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

Abstract

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.

The association between the oocyte pool and aneuploidy: a comparative study of the reproductive potential of young and aged mice

“…Other researchers have used the fractionator/optical disector technique to estimate the human numbers of primordial follicles (oocyte pools) and determined that the age-adjusted correlation between serum AMH and the oocyte pool is 0.48, which supports the view that AMH reflects the size of the oocyte pool [14]. It has been reported that in 4-to 18-month-old C57BL/6j mice, the serum AMH levels decline with increasing age and directly correlate with declining numbers of growing and primordial follicles [32]. However, in Kevenaar's study, no difference between the AMH levels of 4-and 8-month-old mice was observed.…”

Anti-Müllerian hormone and polycystic ovary syndrome: a mountain too high?

“…In mice, the higher production of AMH by small antral follicles reflected the remaining follicle pool (Kevenaar et al 2006). Women of !25 years of age had higher serum AMH concentrations than those aged 35 years and above (Piltonen et al 2005), and when women were followed longitudinally for a period of between 1 and 7 years, there was a decrease in serum AMH levels, with levels becoming undetectable when menopause was reached (Piltonen et al 2005).…”

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age

“…Thus, AMH seems to downregulate two important steps of follicular development: follicle recruitment and cyclic selection for dominance [9,10]. Mouse studies have shown that AMH serum levels reflect the size of the primordial follicle pool and its reduction with aging [13,27]. In addition, human studies have shown that AMH directly correlates with the number of antral follicles assessed by ultrasound [5] and FSH, inhibin-B and estradiol [11].…”