Control of primordial follicle recruitment by anti-mullerian hormone in the mouse ovary

  • Durlinger A
  • Kramer P
  • Karels B
 et al. 
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Abstract

Thedimeric glycoprotein anti-Mu ¨ llerianhormone(AMH)is amem- ber of the transforming growth factor- ? superfamily of growth and differentiation factors. During male fetal sex differentiation, AMH is produced by Sertoli cells and induces degeneration of the Mu ¨ llerian ducts, which form the anlagen of part of the internal female genital system. In females, AMH is produced by the ovary, but only postna- tally. The function of AMH in the ovary is, however, still unknown. FemaleAMHnull mice were reported to be fertile, with normal litter size, but this does not exclude amoresubtle function for ovarianAMH. To investigate the function of AMH in the ovary, the complete follicle population was determined in AMH null mice, in mice het- erozygous for the AMH null mutation, and in wild-type mice of dif- ferent ages: 25 days, 4 months, and 13 months. In the present study we found that ovaries of 25-day- and 4-month-oldAMHnull females, compared to those of wild-type females, contain more preantral and small antral follicles. In addition, in 4- and 13-month-old AMH null females, smaller numbers of primordial follicles were found. Actually, in 13-month-old AMH null females, almost no primordial follicles could be detected, coinciding with a reduced number of preantral and small antral follicles in these females. In almost all females heterozy- gous for theAMHnull mutation the number of follicles fell in between the numbers found in wild-type and AMH null females. In 4-month- old AMH null females serum inhibin levels were higher and FSH levels were lower compared to those in wild-type females. In contrast, inhibin levels were lower in 13-month-old AMH null females, and FSH levels were unchanged compared to those in wild-type females. Furthermore, the weight of the ovaries was twice as high in the 4-month-oldAMHnull females as in age-matched wild-type females. We conclude that AMH plays an important role in primordial follicle recruitment, such that more primordial follicles are recruited in AMH null mice than in wild-type mice; the mice heterozygous for the AMH null mutation take an in-between position. Consequently, the ovaries of AMH null females and those of females heterozygous for the AMH null mutation will show a relatively early depletion of their stock of primordial follicles. The female AMH null mouse may thus provide a useful model to study regulation of primordial follicle recruitment and the relation between follicular dynamics and ovarian aging.

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