Gonadal Expression of Foxo1, but Not Foxo3, Is Conserved in Diverse Mammalian Species1

Tarnawa, Edward D.; Baker, Michael D.; Aloisio, Gina M.; Carr, Bruce R.; Castrillón, Diego H.

doi:10.1095/biolreprod.112.105791

Cited by 53 publications

(24 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, the overlapped expression of foxo3a and foxo3b in the brain was also observed in zebrafish, which was suggested to be critical for the development of the nervous system (Peng et al 2010, Xie et al 2011, and is in line with neuronal roles of FOXO3 reported in mammals (Fukunaga et al 2005, Fukunaga & Shioda 2009, Polter et al 2009, Renault et al 2009). In mammals, FOXO3 protein was detected predominantly in the oocytes of primordial and primary follicles in the ovary of mouse (John et al 2008, Tarnawa et al 2013 and pig , which was implicated in suppressing the primordial oocyte activation (Castrillon et al 2003. Similarly, our present study also identified strong immuno reactive Foxo3a and Foxo3b signals in germ cells in the ovary of the orange-spotted grouper.…”

Section: Discussionsupporting

confidence: 78%

“…Given that the vitellogenic oocytes in teleosts are arrested at Prophase I of meiosis (Lubzens et al 2010), it could be hypothesized that the nuclear Foxo3a and Foxo3b in the vitellogenic oocytes of the orange-spotted grouper presumably contribute to the inhibition of Prophase I progression, which awaits further study. Mammalian FOXO3 proteins have been shown to be undetectable (John et al 2008, Tarnawa et al 2013 or barely detectable (Reddy et al 2005, Matsuda et al 2011 in the granulosa cells of healthy follicles. By contrast, prominent immunoreactive Foxo3a and Foxo3b signals were identified in follicular (presumably granulosa) cells surrounding the oocytes in the orange-spotted grouper.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides

Liu

Zhang

Shi

et al. 2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

FOXO3 has been shown to be a critical transcription factor for folliculogenesis in mammals, while the information on its roles in reproduction of nonmammalian vertebrates remains scarce. In this study, two foxo3 homologs, namely foxo3a and foxo3b, were identified in a teleost, the orange-spotted grouper Epinephelus coioides. foxo3a was mainly expressed in the central nervous system, ovary, and gut whereas foxo3b was expressed ubiquitously in tissues examined. In contrast to the dominant expression of mammalian FOXO3 in germ cells but barely detectable in ovarian follicular cells, immunoreactive Foxo3a and Foxo3b were identified both in the ovarian germ cells and follicular cells. The immunointensities of both Foxo3a and Foxo3b in ovarian follicular cells during vitellogenesis were significantly increased stage-dependently, and co-localized with Cyp19a1a. In the nucleus of ovarian follicular cells, both Foxo3a and Foxo3b immunostaining could be detected at the vitellogenic stages. Transient transfection and EMSA showed that Foxo3a and Foxo3b upregulated cyp19a1a promoter activities in vitro through a conserved Foxo-binding site, with the latter being a more potent activator. However, ChIP analysis showed that only Foxo3b binds to cyp19a1a proximal promoter region containing the conserved Foxo-binding site in the vitellogenic ovary. Taken together, these results suggested that Foxo3a and Foxo3b are involved in the ovarian development possibly through regulating the ovarian germ cells as well as follicular cells, and Foxo3b but not Foxo3a may activate cyp19a1a in the ovarian follicular cells during vitellogenesis in the orange-spotted grouper.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides

Liu

Zhang

Shi

et al. 2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…7 A). Foxo1 expression was used as a convenient marker of undifferentiated spermatogonia (Goertz et al 2011, Tarnawa et al 2013). Immunostaining and counts revealed normal numbers of undifferentiated spermatogonia in Vasa-Cre; Rheb f /− testes at all time points (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Foxo1 is specifically expressed in undifferentiated spermatogonia, and the three Foxos together regulate multiple steps of spermatogenesis including stem cell maintenance and differentiation (Goertz et al 2011, Tarnawa et al 2013). Pten is also required for spermatogenesis; its inactivation with the germline-specific Vasa-Cre (Gallardo et al 2007a) results in severe defects in spermatogonial maintenance and differentiation, at least in part through Foxo1 (Goertz et al 2011).…”

Section: Introductionmentioning

confidence: 99%

The small GTPase Rheb is required for spermatogenesis but not oogenesis

Baker¹,

Ezzati²,

Aloisio³

et al. 2014

Reproduction

View full text Add to dashboard Cite

The process of germ cell development is under the tight control of various signaling pathways among which the PI3K-Akt-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study we aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little is known about its role in the germline. We have exploited genetic approaches in the mouse to study the role of Rheb in the germline and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germline resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally-redundant factors that can compensate for Rheb deficiency within oocytes.

show abstract

“…Notably, several studies reported how the various components of this pathway have sex-specific roles. Foxo1 is specifically expressed in undifferentiated spermatogonia, and the three Foxos together regulate multiple steps of spermatogenesis comprising stem cell maintenance and differentiation (Figure 3) (Goertz et al , 2011; Tarnawa et al , 2013). Pten is also required for spermatogenesis and its inactivation with the germ line-specific Vasa-Cre (Tg(Ddx4-cre)1Dcas) (Gallardo et al , 2007) results in severe defects in spermatogonial maintenance and differentiation, in part through Foxo1 (Goertz et al , 2011).…”

Section: Mtor and Testicular Cellsmentioning

confidence: 99%

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Jesus

Oliveira

Sousa

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

show abstract

Gonadal Expression of Foxo1, but Not Foxo3, Is Conserved in Diverse Mammalian Species1

Cited by 53 publications

References 53 publications

Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides

Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides

The small GTPase Rheb is required for spermatogenesis but not oogenesis

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Contact Info

Product

Resources

About