Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3K/Akt/Foxo3a signalling pathway

Zhang, Xiaoli; Zhang, Haiyu; Gao, Qing; Ji, Shaolin; Hao, Jing

doi:10.1016/j.rbmo.2015.01.015

Cited by 15 publications

(9 citation statements)

References 23 publications

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“…Our results showed that quercetin could significantly reduce the p‐Akt/Akt, p‐PI3K/PI3K and p‐FoxO3a/FoxO3a protein ratios in rats with POF, suggesting that the protective effect of quercetin on CTX‐induced POF may be related to the PI3K/Akt/FoxO3a signalling pathway. Existing studies have also confirmed that the PI3K/Akt signalling pathway has stage specificity for follicular activation in oocytes, plays a decisive role in developing primordial follicles 49 and can regulate the development and growth of primordial follicles and the proliferation and differentiation of granulosa cells 50 . In addition, FoxO family members are the main effector proteins of the PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 89%

Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure

Zheng

Chen

et al. 2021

Basic Clin Pharma Tox

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To investigate the ability of quercetin to improve ovarian function and inhibit ovarian oxidative stress through the PI3K/Akt/FoxO3a signalling pathway in a rat model of premature ovarian failure (POF), we constructed a POF rat model with cyclophosphamide (CTX) and treated it with quercetin. Haematoxylin and eosin staining (H&E staining) was used to observe the morphological changes of the ovaries. The serum levels of AMH, E2, FSH, SOD, GSH‐Px and MDA were determined by enzyme‐linked immunosorbent assays. The expression of phosphatidylinositol 3‐kinase (PI3K), protein kinase B (Akt), forkhead box O3a (FoxO3a) and their phosphorylated forms AMH, FSH and their receptors in the ovary were detected by western blots. The mRNA expression of PI3K, Akt, FOXO3a, AMH, FSH and their receptors was detected by qRT‐PCR. Our results showed that quercetin could significantly increase the expression of AMH, E2, SOD and GSH‐Px, upregulate the protein expression of AMH, FSH and its receptor and decrease the expression ratio of phosphorylated PI3K, Akt, FOXO3a and the unphosphorylated forms. Moreover, quercetin inhibited the mRNA expression of PI3K, Akt and FOXO3a. These results suggest that quercetin can restore ovarian function and inhibit oxidative stress by regulating the PI3K/Akt/FoxO3a signalling pathway.

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Section: Discussionmentioning

confidence: 89%

Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure

Zheng

Chen

et al. 2021

Basic Clin Pharma Tox

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“…Activation of c-kit signaling plays an important role in the proliferation, differentiation, migration and apoptosis of many kinds of cells, such as melanocyte, mast cell, Cajal cell and hemopoietic stem cell [22, 23]. Previous studies have found the expression of c-kit receptor in oocytes from human and mouse, moreover, the signaling pathways downstream of c-kit play critical role in events like primordial follicle activation and follicular growth [24, 25]. Recently, Taniguchi et al have detected the expression of c-kit receptor in mouse embryo [26].…”

Section: Introductionmentioning

confidence: 99%

C-kit signaling promotes human pre-implantation 3PN embryonic development and blastocyst formation

