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Serum Anti-Müllerian Hormone Levels Reflect the Size of the Primordial Follicle Pool in Mice

Department of Internal Medicine (M.E.K., P.K., B.M.N.v.d.L.-B., F.H.d.J., A.P.N.T., J.A.V.), Erasmus MC, 3000 DR Rotterdam, The Netherlands; and School of Biological and Molecular Sciences (M.F.M., N.P.G.), Oxford Brookes University, Headington, Oxford OX3 0BP, United Kingdom

Address all correspondence and requests for reprints to: Jenny A. Visser, Ph.D., Department of Internal Medicine, Room Ee532, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: j.visser{at}erasmusmc.nl.

Reproductive aging is the decline of female fertility with age. It is caused by the decrease in the number of growing follicles, resulting from primordial follicle pool depletion. Recently, we have shown that anti-Müllerian hormone (AMH) is produced by growing follicles, and studies in women indicate that serum AMH levels decrease with age and correlate with antral follicle count. However, whether serum AMH levels correlate directly with the size of the primordial follicle pool cannot be determined in women. In this work, we describe studies in mice in which we determined the dynamics of ovarian follicles during aging. Furthermore, we describe the development of a mouse AMH ELISA, allowing us to measure AMH levels in mice, for the first time. We observed that serum AMH levels decline with increasing age, whereas expression of AMH in individual growing follicles, studied by immunohistochemistry, did not change with age. Thus, the decline in serum AMH correlates directly with the decline in the number of growing follicles (r = 0.86, P < 0.0001). We observed that the number of growing follicles correlated with the number of primordial follicles (r = 0.93, P < 0.0001). Similarly, we found a strong correlation between AMH levels and number of primordial follicles (r = 0.83, P < 0.0001). In conclusion, serum AMH levels reflect the size of the primordial follicle pool in aging mice. Therefore, AMH is an excellent marker to assess the quantitative aspect of ovarian reserve, which may be useful for women at risk for early ovarian aging such as survivors of childhood cancers.

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