Stage-dependent actions of antimüllerian hormone in regulating granulosa cell proliferation and follicular function in the primate ovary

Abstract

Objective: To study the direct action and physiological role of antim€ ullerian hormone (AMH) in regulating ovarian follicular development and function in vivo in primates. Design: Animals were assigned to six treatment sequences in a crossover design study. Intraovarian infusion was performed during the follicular phase of the menstrual cycle with agents including: control vehicle; recombinant human AMH (rhAMH); and neutralizing anti-human AMH antibody (AMHAb). Before ovariectomy after the final treatment, the animals received intravenous injections of bromodeoxyuridine (BrdU). Setting: National primate research center. Animal(s): Adult female rhesus macaques (Macaca mulatta). Intervention(s): None. Main Outcome Measure(s): Cycle length, follicle cohorts, and serum steroid levels were assessed. Ovarian histology, as well as granulosa cell (GC) proliferation and oocyte viability, were evaluated. Result(s): In vehicle-infused ovaries, a dominant follicle was observed at midcycle E 2 peak. However, rhAMH-treated ovaries exhibited an increased number of small antral follicles, whereas AMHAb-treated ovaries developed multiple large antral follicles. Serum E 2 levels in the follicular phase decreased after rhAMH infusion and increased after AMHAb infusion. The rhAMH infusion increased serum T levels. Whereas early-growing follicles of rhAMH-treated ovaries contained BrdU-positive GCs, antral follicles containing BrdUpositive GCs were identified in AMHAb-treated ovaries. Autophagy was observed in oocytes of early-growing and antral follicles exposed to AMHAb and rhAMH, respectively. Conclusion(s): AMH enhanced early-stage follicle growth, but prevented antral follicle development and function via its stagedependent regulation of GC proliferation and oocyte viability. This study provides information relevant to the pathophysiology of ovarian dysfunction and the treatment of infertility. (Fertil Steril Sci Ò 2020;1:161-71. Ó2020 by American Society for Reproductive Medicine.

New AMH cutoff values for warning of decreased ovarian response based on MCL characteristics in young women: a retrospective study using a propensity score-matching analysis

“…In mouse experiments, researchers found that as AMH expression decreased, apoptotic granulosa cells increased, suggesting a positive correlation between AMH and the number of granulosa cells [ 18 ]. Studies have shown that AMH can increase the expression of stem cell factor/kit ligand [ 28 ] and can regulate the proliferation of granulosa cells in a phased manner to promote the growth of early follicles [ 29 ]. In addition, follicle size is the key indicator for successful follicle development [ 30 ], and ultrasound measurement of follicle size is a reliable parameter for making many clinical decisions.…”

Anti-Müllerian Hormone: A Molecular Key to Unlocking Polycystic Ovary Syndrome?

“…For example, in female rhesus monkeys, blocking AMH action within the ovary or in cell culture inhibits preantral/small antral follicle recruitment and enhances dominant follicle selection beyond the species-typical single preovulatory follicle; conversely, enriching AMH levels under similar conditions enhances preantral/small antral follicle recruitment and impairs dominant follicle selection. 11,12 AMH-enriched monkey ovaries, not surprisingly, start to accumulate overly numerous small antral follicles with impaired selection of a dominant follicle. 12 Whether such AMH-enriched, polyfollicular monkey ovaries progress into polycystic ovaries remains to be determined.…”

New AMH cutoff values for warning of decreased ovarian response based on MCL characteristics in young women: a retrospective study using a propensity score-matching analysis

“…In mouse experiments, researchers found that as AMH expression decreased, apoptotic granulosa cells increased, suggesting a positive correlation between AMH and the number of granulosa cells [12]. Studies have shown that AMH can increase the expression of stem cell factor/kit ligand [20] and can regulate the proliferation of granulosa cells in a phased manner to promote the growth of early follicles [21]. In addition, follicle size is the key indicator for successful follicle development [22], and ultrasound measurement of follicle size is a reliable parameter for making many clinical decisions.…”