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Age-Related Changes in the Ultrastructure of the Resting Follicle Pool in Human Ovaries¹

Department of Obstetrics & Gynaecology,³ Diakonessenhuis Utrecht, 3582 KE Utrecht, The Netherlands Department of Human Genetics,⁴ University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands Department of Biochemistry,⁵ Cell Biology and Histology, University of Utrecht, 3584 CM Utrecht, The Netherlands Department of Cell Biology,⁶ University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands Department of Public Health,⁷ Faculty of Medicine, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands Department of Reproductive Medicine,⁸ Division of Perinatology and Gynaecology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands

Age-related decline of fertility in women is the result of the decline in both quantity and quality of the resting ovarian follicle pool. The aim of the present study was to determine whether the decline of follicle quality with age is reflected by ultrastructural changes in the resting follicle pool. Ovarian biopsy specimens were obtained by laparoscopy from seven healthy women aged 25–32 yr (young group) and from 11 healthy women aged 38–45 yr (advanced-age group). A total of 182 resting follicles from the young group were compared with 81 resting follicles from the advanced-age group for signs of age-related changes by transmission-electron microscopy. The ooplasmic fraction of vacuoles was increased (P = 0.02), and the fraction of mitochondria decreased (P = 0.005), in the advanced-age group. Also, the density of the mitochondrial matrix (P < 0.001) and the frequency of dilated smooth endoplasmic reticulum (SER; P = 0.001) and Golgi complex (P = 0.02) were increased with age. The frequencies of ruptured mitochondrial membranes (P = 0.001) and dilated SER (P = 0.003) were increased with age in the granulosa cells. Overall follicle-quality scores, which should reflect atretic changes, were not different for the young and advanced-age groups. In conclusion, in resting follicles, the morphological changes with age are different from the changes seen in quality decline by atresia. The morphological changes with age specifically involved the mitochondria, the SER, and the Golgi complex, and they may be the cause of atresia on initiation of follicular growth because of the substantial increase in metabolic requirements.

¹ Supported by Serono Benelux, Abbott (unrestricted grants).

² Correspondence: J.P. de Bruin, Department of Reproductive Medicine, Division of Perinatology and Gynaecology, University Medical Centre, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. FAX: 30 2505433; jp{at}debruin-kers.demon.nl

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