The role of autophagy in follicular development and atresia in rat granulosa cells

Choi, Jaehoon; Jo, Min Wha; Lee, Eun Young; Yoon, Byung Koo; Choi, Doo Seok

doi:10.1016/j.fertnstert.2009.11.021

Cited by 146 publications

(129 citation statements)

References 45 publications

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“…However, some studies have reported that nonapoptotic forms of PCD such as autophagy can be induced in human granulosa cells (Duerrschmidt et al 2006, Serke et al 2009, Vilser et al 2010. We recently reported that autophagy is induced mainly in the granulosa cells and promotes apoptotic cell death (Choi et al 2010(Choi et al , 2011a. These results suggest that autophagy is directly involved in follicular atresia and plays an important role in the regulation of apoptotic granulosa cell death during folliculogenesis.…”

Section: Introductionmentioning

confidence: 83%

“…Granulosa cell autophagy has been recognized as the cellular mechanism responsible for follicular atresia by affecting apoptotic cell death (Choi et al 2010(Choi et al , 2011a. However, the role of the PI3K/AKT pathway and mTOR in the regulation of granulosa cell autophagy has remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In granulosa cells, gonadotropin treatment activates the PI3K/AKT pathway, which also increases mTOR activity (Alam et al 2004, Hunzicker-Dunn et al 2012. The PI3K/AKT pathway may therefore also be involved in the regulation of granulosa cell autophagy via control of mTOR activity during follicular development and atresia, as gonadotropin is known to suppress granulosa cell autophagy in follicular development (Choi et al 2010). However, there is also a report suggesting that mTOR activation by gonadotropin may not be controlled by the PI3K/AKT pathway in rat granulosa cells (Kayampilly & Menon 2007), and there is no direct evidence of the involvement of the PI3K/AKT pathway through mTOR in granulosa cell autophagy regulation.…”

Section: Introductionmentioning

confidence: 99%

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AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia

Choi

Lee

et al. 2014

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In this study, we examined whether granulosa cell autophagy during follicular development and atresia was regulated by the class I phosphoinositide-3 kinase/protein kinase B (AKT) pathway, which is known to control the activity of mammalian target of rapamycin (mTOR), a major negative regulator of autophagy. Ovaries and granulosa cells were obtained using an established gonadotropin-primed immature rat model that induces follicular development and atresia. Autophagy was evaluated by measuring the expression level of microtubule-associated protein light chain 3-II (LC3-II) using western blots and immunohistochemistry. The activity of AKT and mTOR was also examined by observing the phosphorylation of AKT and ribosomal protein S6 kinase (S6K) respectively. After gonadotropin injection, LC3-II expression was suppressed and phosphorylation of AKT and S6K increased in rat granulosa cells. By contrast, gonadotropin withdrawal by metabolic clearance promoted LC3-II expression and decreased phosphorylation of AKT and S6K. In addition, in-vitro FSH treatment of rat granulosa cells also indicated inhibition of LC3-II expression accompanied by a marked increase in phosphorylation of AKT and S6K. Inhibition of AKT phosphorylation using AKT inhibitor VIII suppressed FSH-mediated phosphorylation of S6K, followed by an increase in LC3-II expression. Furthermore, co-treatment with FSH and AKT inhibitor increased the levels of apoptosis and cell death of granulosa cells compared with the single treatment with FSH. Taken together, our findings indicated that AKT-mediated activation of mTOR suppresses granulosa cell autophagy during follicular development and is involved in the regulation of apoptotic cell death.

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Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia

Choi

Lee

et al. 2014

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“…In testis, follicle-stimulating hormone (FSH) in all cycles is to increase spermatogonia and subsequent spermatocyte numbers, which is similar to the physiological role of FSH on granulosal cells. Previous studies had demonstrated that FSH functions as an autophagy inhibitor in ovarian granulosal cells [26]. We hypothesis that FSH might also contribute to the inhibition of autophagy in testicular diploid germ cells, while detailed molecular pathways in diploid germ cells still remain to be documented.…”

Section: Autophagy In Diploid Germ Cellsmentioning

confidence: 88%

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

Tang¹,

Wang²

2017

Testes and Ovaries - Functional and Clinical Differences and Similarities

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Mammalian spermatogenesis is a high regulated biological process occurring in the seminiferous tubules in the testis. The processing of this program requires delicate balance between cell proliferation, differentiation, apoptosis, and expedite cell interaction.Autophagy, an evolutionarily conserved cell reprograming machinery, had been shown to function as an important regulatory mechanism in spermatogenesis and steroid production in testis. Herein, we mainly focused on our understanding of autophagy in mammalian testis. By showing autophagy in physiological and pathophysiological conditions, we try to elicit the regulatory role of autophagy in spermatogenic cells and somatic cells of testis. Moreover, this review is intended to point out factors and mechanisms, which contribute to the initiation of autophagy in testicular cells.

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“…Staining was not observed in the oocyte proper or theca cells in any stage follicle [62]. In mice, expression studies also indicate a role for autophagy during folliculogenesis.…”

Section: Reproductive Infertilitymentioning

confidence: 89%

Altering Autophagy: Mouse Models of Human Disease

Hale¹,

Ledbetter²,

Gawriluk³

2013

Autophagy - A Double-Edged Sword - Cell Survival or Death?

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The role of autophagy in follicular development and atresia in rat granulosa cells

Cited by 146 publications

References 45 publications

AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia

AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

Altering Autophagy: Mouse Models of Human Disease

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