Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro

Wang, Tianren; Yan, Liying; Yan, Jie; Lu, Cuiling; Xia, Xi; Yin, Tailang; Zhu, Xiaohui; Gao, Jiangman; Ding, Ting; Hu, Weihong; Guo, Hongyan; Li, Rong; Qiao, Jie

doi:10.1093/humrep/det465

Cited by 48 publications

(42 citation statements)

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“…5). These current findings are consistent with the results of a previous study that showed that HGF and bFGF promoted cell proliferation and delayed oocyte aging during culture in vitro [30, 31]. …”

Section: Discussionsupporting

confidence: 93%

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

Ding

Zou

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Human adipose-derived stem cells (hADSCs) are a potential therapeutic option for clinical applications because of their ability to produce cytokines and their capacity for trilineage differentiation. To date, few researchers have investigated the effects of hADSCs on natural ovarian aging (NOA). Methods: An NOA mouse model and human ovarian granule cells (hGCs) collected from individuals with NOA were prepared to assess the therapeutic effects and illuminate the mechanism of hADSCs in curing NOA. Enzyme-linked immunosorbent assay was used to detect the serum levels of sex hormones and antioxidative enzymes. The proliferation rate and marker expression level of hGCs were measured by flow cytometry (FACS). Cytokines were measured by a protein antibody array methodology. Western blot assays were used to determine the protein expression levels of SIRT1 and FOXO1. Results: Our results showed that hADSCs displayed therapeutic activity against ovarian function in an NOA mouse model, increasing the proliferation rate and marker expression level of hGCs. Furthermore, the yields of hADSC-secreted HGF and bFGF were higher than those of other growth factors. FACS showed that combination treatment with the growth factors HGF and bFGF more strongly promoted proliferation and inhibited apoptosis in hGCs than HGF or bFGF treatment alone. FACS and ELISA revealed that the combination treatment with both growth factors inhibited oxidative stress more forcefully than treatments with only one of these growth factors. In addition, protein assays demonstrated that combination treatment with both growth factors suppressed oxidative stress by up-regulating the expression of SIRT1 and FOXO1. Conclusion: These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism by which HGF and bFGF derived from hADSCs improved ovarian function during natural aging via reduction of oxidative stress by activating the SIRT1/FOXO1 signaling pathway.

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Section: Discussionsupporting

confidence: 93%

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

Ding

Zou

Wang

et al. 2018

Cell Physiol Biochem

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“…We developed an encapsulated in vitro follicle growth (eIVFG) culture system, which preserves 3D follicular structure with paracrine signaling maintained between oocyte, granulosa and theca cells (Kreeger et al, 2006;Tingen et al, 2011;Tagler et al, 2012;Hornick et al, 2013). In addition to murine follicles, success to date in the culture of larger mammalian species has been reported in the alginate system including follicles from dog, rhesus macaque, goat, baboon and human (Xu et al, 2009a(Xu et al, ,b, 2010(Xu et al, , 2011b(Xu et al, ,c, 2013aSongsasen et al, 2011;Camboni et al, 2013;Fisher et al, 2013;Araujo et al, 2014;Silva et al, 2014;Wang et al, 2014). Further, eIVFG has facilitated studies of inter-and intra-follicular mechanisms governing follicularphase processes including antrum formation, oocyte maturation and granulosa cell proliferation (Kreeger et al, 2006;West-Farrell et al, 2009;Hornick et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Engineering the ovarian cycle using in vitro follicle culture

et al. 2015

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study question: Can cultured follicles model the ovarian cycle, including follicular-and luteal-phase hormone synthesis patterns and ovulation?summary answer: Under gonadotrophin stimulation, murine follicles grown in an encapsulated three-dimensional system ovulate in vitro and murine and human follicle hormone synthesis mimics follicular and luteal phases expected in vivo.what is known already: Studies of the human ovary and follicle function are limited by the availability of human tissue and lack of in vitro models. We developed an encapsulated in vitro follicle growth (eIVFG) culture system, which preserves 3D follicular structure. Thus far, the alginate system has supported the culture of follicles from mice, dog, rhesus macaque, baboon and human. These studies have shown that cultured follicles synthesize steroid hormones similar to those observed during the follicular phase in vivo. study design, size, duration: Cultured murine follicles were treated with human chorionic gonadotrophin (hCG) and epidermal growth factor (EGF) and either assayed for luteinization or removed from alginate beads and assayed for ovulation. Human follicles were also cultured, treated with follicle-stimulating hormone (FSH), hCG and EGF to mimic gonadotrophin changes throughout the ovarian cycle, and culture medium was assayed for hormone production.participants/materials, setting, methods: Murine and human follicles were cultured in alginate hydrogel and hormone production [17b-estradiol, progesterone, inhibin A, inhibin B, activin A and anti-Müllerian hormone (AMH)] was quantified in medium by enzyme-linked immuno assay (ELISA). Human ovarian tissue was acquired from females between 6 and 34 years of age with a cancer diagnosis. These participants were undergoing ovarian tissue cryopreservation at National Physicians Cooperative sites as part of the Oncofertility Consortium.main results and the role of chance: When grown in this system, 96% of mouse follicles ovulated in response to hCG and released meiotically competent eggs. Ovulated follicles recapitulated transcriptional, morphologic and hormone synthesis patterns post-luteinizing hormone (LH/hCG). In addition to rodent follicles, individual human follicles secreted steroid and peptide hormones that mimicked the patterns of serum hormones observed during the menstrual cycle.limitations, reasons for caution: This was a descriptive study of an in vitro model of ovulation and the ovarian hormone cycle.The ovulation studies were limited to murine tissue and further studies are needed to optimize conditions using other species.wider implications of the findings: The eIVFG system reliably phenocopies the in vivo ovarian cycle and provides a new tool to study human follicle biology and the influence of cycling female hormones on other tissue systems in vitro. study funding/competing interest(s): This work was supported by NIH U54 HD041857, NIH U54 HD076188, NIH UH2 E5022920, NIH UH3 TR001207 and F30 AG040916 (R.M.S.). The content is solely the responsibility of the authors and do...

