Anti-Müllerian Hormone (AMH) Treatment Enhances Oocyte Quality, Embryonic Development and Live Birth Rate
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ABSTRACT: In this study, we determine for the first time, the effects of AMH priming on oocyte quality and competence, early embryonic development, and fertility.
Project description:The current study was designed to investigate the actions of Anti-Müllerian Hormone (AMH) on primordial follicle assembly. Ovarian primordial follicles develop from the breakdown of oocyte nests during fetal development for the human and immediately after birth in rodents. AMH was found to inhibit primordial follicle assembly, decrease the initial primordial follicle pool size and promote the persistence of small oocyte nests in a rat ovarian organ culture. The AMH expression was found to be primarily in the stromal tissue of the ovaries at this period of development, suggesting a stromal-epithelial cell interaction for primordial follicle assembly. AMH was found to promote alterations in the ovarian transcriptome during primordial follicle assembly with over 200 genes with altered expression. A gene network was identified suggesting a potential central role for the Fgf2/Nudt6 antisense transcript in the follicle assembly process. A number of signal transduction pathways are regulated by AMH actions on the ovarian transcriptome, in particular the transforming growth factor – beta (TGFß) signaling process. AMH is the first hormone/protein shown to have an inhibitory action on primordial follicle assembly. Due to the critical role of the primordial follicle pool size for female reproduction, elucidation of the factors, such as AMH, that regulate the assembly process will provide insights into potential therapeutics to manipulate the pool size and female reproduction. We used microarrays to determine genes expressed differentially between control and AMH (Anti-Müllerian Hormone) treated P0 ovary
Project description:Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved. This study is a repetition of a previous study (GEO accession .no.: GSE56737) at the concentration of 50 ng/mL. The overall design are almost similar to GSE56737 except that it was performed in quadruplicate. Preantral to small antral follicles were collected from dissected ovaries from six to eight weeks old female C57BL/6Tac mice. Twelve hour as well as 24 hour experiments were performed in one fixed concentration of AMH and an untreated control. The experiments were performed in quadroplicate. In total 16 samples: 2 x conc. (control and 50 ng/ml AMH), 2 x time points, 4 x experiments (quadroplicate). Samples are pairwise comparable within each experiment, that is, sample 1-2 or 3-4 or 5-6 or 7-8 or 9-10 or 11-12 or 13-14 or 15-16. Data are also comparable groupwise; (1,5,9,13) vs (2,6,10,14) or (3,7,11,15) vs (4,8,12,16).
Project description:Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved. This study is a repetition of a previous study (GEO accession .no.: GSE56737) at the concentration of 50 ng/mL. The overall design are almost similar to GSE56737 except that it was performed in quadruplicate.
Project description:Circadian clocks temporally orchestrate the behavioural and physiological rhythms. The core molecules establishing the circadian clock are clear; however, the critical signalling pathways that cause or favour the homeostasis are poorly understood. Here, we report that anti-Müllerian hormone (Amh)-mediated signalling plays an important role in sustaining circadian homeostasis in zebrafish. Remarkably, amh knockout dampens molecular clock oscillations and disrupts both behavioural and hormonal circadian rhythms, which were recapitulated in bmpr2a null mutants. Somatotropes and gonadotropes were identified as Amh-positive pituitary cell populations. Single-cell transcriptome analysis further revealed a lineage-specific regulation of pituitary clock by Amh. Moreover, Amh-induced effect on clock gene expression could be abolished by blocking Smad1/5/9 phosphorylation and bmpr2a knockout. Mechanistically, Amh binds to its receptors, Bmpr2a/Bmpr1bb, which in turn activate Smad1/5/9 by phosphorylation and promote circadian gene expression. Our findings reveal a key hormone signalling pathway for circadian homeostasis in zebrafish with implications for rhythmic organ functions and circadian health.
Project description:Research Question: Does over-expression of AMH lead to changes in oocyte gene expression in mice? Design: Naturally ovulated oocytes were dissected from the oviduct of wild-type, and AMH-overexpressing (Thy1.2-AMHTg/0) mice and single oocytes underwent transcriptome sequencing (n=11 and n=10, respectively). Results: Oocytes from Thy1.2-AMHTg/0 females displayed 39 significantly expressed differentially expressed genes (DEGs) compared to wild-type mouse oocytes. The most prominent gene expression changes were a 70-fold increase in Rpsa3a, a 22-fold increase in Hormad1 and a 5.6-fold increases in Fnip2 in the oocytes from Thy1.2-AMHTg/0 mice. Gene ontology analysis indicated that among the DEGs, the most enriched pathways were mitochondrial genes and DNA repair genes. Conclusions: These data show that overexpression of AMH, through its actions on granulosa cells, can lead to changes in the expression of specific genes in mouse oocytes.
Project description:Circadian clocks temporally orchestrate the behavioural and physiological rhythms. The core molecules establishing the circadian clock are clear; however, the critical signalling pathways that cause or favour the homeostasis are poorly understood. Here, we report that anti-Müllerian hormone (Amh)-mediated signalling plays an important role in sustaining circadian homeostasis in zebrafish. Remarkably, amh knockout dampens molecular clock oscillations and disrupts both behavioural and hormonal circadian rhythms, which were recapitulated in bmpr2a null mutants. Somatotropes and gonadotropes were identified as Amh-positive pituitary cell populations. Single-cell transcriptome analysis further revealed a lineage-specific regulation of pituitary clock by Amh. Moreover, Amh-induced effect on clock gene expression could be abolished by blocking Smad1/5/9 phosphorylation and bmpr2a knockout. Mechanistically, Amh binds to its receptors, Bmpr2a/Bmpr1bb, which in turn activate Smad1/5/9 by phosphorylation and promote circadian gene expression. Our findings reveal a key hormone signalling pathway for circadian homeostasis in zebrafish with implications for rhythmic organ functions and circadian health.
Project description:Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved. Preantral to small antral follicles were collected from dissected ovaries from six to eight weeks old female C57BL/6Tac mice. Twelve hour as well as 24 hour experiments were performed in two different concentrations of AMH. The experiments were performed in triplicate. In total 18 samples: 3 x conc. of AMH, 2 x time points, 3 x experiments (triplicate). Samples are comparable within each experiment, that is, sample 1-3 or 4-6 or 7-9 or 10-12 or 13-15 or 16-18.
Project description:Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved.