PTEN and FOXO3 expression in the prenatal and postnatal human ovary

Albamonte, María Itatí; Calabro, Lara Yasmin; Albamonte, Mirta S.; Zuccardi, Luis; Stella, Inés; Halperín, Julia; Vitullo, Alfredo Daniel

doi:10.1007/s10815-020-01790-x

Cited by 12 publications

(8 citation statements)

References 28 publications

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“…Foxo3 and Fshr are also mainly regulated by miRNAs. Foxo3 is involved in the apoptosis of granulosa cells [ 58 ] and involved in the early development of follicles on its own [ 59 ] or with other genes [ 60 ]. Foxo3 interacts with mmu-miR-153-3p, which is known to suppress tumor growth in ovarian carcinoma [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

Kim

et al. 2021

IJMS

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Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

Kim

et al. 2021

IJMS

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“…Furthermore, whether iPGCs were induced by iPSCs or ESCs, the ovarian steroidogenic-related genes CYP19A1 , CYP17A1 , and FSHR were significantly increased, these genes have been linked to syndromic primary ovarian insufficiency (POI) [ 39 ], as have other supporting germ cell development genes such as FIGLA , DAZL , and IFITM3 . Meanwhile, the function of other differentially-expressed genes ranged from ovarian somatic cell activation to primordial follicles formation and development, such as YAP1 [ 40 ], BMP4 [ 41 ] and FOXO3 [ 42 ]. These findings imply that the formation of iPGCs is accompanied by the development of follicles.…”

Section: Discussionmentioning

confidence: 99%

Oocyte Arrested at Metaphase II Stage were Derived from Human Pluripotent Stem Cells in vitro

Wang

et al. 2023

Stem Cell Rev and Rep

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Initiation of meiosis is the most difficult aspect of inducing competent oocytes differentiation from human stem cells in vitro. Human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) were cultured with follicle fluid, cytokines and small molecule to induced oocyte-like cells (OLCs) formation through a three-step induction procedure. Expression of surface markers and differentiation potential of germ cells were analyzed in vitro by flow cytometry, gene expression, immunocytochemistry, western blotting and RNA Sequencing. To induce the differentiation of hiPSCs into OLCs, cells were firstly cultured with a primordial germ cell medium for 10 days. The cells exhibited similar morphological features to primordial germ cells (PGCs), high expressing of germ cell markers and primordial follicle development associated genes. The induced PGCs were then cultured with the primordial follicle-like cell medium for 5 days to form the induced follicle-like structures (iFLs), which retained both primordial oocytes-like cells and granulosa-like cells. In the third step, the detached iFLs were harvested and transferred to the OLC-medium for additional 10 days. The cultured cells developed cumulus-oocyte-complexes (COCs) structures and OLCs with different sizes (50–150 μm diameter) and a zona pellucida. The in vitro matured OLCs had polar bodies and were arrested at metaphase II (MII) stage. Some OLCs were self-activated and spontaneously developed into multiple-cell structures similar to preimplantation embryos, indicating that OLCs were parthenogenetically activated though in vitro fertilization potential of OLCs are yet to be proved. in vitro maturation of OLCs derived from hiPSCs provides a new means to study human germ cell formation and oogenesis. Graphical Abstract

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“…AKT is then phosphorylated and translocated to the nucleus, where it in turn phosphorylates the transcriptional factor forkhead box O (FOXO), resulting in its export into the cytoplasm. After translocation, inactive FOXO ceases its inhibitory influence over follicle growth [ 84 , 85 ]. Mammalian target of rapamycin complex (mTORC), another AKT downstream effector, is also involved in early-stage follicle activation and development.…”

Section: Follicle Activation: From Pmfs To Secondary Folliclesmentioning

confidence: 99%

Comprehensive Review of In Vitro Human Follicle Development for Fertility Restoration: Recent Achievements, Current Challenges, and Future Optimization Strategies

Vitale,

Dolmans

2024

JCM

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Ovarian tissue cryopreservation (OTC) and subsequent transplantation (OTT) is a fertility preservation technique widely offered to prepubertal girls and young fertile women who need to undergo oncological treatment but are at a high risk of infertility. However, OTT is not considered safe in patients with certain diseases like leukemia, Burkitt’s lymphoma, and ovarian cancer because of the associated risk of malignant cell reintroduction. In vitro follicle development has therefore emerged as a promising means of obtaining mature metaphase II (MII) oocytes from the primordial follicle (PMF) pool contained within cryopreserved ovarian tissue, without the need for transplantation. Despite its significant potential, this novel approach remains highly challenging, as it requires replication of the intricate process of intraovarian folliculogenesis. Recent advances in multi-step in vitro culture (IVC) systems, tailored to the specific needs of each follicle stage, have demonstrated the feasibility of generating mature oocytes (MII) from early-stage human follicles. While significant progress has been made, there is still room for improvement in terms of efficiency and productivity, and a long way to go before this IVC approach can be implemented in a clinical setting. This comprehensive review outlines the most significant improvements in recent years, current limitations, and future optimization strategies.

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PTEN and FOXO3 expression in the prenatal and postnatal human ovary

Cited by 12 publications

References 28 publications

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

Oocyte Arrested at Metaphase II Stage were Derived from Human Pluripotent Stem Cells in vitro

Comprehensive Review of In Vitro Human Follicle Development for Fertility Restoration: Recent Achievements, Current Challenges, and Future Optimization Strategies

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