Tan

Zou²,

Huang

et al. 2019

Reprod Biol Endocrinol

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Background Although in vitro culture system has been optimized in the past few decades, the problem of few or no high quality embryos has been still not completely solved. Accordingly, fully understanding the regulatory mechanism of pre-implantation embryonic development would be beneficial to further optimize the in vitro embryo culture system. Recent studies have found the expression of c-kit in mouse embryo and its promotion effects on mouse embryonic development. However, it is unclear the expression, the role and the related molecular regulatory mechanism of c-kit in human pre-implantation embryo development. Therefore, the present study is to determine whether c-kit is expressed in human pre-implantation embryos, and to investigate the possible regulatory mechanism of c-kit signaling in the process of embryonic development. Methods The present study includes human immature oocytes and three pronucleus (3PN) embryos collected from 768 women (28–32 ages) undergoing IVF, and normal 2PN embryos collected from ICR mice. Samples were distributed randomly into three different experimental groups: SCF group: G-1™ (medium for culture of embryos from the pro-nucleate stage to day 3) or G-2™ (medium for culture of embryos from day3 to blastocyst stage) + HSA (Human serum album) solution + rhSCF; SCF + imanitib (c-kit inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + imanitib; SCF + U0126 (MEK/ERK inhibitor) group: G-1™ or G-2™ + HSA solution + rhSCF + U0126; Control group: G-1™ or G-2™ + HSA solution + PBS; The rate of good quality embryos at day 3, blastulation at day 6 and good quality blastulation at day 6 were analysis. RT-PCR, western blot and immunofluorescence staining were applied to detect the target genes and proteins in samples collected from human or mice, respectively. Results c-kit was expressed ubiquitously in all human immature oocytes, 3PN embryos and 3PN blastocysts. In the experiment of human 3PN embryos, compared with other groups, SCF group showed obviously higher rate of good quality at day 3, better rate of blastocyst formation at day 6 and higher rate of good quality blastocyst formation at day 6. Furthermore, we observed a higher ETV5 expression in SCF group than that in other groups. Similar results were also found in animal experiment. Interestingly, we also found a higher phosphorylation level of MEK/ERK signal molecule in mice embryos from SCF group than those from other groups. Moreover, inhibition of MEK/ERK signaling would remarkably impeded the mice embryonic development, which might be due to the reduced ETV5 expression. Conclusions The present study firstly revealed that c-kit signaling might promote the human pre-implantation embryonic development and blastocyst formation by up-regulating the expression of ETV5 via MEK/ERK pathway. Our findings provide a new idea for optimizing the in vitro embryo culture condition during ART program, which is beneficial to obtain high quality embryos for infertile patients.

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“…In our previous study, the expression levels of Sohlh2 , Bmp4 , Bmp15 , and Gdf9 were also downregulated in Sohlh1 −/− mouse ovaries (data not reported). Both Sohlh2 and Bmp4 are also important factors that influence the PI3K pathway in mouse ovaries, leading to female infertility (Choi et al, ; Ding, Zhang, Mu, Li, & Hao, ; Y. Li, Zhang, Zhang, Sun, & Hao, ; X. Zhang et al, ). In addition, Bmp15 and Gdf9 can transduce signals from oocytes to granulosa cells (Elvin, Yan, Wang, Nishimori, & Matzuk, ; Paulini & Melo, ).…”

Section: Discussionmentioning

confidence: 99%

Primordial follicle activation is affected by the absence of Sohlh1 in mice

Liu

et al. 2018

Molecular Reproduction Devel

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Previous studies have reported that only primordial follicles and empty follicles can be found in 7.5 days postparturition (dpp) Sohlh1−/− mouse ovaries and females are infertility. There appears to be a defect in follicle development during the primordial‐to‐primary follicle transition in Sohlh1−/− mouse ovaries. However, detailed analyses of these phenomena have not been performed. In this study, we used Sohlh1−/− transgenic mice to explore the role of Sohlh1 in folliculogenesis. The results showed that only primordial follicles and empty follicles can be observed in Sohlh1−/− ovaries from 0.5 to 23.5 dpp. The expression of Foxo3 and FOXO3 was downregulated; nucleocytoplasmic shuttling of FOXO3 was normal in 7.5‐dpp Sohlh1+/+ but not Sohlh1−/− ovaries; and primordial follicle activation (PFA) was not observed in 7.5‐dpp Sohlh1−/− mice. The expression levels of KIT, AKT, and P308‐AKT were downregulated (p < 0.05), whereas that of P473‐AKT was not significantly changed (p > 0.05). The KIT/PI3K/AKT pathway was inhibited. Furthermore, we conducted a dual luciferase assay and chromatin immunoprecipitation. The results showed that SOHLH1 can upregulate the Kit gene by binding to the −3698 bp E‐box motif. The absence of Sohlh1 may affect PFA in mouse ovaries via downregulation of Kit and inhibition of the KIT/PI3K/AKT pathway.

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Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3K/Akt/Foxo3a signalling pathway

Cited by 15 publications

References 23 publications

Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure

Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide‐induced premature ovarian failure

C-kit signaling promotes human pre-implantation 3PN embryonic development and blastocyst formation

Primordial follicle activation is affected by the absence of Sohlh1 in mice

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