Accelerated ovarian reserve depletion in female anti-Müllerian hormone knockout mice has no effect on lifetime fertility†

Abstract

Anti-Müllerian hormone (AMH) inhibits the activation of primordial follicles in the ovary. This causes an increased rate of ovarian reserve depletion in Amh-/- mice. The depletion of the ovarian reserve is responsible for the onset of menopause but age-related infertility occurs in advance of ovarian reserve depletion. To determine whether accelerated loss of primordial follicles leads to earlier onset infertility, Amh-/- and Amh+/+ females were paired with Amh+/+ stud males and birth rates were recorded across the females' reproductive lifespan. The number of primordial follicles remaining in the ovaries of Amh-/- and Amh+/+ females were quantified in two cohorts at 11-12 and 12-13 months of age. As expected, the ovarian reserve in the Amh-/- females became depleted approximately 1 month earlier than Amh+/+ females. However, no difference was observed in the cumulative number of births over the lifespan, nor were there any differences in mean littersize at any age. It is possible that the reproductive lifespan of mice is too short for sufficient divergence of primordial follicles numbers to cause differences in Amh-/- and Amh+/+ female fertility. An alternative explanation contradicts current thinking; the function of AMH may be unrelated to the longevity of the reproductive lifespan in female mice.

Keywords: anti-Müllerian hormone; corpus luteum; female infertility; fertility; litter size; null mutation/knockout; ovary.