Specificity of the requirement for Foxo3 in primordial follicle activation

John, George B.; Shirley, Lane; Gallardo, Teresa; Castrillón, Diego H.

doi:10.1530/rep-06-0051

Cited by 86 publications

(82 citation statements)

References 57 publications

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“…Further, inhibition of AKT in neonatal rat ovary organ culture resulted in decreased CDK1/p27 expression and decreased phosphorylated FOXO3a and was associated with reduced oocyte apoptosis (Liu et al 2009). It is not, however, likely that FOXO3a is involved in cyst breakdown as FOXO3a knockouts demonstrate normal primordial follicle formation (John et al 2007). However, CDK1/p27 knockout mice show accelerated primordial follicle formation and CDK1/p27 is expressed in somatic cells surrounding cysts (Rajareddy et al 2007).…”

Section: Growth Factors and Signaling Moleculesmentioning

confidence: 99%

Follicular assembly: mechanisms of action

Pepling¹

2012

Reproduction

208

190

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The differentiation of primordial germ cells (PGCs) into functional oocytes is important for the continuation of species. In mammals, PGCs begin to differentiate into oocytes during embryonic development. Oocytes develop in clusters called germ line cysts. During fetal or neonatal development, germ cell cysts break apart into single oocytes that become surrounded by pregranulosa cells to form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst undergoes cell death with only one-third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control cyst breakdown, oocyte survival, and follicle assembly are currently under investigation. This review describes the mechanisms that have been implicated in the control of primordial follicle formation, which include programmed cell death regulation, growth factor and other signaling pathways, regulation by transcription factors and hormones, meiotic progression, and changes in cell adhesion. Elucidation of mechanisms leading to formation of the primordial follicle pool will help research efforts in ovarian biology and improve treatments of female infertility, premature ovarian failure, and reproductive cancers.

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Section: Growth Factors and Signaling Moleculesmentioning

confidence: 99%

Follicular assembly: mechanisms of action

Pepling¹

2012

Reproduction

208

190

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“…PF assembly is normal in female mice bearing a null Foxo3 mutation ( John et al 2007). Immediately thereafter, however, PFs undergo global activation and grow in an essentially synchronized manner, resulting in ovarian hyperplasia by PND14.…”

mentioning

confidence: 99%

Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse

et al. 2007

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Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n ¼ 348, $1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility.

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“…John et al (12) reported that as the downstream of PI3K/Akt, hyperphosphorylation of FoxO3a induced over-activation of primordial follicules (8,26,28). As previous studies have systematically reported that maintaining optimal activities of PI3K/Akt signaling pathway is essential for normal ovarian function, which not only regulates the balance between survival and activation of primordial follicles, but also is vital for the proliferation and differentiation of GCs (26)(27)(28).…”

Section: Discussionmentioning

confidence: 96%

“…Previous investigations have indicated that FoxO3a is highly expressed and localized to the nucleus during the dormancy of primordial follicles, then is phosphorylated and exported to the cytoplasm during follicular activation in mice (10). However, the activity of FoxO3a is suppressed in later-growing follicles, indicating that the downregulation of FoxO3a in oocytes may be a prerequisite for the initiation of oocyte growth during follicular activation (11,12).…”

Section: Introductionmentioning

confidence: 99%

Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary

Zhang

Liao

et al. 2016

Molecular Medicine Reports

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Abstract. Obesity has a negative effect on ovarian functions, which is reported to increase the risk of infertility. The mechanism underlying obesity-induced infertility is not yet clear. The present study established a high-fat diet (HFD)-induced obesity mouse model to elucidate the mechanisms underlying the effect of HFD-induced obesity on follicular development in the mouse ovary. The 4-week-old female mice were fed with HFD or normal control (NC) diet for 15 or 20 weeks. Body mass index was used to demonstrate that the mice were obese following HFD treatment. The follicular development of the ovaries from the HFD group mice was retarded in a time-dependent manner, as demonstrated by morphological and histological examination of the ovaries. Further investigation via western blot analysis demonstrated that the activity of the transcription factor, forkhead box O3a (FoxO3a), was increased by HFD through downregulated FoxO3a phosphorylation, which may contribute to the inhibited development of ovarian follicles. To determine the regulatory mechanism of FoxO3 on the follicular development, the expression levels of FoxO3a target protein, Smad1/5/8, were also determined and there was significant decrease in phosphorylated Smad1/5/8 in the ovaries from the HFD group compared with the NC group, indicating that FoxO3a/Smad1/5/8 may be important in the regulation of follicular development. The expression levels of the upstream regulator of FoxO3a, Akt, were also examined and it was demonstrated that Akt phosphorylation was significantly reduced in the HFD group compared with the NC group, indicating that Akt/FoxO3a may be also involved in follicular development. Together, the experiments demonstrated that HFD-induced obesity affected the activity of the Akt/FoxO3a/Smad1/5/8 signaling pathway in a time-dependent manner during the follicular development of the mouse ovary, leading to abnormal follicular development. These findings may provide part of a theoretical basis for the clinical prevention and treatment of obesity-associated female infertility.

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Specificity of the requirement for Foxo3 in primordial follicle activation

Cited by 86 publications

References 57 publications

Follicular assembly: mechanisms of action

Follicular assembly: mechanisms of action

Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse

Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary

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