AMH mutations with reduced in vitro bioactivity are related to premature ovarian insufficiency

Mercadal, B. Alvaro; Imbert, R; Demeestere, Isabelle; Gervy, Christine; Leener, Anne De; Englert, Yvon; Costagliola, Sabine; Delbaere, Anne

doi:10.1093/humrep/dev042

Cited by 55 publications

(29 citation statements)

References 31 publications

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“…Therefore, the age-related increase in primordial follicle activation may arise from a reduction in inhibitory signals rather than an increase in activation-promoting regulators. This is further supported by mutations in the AMH and AMHR2 genes that are associated with primary ovarian insufficiency or decreased age at menopause (Kevenaar et al 2007, Park et al 2014, Alvaro Mercadal et al 2015. Across the lifespan, increased rates of primordial follicle activation tend to coincide with lower levels of inhibitors of primordial follicle activation, including AMH.…”

Section: Amh Expression Patterns Are Consistent With Primordial Follimentioning

confidence: 91%

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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Section: Amh Expression Patterns Are Consistent With Primordial Follimentioning

confidence: 91%

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

Pankhurst

2017

Journal of Endocrinology

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“…In chicken, the expression level of AMH was related to the growth of small follicles [37]. Several evidence has also shown that AMH inhibited the activation of primordial follicles [38], attenuated the rate of follicular growth [39] and inhibited follicular recruitment [40], suggesting the inhibitory action of AMH in the selection and growth of small follicles. It was also found that the expression level of AMH in GCs of the 4–10 mm follicles was higher than that in those of the F5–F1 follicles, suggesting that AMH might play a negative role in geese follicle recruitment and selection.…”

Section: Discussionmentioning

confidence: 99%

Promoter Identification and Transcriptional Regulation of the Goose AMH Gene

Yang

Deng

Chen

et al. 2019

Animals

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Simple SummaryAnti-Müllerian hormone (AMH) plays a vital role in the development of follicles. We found that the cloning nucleotide sequence of AMH was high homology in geese with other species. Several regulatory elements were identified and transcriptional factors were predicted in the AMH promoter sequence. Through a double-luciferase reporter assay, potential regulatory relationship spanning from −637 to −87 bp were identified. In addition, the mRNA expression of AMH gradually decreased during the development of follicles in geese. In the Chinese hamster ovary (CHO) cell line, the luciferase activity significantly increased by co-expression of AMH and GATA-4. However, when the binding sites of GATA-4 to the promoter of AMH were mutated, the luciferase activity significantly decreased. These results indicated that the transcription of AMH was activated by GATA-4 to inhibit the development of follicles in geese.AbstractAnti-Müllerian hormone (AMH) is recognized as a reliable marker of ovarian reserve. However, the regulatory mechanism of goose AMH gene remains poorly understood. In the present study, both the full-length coding sequence (CDS) and promoter sequence of goose AMH have been cloned. Its CDS consisted of 2013 nucleotides encoding 670 amino acids and the amino acid sequence contained two structural domain: AMH-N and transforming growth factor beta (TGF-β) domain. The obtained promoter sequence spanned from the −2386 bp to its transcription start site (ATG). Core promoter regions and regulatory elements were identified as well as transcription factors were predicted in its promoter sequence. The luciferase activity was the highest spanning from the −331 to −1 bp by constructing deletion promoter reporter vectors. In CHO cells, the luciferase activity significantly increased by co-expression of AMH and GATA binding protein 4 (GATA-4), while that significantly decreased by mutating the binding sites of GATA-4 located in the −778 and −1477 bp. Results from quantitative real-time polymerase chain reaction (qPCR) indicated that levels of AMH mRNA in geese granulosa layers decreased gradually with the increasing follicular diameter. Taken together, it could be concluded that the transcriptional activity of AMH was activated by GATA-4 to inhibit the development of small follicles in goose.

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“…Plasma AMH level is one of the criteria used to diagnose polycystic ovary syndrome (PCOS) 20 , which results in an anovulation, and subsequent infertility, in women of reproductive age. Besides, AMH is an excellent marker of ovarian reserve, as a decrease in AMH level is typically accompanied by ovarian senescence 21 , 22 . Also, AMH can inhibit the process of primordial follicle recruitment and follicle development 22 .…”

Section: Discussionmentioning

confidence: 99%

“…Besides, AMH is an excellent marker of ovarian reserve, as a decrease in AMH level is typically accompanied by ovarian senescence 21 , 22 . Also, AMH can inhibit the process of primordial follicle recruitment and follicle development 22 .…”

Section: Discussionmentioning

confidence: 99%

Genetic Architecture and Candidate Genes Identified for Follicle Number in Chicken

Shen

Sun

et al. 2017

Sci Rep

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Follicular development has a major impact on reproductive performance. Most previous researchers focused on molecular mechanisms of follicular development. The genetic architecture underlying the number of follicle, however, has yet not to be thoroughly defined in chicken. Here we report a genome-wide association study for the genetic architecture determining the numbers of follicles in a large F2 resource population. The results showed heritability were low to moderate (0.05–0.28) for number of pre-ovulatory follicles (POF), small yellow follicles (SYF) and atresia follicles (AF). The highly significant SNPs associated with SYF were mainly located on GGA17 and GGA28. Only four significant SNPs were identified for POF on GGA1. The variance partitioned across chromosomes and chromosome lengths had a linear relationship for SYF (R2 = 0.58). The enriched genes created by the closest correspondent significant SNPs were found to be involved in biological pathways related to cell proliferation, cell cycle and cell survival. Two promising candidate genes, AMH and RGS3, were suggested to be prognostic biomarkers for SYF. In conclusion, this study offers the first evidence of genetic variance and positional candidate genes which influence the number of SYF in chicken. These identified informative SNPs may facilitate selection for an improved reproductive performance of laying hens.

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AMH mutations with reduced in vitro bioactivity are related to premature ovarian insufficiency

Abstract: The study was performed thanks to funding from the 'Fondation Erasme'. No conflicts of interest are declared.

Cited by 55 publications

References 31 publications

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

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

Promoter Identification and Transcriptional Regulation of the Goose AMH Gene

Genetic Architecture and Candidate Genes Identified for Follicle Number in Chicken

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