LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

He, Meina; Zhang, Tuo; Zhu, Zijian; Qin, Shaogang; Wang, Huarong; Zhao, Lihua; Zhang, Xinran; Hu, Jiayi; Wen, Jing; Cai, Han; Xin, Qiliang; Guo, Qiang; Lin, Lin; Zhou, Bo; Zhang, Hua; Xia, Guoliang; Wang, Chao

doi:10.1111/acel.13102

Cited by 42 publications

(45 citation statements)

References 55 publications

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“…Blockade of autophagic flux and accumulation of nondegraded substrates in the form of autophagosome are linked to aging (12). Furthermore, apoptosis and autophagy are involved in the process of oocyte loss (13,14). Nlrp3 −/− female mice showed increased levels of ATG12, beclin 1, and LC3-II protein and reduced expression of p62/ SQSTM1 compared with an accumulation of LC3-I with p62-aged WT mice associated with an impairment of autophagy ( Fig.…”

Section: Age-related Autophagic and Apoptotic Changes In The Ovaries mentioning

confidence: 97%

Inhibition of the NLRP3 inflammasome prevents ovarian aging

et al. 2021

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Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.

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Section: Age-related Autophagic and Apoptotic Changes In The Ovaries mentioning

confidence: 97%

Inhibition of the NLRP3 inflammasome prevents ovarian aging

et al. 2021

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“…2A ). As autophagy is also reported to be active during follicular assembly and contributes to perinatal oocyte loss 5 , we, therefore, tested whether Xist could induce autophagy in perinatal mouse ovaries. As the microtubule-associated protein light chain 3B (LC3B) is a marker of autophagosomes, we observed more LC3B puncta presented in the cytoplasm of Xist- overexpressed oocytes (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It is well accepted that cellular apoptosis and autophagy processes are responsible for programmed oocyte loss occurring briefly around the time of birth 5 , 31 , 40 . Meanwhile, lncRNAs are emerging as central regulators in controlling cell autophagy or apoptosis in various diseases 49 , 50 .…”

Section: Discussionmentioning

confidence: 99%

“…However, multiple factors can induce excessive loss or overactivation of PFs in the PF pool, which is closely related to primary premature ovarian insufficiency (POI) and even to female infertility 3 , 4 . A better understanding of the regulatory mechanisms underlying PF pool formation will provide us with deep insights into the potential pathogenic mechanism of POI 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

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Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries

et al. 2021

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The fecundity of female mammals is resolved by the limited size of the primordial follicle (PF) pool formed perinatally. The establishment of PF pool is accompanied by a significant programmed oocyte death. Long non-coding RNAs (lncRNA) are central modulators in regulating cell apoptosis or autophagy in multiple diseases, however, the significance of lncRNAs governing perinatal oocyte loss remains unknown. Here we find that Yin-Yang 1 (YY1) directly binds to the lncRNA X-inactive-specific transcript (Xist) promoter and facilitates Xist expression in the perinatal mouse ovaries. Xist is highly expressed in fetal ovaries and sharply downregulated along with the establishment of PF pool after birth. Gain or loss of function analysis reveals that Xist accelerates oocyte autophagy, mainly through binding to pre-miR-23b or pre-miR-29a in the nucleus and preventing the export of pre-miR-23b/pre-miR-29a to the cytoplasm, thus resulting in decreased mature of miR-23b-3p/miR-29a-3p expression and upregulation miR-23b-3p/miR-29a-3p co-target, STX17, which is essential for timely control of the degree of oocyte death in prenatal mouse ovaries. Overall, these findings identify Xist as a key non-protein factor that can control the biogenesis of miR-23b-3p/miR-29a-3p, and this YY1-Xist-miR-23b-3p/miR-29a-3p-STX17 regulatory axis is responsible for perinatal oocyte loss through autophagy.

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“…Blockade of autophagic flux and accumulation of non-degraded substrates in the form of autophagosome are linked to aging (11). Furthermore, apoptosis and autophagy are involved in the process of oocyte loss (12,13). Interestingly, Nlrp3 -/female mice showed increased levels of ATG12, beclin 1 and LC3II protein, and reduced expression of p62/SQSTM1 ( Figure 3C).…”

Section: Age-related Autophagic and Apoptotic Changes In The Ovaries mentioning

confidence: 98%

Inhibition of the NLRP3 inflammasome prevents ovarian aging

Navarro‐Pando

Alcocer-Gómez

Castejón-Vega

et al. 2020

Preprint

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Inflammation is a hallmark of many processes during aging and reproductive physiology, negatively affecting female fertility. The goal of this study was to evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in female WT mice during reproductive aging. High expression of NLRP3, caspase 1 and IL-1β was also observed in granulosa cells from patients with primary ovarian insufficiency. Ablation of the NLRP3 inflammasome improved the survival and pregnancy rates in mice, increased hormonal levels of AMH, a biochemical marker of ovarian reserve, and autophagy rates in ovarian tissue. Deficiency of the NLRP3 inflammasome also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.

show abstract

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

Cited by 42 publications

References 55 publications

Inhibition of the NLRP3 inflammasome prevents ovarian aging

Inhibition of the NLRP3 inflammasome prevents ovarian aging

Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries

Inhibition of the NLRP3 inflammasome prevents ovarian aging

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