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“…Here, we demonstrated that a 3D culture technique utilizing alginate hydrogel (a system previously developed by others) [11, 39] sustained the ability of cat secondary and early antral follicles to grow and survive in vitro for up to 15 d. Furthermore, unlike in earlier cat studies [37, 38], some of the resident oocytes (up to 21%) recovered from donor follicles cultured in the 3D alginate system retained the capacity to resume meiosis and complete nuclear maturation. In that context, this alternative mode of incubation itself imparted advantages for incubating premature cat follicles, as it has for the mouse [7], human [9, 10, 40] and non-human primate [11, 12]. For the human, secondary follicles exposed to such conditions maintain a normal morphological structure, increase in size, and actually form an antral cavity by the 30 th day of culture [11].…”

Section: Discussionmentioning

confidence: 99%

Short-term hypertonic exposure enhances in vitro follicle growth and meiotic competence of enclosed oocytes while modestly affecting mRNA expression of aquaporin and steroidogenic genes in the domestic cat model

et al. 2017

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Using the domestic cat as a non-rodent, larger animal model, the objective of the present study was to determine the impact of a brief incubation in a hypertonic microenvironment on (1) ovarian follicle and oocyte growth in vitro, (2) developmental capacity of the resident oocyte, and (3) expression of aquaporin (AQP) genes in parallel with genes involved in the regulation of folliculogenesis. In Study 1: Secondary or early antral follicles encapsulated in alginate were allocated to one of three treatment groups: 1) culture in standard medium at 290 mOsm for 15 d (Control); 2) incubation in 350 mOsm medium for 1 h followed by culture in standard medium for 15 d (Hypertonic-1h); or 3) incubation in 350 mOsm medium for 24 h followed by incubation in standard medium for additional 14 d (Hypertonic-24h). After measuring follicle and oocyte diameters on Day 15, in vitro-grown oocytes were incubated for 24 h before assessing their nuclear status. In Study 2: secondary or early antral follicles were subjected to one of the three treatments: 1) culture in standard medium at 290 mOsm for 48 h; 2) incubation in 350 mOsm medium for 1 h followed by culture in standard medium for additional 47 h; or 3) incubation in 350 mOsm medium for 24 h followed by culture in standard medium for additional 24 h. At the end of the culture period, all follicles were assessed for mRNA level of Cyp17a1, Cyp19a1, Star (Steroidogenesis genes)AQP1, 3, 5, 7 and 8 as well as Fshr using qPCR. Freshly collected follicles also were subjected to gene expression analysis and served as ‘Non-cultured control’. Hypertonic-24h follicles grew larger (P < 0.05) than the control, whereas those in Hypertonic-1h group exhibited intermediate growth, especially when the culture started at the early antral stage. Oocytes in the Hypertonic-24h group were larger and resumed meiosis at a higher rate than in the other treatments. In vitro culture affected (P < 0.05) mRNA expression of Cyp19a1, Star, AQP1 and AQP7 in both secondary and early antral stage while FSHr was only affected in the former compared to the non-cultured control. Pre-incubating follicles in 350 mOsm medium for 24 h enhanced (P < 0.05) Star and AQP7 while decreasing (P < 0.05) AQP1 expression compared to the control in secondary follicles, but not in the early antral stage. In summary, short-term hypertonic exposure promoted cat follicle development in vitro (including the meiotic competence of the enclosed oocyte) possibly through a mechanism that does not involve water transport genes.

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Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro

Abstract: This work was supported by the National Basic Research Program of China (2011|CB944504, 2011CB944503) and the National Natural Science Foundation of China (81200470, 81000275, 31230047, 8110197). There are no conflicts of interest to declare.

Cited by 48 publications

References 54 publications

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling Pathway

Engineering the ovarian cycle using in vitro follicle culture

Short-term hypertonic exposure enhances in vitro follicle growth and meiotic competence of enclosed oocytes while modestly affecting mRNA expression of aquaporin and steroidogenic genes in the domestic cat model

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