Anti-Müllerian Hormone Attenuates the Effects of FSH on Follicle Development in the Mouse Ovary

Abstract

Although ovarian follicle growth is under the influence of many growth factors and hormones of which FSH remains one of the most prominent regulators. Therefore, factors affecting the sensitivity of ovarian follicles to FSH are also important for follicle growth. The aim of the present study was to investigate whether anti-Müllerian hormone (AMH) has an inhibitory effect on follicle growth by decreasing the sensitivity of ovarian follicles to FSH. Furthermore, the combined action of AMH and FSH on ovarian follicle development was examined. Three different experiments were performed. Using an in vitro follicle culture system it was shown that FSH-stimulated preantral follicle growth is attenuated in the presence of AMH. This observation was confirmed by an in vivo experiment showing that in immature AMH-deficient females, more follicles start to grow under the influence of exogenous FSH than in their wild-type littermates. In a third experiment, examination of the follicle population of 4-month-old wild-type, FSH beta-, AMH-, and AMH-/FSH beta-deficient females revealed that loss of FSH expression has no impact on the number of primordial and preantral follicles, but the loss of inhibitory action of AMH on the recruitment of primordial follicles in AMH-deficient mice is increased in the absence of FSH. In conclusion, these studies show that AMH inhibits FSH-stimulated follicle growth in the mouse, suggesting that AMH is one of the factors determining the sensitivity of ovarian follicles for FSH and that AMH is a dominant regulator of early follicle growth.

Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile49Ser) and Anti-Müllerian hormone type II receptor (AMHRII −482 A>G) as genetic markers in assisted reproduction technology

“…Others suggested that AMH inhibits FSH action in the ovary [33]. This suggestion was based on studies showing that AMH decreased aromatase activity in the fetal ovary [34] and that follicles from AMH knock-out mice were more sensitive to FSH [35]. Although the exact physiological role of AMH is poorly understood, in vivo and in vitro studies in mice and in vitro studies in human demonstrated that AMH inhibits the primordial follicle recruitment and cyclic selection [11,12,35,36].…”

“…This suggestion was based on studies showing that AMH decreased aromatase activity in the fetal ovary [34] and that follicles from AMH knock-out mice were more sensitive to FSH [35]. Although the exact physiological role of AMH is poorly understood, in vivo and in vitro studies in mice and in vitro studies in human demonstrated that AMH inhibits the primordial follicle recruitment and cyclic selection [11,12,35,36]. The presence of the Ile49Ser polymorphism in the gene encoding AMH may alter its bioactivity and function in the ovary, as Kevenaar et al have already mentioned [18].…”

“…Our data shows that FSH concentration in peripheral blood is significantly lower in non-carriers of AMH polymorphism with more than two previous IVF attempts and this may suggest a better ovulation induction outcome, even in this subgroup of patients. Taking into account that AMH affects the modification of the FSH sensitivity of small antral follicles in the process of cyclic selection [11,35], we can hypothesize that there is a biological path among FSHR-AMH/AMHRII complex that leads to a regulatory step of folliculogenesis.…”

Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro

“…The molecular mechanisms that determine the survival and growth potential of preantral follicles are not clear. Studies in mice suggest that AMH plays an essential role during follicular development by inhibiting preantral follicle growth and antral follicle maturation [8]. Although not documented in studies using rodents and domestic animals, the levels of AMH protein varied in marmoset preantral follicles based on immunohistochemical analysis [9].…”

Factors Influencing the Biochemical Markers for Predicting Mammalian Oocyte Quality

“…58, No 4, 2012 OLA and SUN 386 their activation, primordial follicles are repressed by factors that have not been conclusively identified. Some of the already known repressors include anti-Mullerian hormone (AMH), which is suspected to block the follicle's sensitivity to FSH [9,10]; Sohlh2, a factor implicated in the maintenance and differentiation of primordial oocyte [11]; and Pten, which blocks the phosphatidylinositol 3-kinase pathway [12,13]. Follicle activation refers to the recruitment of some of the dormant primordial follicles into the growing pool that are destined for ovulation.…”