ruptured, oocyte nuclear membranes were indented or ruptured, and the ooplasma showed extensive vacuolarization. The early involvement of mitochondria in this process suggests that damage is induced by oxygen radicals. PCA follicle quality scores can be reliably approximated using a reduced number of seven morphometric variables, which were selected by stepwise forward analysis. The algorithm to calculate these follicle scores is presented.

First decision: 5 February 2001.

¹ Financial support was received from Serono Benelux, Abbott.

² Correspondence: J.P. de Bruin, Department of Obstetrics and Gynaecology, Diakonessenhuis Utrecht, Bosboomstraat 1, 3582 KE Utrecht, The Netherlands. FAX: 31 30 2505433; jp{at}debruin-kers.demon.nl

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