Positive cross talk between FOXL2 and antimüllerian hormone regulates ovarian reserve

Capsule:
AMH is an endogenous target gene of FOXL2, and the two factors collaboratively work to reserve ovarian follicles.

Authors:
Mira Park, Ph.D., Dae-Shik Suh, M.D., Kangseok Lee, Ph.D., Jeehyeon Bae, Ph.D.

Volume 102, Issue 3, Pages 847-855

Abstract:

Objective:
To demonstrate interregulation between FOXL2 and antimüllerian hormone (AMH) in ovarian folliculogenesis.

Design:
Cell culture and animal study.

Setting:
University research laboratory.

Animal(s):
Five-week-old B6C3F1 mice.

Interventions(s):
Molecular analysis and in vivo mouse experiment were performed to demonstrate that AMH is a target gene of FOXL2 in the ovary.

Main Outcome Measure(s):
To determine whether FOXL2 transactivates AMH, luciferase reporter assay, electrophoretic mobility shift assay, and chromatin immuniprecipitation were conducted. Using an in vivo nucleic acid delivery system, the expression of AMH and/or FOXL2 was modulated in the mouse, and the ovaries were histologically analyzed.

Result(s):
AMH is an endogenous target gene of FOXL2. In contrast, mutated FOXL2s found in premature ovarian failure patients were defective in their ability to activate AMH transcription in human granulosa cells. In vivo mouse gene delivery experiments revealed that Amh-knockdown accelerated follicle growth; however, the acceleration was prevented by ectopic expression of FOXL2.

Conclusion(s):
AMH and FOXL2 collaboratively work to reserve ovarian follicles.

  • sir 王

    机制问题没用探讨 The mechanism is not investgated in the article ,which i was very interested。

  • Reshef Tal

    This is a very interesting study which addresses an
    important yet understudied area, the regulation of AMH expression in the ovary.
    The authors show that AMH expression is increased by FOXL2 in-vitro and in-vivo
    using an elegant mouse model, demonstrating that FOXL2 could mitigate the
    follicular growth and depletion induced by AMH downregulation. These
    data nicely corroborate other animal studies showing that either AMH knockout or
    FOXL2 knockout lead to rapid follicular depletion and POF. Since AMH is
    well-known to be upregulated in PCOS and the authors show here that FOXL2 leads
    to an increase in ovarian AMH expression above normal levels, it raises the
    question whether FOXL2 may have a potential role in PCOS pathogenesis. Did the
    authors examine their mice overexpressing FOXL2 for such features and what is
    their opinion regarding this possibility?

  • Shvetha Zarek

    Kudos to the authors for robust experiments that provide further insight into the mechanisms of follicular pool depletion and the interaction of FOXL2 and AMH. The authors should be commended on providing “bedside to bench” evidence demonstrating that known FOXL2 mutant sequences in patients with BPES I and POI failed to activate AMH expression.

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