Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine

Kushnir, Vitaly A.; Seifer, David B.; Barad, David H.; Sen, Aritro; Gleicher, Norbert

doi:10.1007/s10815-017-0977-4

Cited by 46 publications

(33 citation statements)

References 94 publications

(112 reference statements)

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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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“…The pituitary gland is located outside the blood-brain barrier unlike the hypothalamus (Nussey and Whitehead 2001); therefore, the AMHR2 on gonadotrophs may bind AMH secreted from preantral and small antral follicles. Our data suggested that AMH, like the other TGF-β family members such as inhibin and activin (Kushnir et al 2017), can affect FSH secretion from gonadotrophs. However, little is known about the changes occurring in the blood AMH concentration during the estrous cycle in ruminants (Pfeiffer et al 2014; Koizumi and Kadokawa 2017).…”

Section: Discussionmentioning

confidence: 62%

Anti-Müllerian hormone receptor type 2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion

Kereilwe

Pandey

Borromeo

et al. 2018

Reprod. Fertil. Dev.

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Preantral and small antral follicles may secret anti-Müllerian hormone (AMH) to control gonadotrophin secretion from ruminant gonadotrophs. The present study investigated whether the main receptor for AMH, AMH receptor type 2 (AMHR2), is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion. Expression of AMHR2 mRNA was detected in anterior pituitaries (APs) of postpubertal heifers using reverse transcription-polymerase chain reaction. An anti-AMHR2 chicken antibody was developed against the extracellular region near the N-terminus of bovine AMHR2. Western blotting using this antibody detected the expression of AMHR2 protein in APs. Immunofluorescence microscopy using the same antibody visualised colocalisation of AMHR2 with gonadotrophin-releasing hormone (GnRH) receptor on the plasma membrane of gonadotrophs. AP cells were cultured for 3.5 days and then treated with increasing concentrations (0, 1, 10, 100, or 1000pgmL-1) of AMH. AMH (10-1000pgmL-1) stimulated (P<0.05) basal FSH secretion. In addition, AMH (100-1000pgmL-1) weakly stimulated (P<0.05) basal LH secretion. AMH (100-1000pgmL-1) inhibited GnRH-induced FSH secretion, but not GnRH-induced LH secretion, in AP cells. In conclusion, AMHR2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion.

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“…This includes research in better understanding of the genetic and environmental determinants of the AMH levels, molecular signaling pathways, and its interactome. Further, as there is an ongoing research in developing AMH analogues, understanding and examining the effect of any such analogues on non-reproductive systems will also be important 37 .…”

Section: Discussionmentioning

confidence: 99%

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

Kadariya

Kurbanova

Qayyum

2019

Sci Rep

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While serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with allcause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999-2004). We used survey weight-adjusted linear regression to examine the association between AMH and cRp without and with adjustment for age, race, body mass index (BMi), smoking, hypertension, diabetes, cholesterol, glomerular filtration rate (GFR), testosterone, androstenedione, and sex hormone binding globulin. Of the 949 men, 212 (22%) were elderly, 493 (52%) Caucasian, 254 (27%) current smokers, 100 (10%) diabetics, and 312 (33%) had hypertension. Mean (SD) AMH was 8.4 (7.2) ng/mL and median (IQR) CRP level was 0.17 (3) mg/L. Using linear regression, each 10 ng/mL rise in AMH was associated with 0.09 mg/ dL (95%CI = −0.14 to −0.03; p = 0.002) decrease before and 0.08 mg/dL (95%CI = −0.13 to −0.02; p = 0.004) decrease in CRP after adjusting for potential confounders. Similarly, men in the highest quartile of AMH had significantly lower CRP compared to those in the lowest quartile (unadjusted difference = −0.19 mg/dL; 95%CI = −0.31 to −0.06; p = 0.006, adjusted difference = −0.16 mg/dL; 95%CI = −0.3 to −0.01; p = 0.035). We found an independent, robust, and inverse association between CRP and AMH in men. Effect of AMH on mortality may be through amelioration of inflammation. Anti-mullerian hormone (AMH), is a glycoprotein belonging to the transforming growth factor-beta (TGF-β) superfamily. It is highly expressed in male fetal testis where it is responsible for regression of the mullerian duct. AMH remains elevated until puberty in men and rapidly declines during transition to the adulthood 1,2. While the role of the persistence of AMH during adulthood is unclear, the presence of AMH-specific receptor (AMHRII) in several organs (such as adrenal gland, liver, lung, skeletal muscle, and spleen) suggests that AMH may play a role during adult life beyond the development of reproductive system 3. In fact, epidemiological studies have demonstrated that serum AMH levels were inversely associated with cardiovascular events in elderly male, with infra-renal aortic diameter, and with all-cause mortality in men 4-6. However, the mechanisms underlying of these associations are not known. Growing body of evidence suggests that inflammation plays a critical role in the initiation and progression of atherosclerosis, chronic pulmonary disease (including COPD), and malignancy 7-9. Several studies have reported that serum c-reactive protein (CRP), an inflammatory biomarker, has the ability to predict cardiovascular disease, lung disease, cancer, and all-cause mortality risk in general population 10,11. In one study, serum AMH levels were negatively associated with in...

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Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine

Cited by 46 publications

References 94 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

Anti-Müllerian hormone receptor type 2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion

Association of Anti-Mullerian Hormone with C-Reactive Protein in Men

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