A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause.
BACKGROUND
The primary determinant of reproductive age in women is the number of ovarian non-growing (primordial, intermediate and primary) follicles (NGFs). To better characterize the decline in NGF number associated with aging, we have employed modern stereology techniques to determine NGF number in women from birth to menopause.


METHODS
Normal human ovaries were collected from 122 women (aged 0-51 years) undergoing elective oophorectomy, organ donation or autopsy. After gross pathologic examination, systematic random sampling was utilized to obtain tissue for analysis by the fractionator/optical disector method. Models to describe the resulting decay curve were constructed and evaluated.


RESULTS
NGF decay was best described by a simple power function: log (y) = ax(b) + c, where a, b and c are constants and y = NGF count at age x (R(2) = 0.84, Sums of Squares Error = 28.18 on 119 degrees of freedom). This model implies that follicles decay faster with increasing age.


CONCLUSIONS
Unlike previous models of ovarian follicle depletion, our model predicts no sudden change in decay rate, but rather a constantly increasing rate. The model not only agrees well with observed ages of menopause in women, but also is more biologically plausible than previous models. Although the model represents a significant improvement compared with earlier attempts, a considerable percentage of the variation in NGF number between women cannot be explained by age alone.
Hansen
Karl R
KR
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190, USA. karl-hansen@ouhsc.edu
Knowlton
Nicholas S
NS
Thyer
Angela C
AC
Charleston
Jay S
JS
Soules
Michael R
MR
Klein
Nancy A
NA
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008954:Models, Biological; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D012098:Reproduction / Q000502:physiology*