Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development

Hayes, Emily; Kushnir, Vitaly A.; Ma, Xiaoting; Biswas, Ashim Kumar; Prizant, Hen; Gleicher, Norbert; Sen, Aritro

doi:10.1016/j.mce.2016.05.019

Cited by 83 publications

(69 citation statements)

References 41 publications

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“…As such, we explored AMH synthesis in our experimental animals that received stem cell injections, observing a concurrent increase in AMH synthesis. The observation of restored contralateral ovarian function along with the finding of elevated AMH synthesis by the differentiated stem cells, collectively supports the idea that AMH may be important in mediating the observed restoration of ovarian function in these studies [33][34][35][36][37] . Together, these data suggest the feasibility of patients providing their own cells to restore ovarian function, synthesize bioidentical hormones, and restore fertility by neogametogenesis.…”

Section: Discussionsupporting

confidence: 79%

“…The precise paracrine mechanism of action remains elusive for those stem cells, however, AMH proves to be a promising candidate molecule given its preventative effect on follicular atresia and apoptosis 36,37 . AMH is exclusively synthesized by granulosa cells during the early stages of follicular development 38 , and AMH serum concentration is an important measure of ovarian reserve 39 .…”

Section: Discussionmentioning

confidence: 99%

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iPSC-Derived Ovarian Tissue Restores Ovarian Function in Subfertile Mice and After Gonadotoxic Chemotherapy

Elias

et al. 2019

Preprint

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Running Title: iPSC-based restoration of ovarian function following gonadotoxic chemotherapy iPSC -based restoration of ovarian function following gonadotoxic chemotherapy 2 Abstract Many oncologic therapies given to young women are gonadotoxic and associated with diminished ovarian reserve, increased risk of permanent sterility, and premature menopause. Previously, we reported the derivation of steroidogenic ovarian cells from induced pluripotent and embryonic stem cells. Derived cells not only produced reproductive hormones, but also displayed markers of ovarian tissue and primordial gametes. Here, we describe that human follicular fluid, when added to our stem cell differentiation system, enhances the steroidogenic potential of derived cells and increases the subpopulation of cells that differentiate to express the ovarian and germ cell markers GJA1 and ZP1, respectively. More importantly, using an in vivo model of chemotherapy-induced premature ovarian insufficiency in subfertile nude mice, we demonstrate that orthotopic implantation of these derived cells restores ovarian hormonal production and produces functional stem cell-derived germ cells. Collectively, these data support the hypothesis that stem cell-derived steroidogenic ovarian tissue could be used to promote neo-gametogenesis and treat premature menopause.iPSC -based restoration of ovarian function following gonadotoxic chemotherapy

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

iPSC-Derived Ovarian Tissue Restores Ovarian Function in Subfertile Mice and After Gonadotoxic Chemotherapy

Elias

et al. 2019

Preprint

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“…Accordingly, AMH −/− mice have enlarged pools of preantral and small antral follicles, but concomitant increases in atresia have a correcting influence on large antral follicle counts, which are equivalent to counts in wild-type mice (Durlinger et al 1999). Conservation of the ovarian reserve after injection of recombinant AMH into young mice has also been observed (Hayes et al 2016). Exogenous application of AMH inhibits primordial follicle activation in explant cultures of human, rat, mouse and goat ovary tissue (Durlinger et al 2002, Gigli et al 2005, Carlsson et al 2006, Nilsson et al 2007, Rocha et al 2016.…”

Section: :1mentioning

confidence: 87%

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

Pankhurst

2017

Journal of Endocrinology

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The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein.

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“…FOXO3A is expressed in the nucleus of PMFs and plays an essential role in the maintenance of PMF at a dormant state (1). This was highlighted in Foxo3a 2/2 mice, which exhibit a global follicular activation leading to oocyte death and early depletion of ovarian reserve (32). Moreover, it has been shown that phosphorylation of FOXO3A induces the protein nuclear export, leading to PMF activation (2).…”

Section: Discussionmentioning

confidence: 99%

AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide‐treated mice

et al. 2018

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The follicular ovarian reserve, constituted by primordial follicles (PMF), is established early in life, then keeps declining regularly along reproductive life. The maintenance of a normal female reproductive function implies the presence of a vast amount of dormant PMF. This process involves a continuous repression of PMF activation into early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the PI3K signaling pathway, and inhibiting factors such as anti-Müllerian hormone (AMH). Any disruption of this balance may induce follicle depletion and subsequent infertility. It has been recently proposed that cyclophosphamide (Cy), an alkylating agent commonly used for treating breast cancer, triggers PMF activation, further leading to premature ovarian insufficiency. Preventing chemotherapy-induced ovarian dysfunction might represent an interesting option for preserving optimal chances of natural or medically assisted conceptions after healing. The aim of the present study was to evaluate, in a model of Cy-treated pubertal mice, whether AMH administration might restrain PMF depletion. The counting of the total PMF number within mouse ovaries showed that recombinant AMH prevented Cy-induced PMF loss. Western blot analysis revealed activation of PI3K signaling pathway after Cy administration. After AMH injection, FOXO3A phosphorylation, a main actor of PMF activation, was significantly decreased. Taken together, these results support a protective role of AMH against Cy-induced follicular loss. We also provide evidence for a possible role of autophagy in the preservation of follicular pool reserve. Therefore, concomitant recombinant AMH administration during chemotherapy might offer a new option for preserving young patients' fertility.-Sonigo, C., Beau, I., Grynberg, M., Binart, N. AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide-treated mice.

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Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development

Cited by 83 publications

References 41 publications

iPSC-Derived Ovarian Tissue Restores Ovarian Function in Subfertile Mice and After Gonadotoxic Chemotherapy

iPSC-Derived Ovarian Tissue Restores Ovarian Function in Subfertile Mice and After Gonadotoxic Chemotherapy

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide‐treated mice

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