Luman recruiting factor regulates endoplasmic reticulum stress in mouse ovarian granulosa cell apoptosis

Yang, Yanzhou; Lin, Peng; Chen, Fenglei; Wang, Aihua; Lan, Xiangli; Song, Yujie; Jin, Yaping

doi:10.1016/j.theriogenology.2012.11.017

Cited by 47 publications

(46 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…46 The mechanism of follicle atresia is the apoptosis of granulosa cells, and our previous study suggested that ERS is involved in follicle atresia and the apoptosis of granulosa cells. 32,33 The regression of the CL and the apoptosis of luteal cells might be regulated by ERS. Indeed, our results further suggested by previous data and which study revealed that the ERS-mediated apoptotic pathway might be involved in the bovine CL regression during estrous cycle.…”

Section: Discussionmentioning

confidence: 99%

“…33 The results suggested that the CHOP and caspase-12 proteins were all found in early apoptosis and late apoptosis. The CHOP and caspase-12 proteins were translocated from the cytoplasm into the nucleus during late apoptosis ( Figure 10).…”

Section: The Analysis Of Luteal Cell Apoptosismentioning

confidence: 95%

“…33 The complementary DNA was reverse transcribed using the PrimeScipt RT reagent kit (TaKaRa) according to the manufacturer's instructions.…”

Section: Real-time Polymerase Chain Reactionmentioning

confidence: 99%

“…The process of CLSM was performed according to a previous description. 33 Briefly, the luteal cells were cultured in the CLSM culture dishes and divided into 4 groups. After 24 hours of treatment, the luteal cells were immediately fixed in 4% paraformaldehyde for 20 minutes.…”

Section: Confocal Laser Scanning Microscopymentioning

confidence: 99%

See 3 more Smart Citations

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

Endoplasmic reticulum stress (ERS), which is a novel pathway of regulating cellular apoptosis and the function of ERS during corpus luteum (CL) regression, is explored. Early-luteal stage (day 2), mid-luteal stage (day 7), and late-luteal stage (day 14 and 20) were induced, and the apoptosis of luteal cells was detected by a terminal 2 0 -deoxyuridine 5 0 -triphosphate nick-end labeling (TUNEL) assay. The apoptotic cells were increased with the regression of CL, especially during the late-luteal stage. The ERS markers glucose-regulated protein 78 (Grp78), CCAAT/enhancer-binding protein homologous protein (CHOP), X-box binding protein 1 (XBP1), activating transcription factor 6a (ATF6a), eukaryotic initiation factor 2a (eIF2a), inositol-requiring protein 1a (IRE1a), caspase 12, and apoptosis marker caspase 3 were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry, in agreement with the results of the TUNEL assay; the expression levels of CHOP, caspase 12, and caspase 3 were increased during the process of CL regression. Luteal cells were isolated and cultured in vitro, and the apoptosis of luteal cells was induced by prostaglandin F2a. The ERS was attenuated by the ERS inhibitor tauroursodeoxycholic acid, and the apoptotic rate was analyzed by flow cytometry. The ERS markers Grp78, CHOP, XBP1s, ATF6a, eIF2a, IRE1a, caspase 12, and apoptotic execute marker caspase 3 were analyzed by real-time PCR and immunofluorescence, and the results suggested that the expression of CHOP, caspase 12, and caspase 3 were increased, and there was increased apoptosis of luteal cells. But the expression of IRE1a/XBP1s and eIF2a was not detected. Taken together, the ERS is involved in the CL regression of rats through the CHOP and caspase 12 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Analysis Of Luteal Cell Apoptosismentioning

confidence: 95%

“…33 The complementary DNA was reverse transcribed using the PrimeScipt RT reagent kit (TaKaRa) according to the manufacturer's instructions.…”

Section: Real-time Polymerase Chain Reactionmentioning

confidence: 99%

Section: Confocal Laser Scanning Microscopymentioning

confidence: 99%

See 2 more Smart Citations

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…27 Following prolonged ER stress, it is cleaved into active caspase-12 and activates downstream caspases, such as caspase-3 and caspase-9. [28][29][30] Endoplasmic reticulum stress and its associated genes are implicated in glucose and lipid metabolism, [31][32][33][34] pancreatic b-cell function, [35][36][37][38] insulin and leptin resistance, [39][40][41] liver disease, [42][43][44] atherosclerosis, and Alzheimer disease. 10,45,46 Emerging evidence also demonstrates that ER stress affects many aspects of follicle development and oocyte and embryo viability.…”

Section: Introductionmentioning

confidence: 99%

Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship

et al. 2016

View full text Add to dashboard Cite

Suboptimal cellular conditions result in the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and trigger ER stress. In this study, we investigated the effects of follicle stimulating hormone (FSH) on ER stress in granulosa cells (GCs) obtained from 3-week-old female C57BL6 mice 24 or 48 hours after intraperitoneal injection of 5 IU pregnant mare's serum gonadotropin (PMSG), and in primary mouse GCs in culture treated with FSH (10-100 mIU/mL) for 24 or 48 hours. Moreover, mouse GCs in culture were treated with tunicamycin (Tm) or thapsigargin (Tp), which induce ER stress by inhibiting N-glycosylation of ER proteins and ER calcium adenosine triphosphatase, respectively, and their response to FSH was evaluated. We found that FSH attenuated ER stress in mouse GCs in vivo and in vitro; messenger RNA levels of ER stress-associated genes Xbp1s, Atf6, Chop, and Casp12 were decreased upon exposure to FSH/PMSG. Activating transcription factor 4 protein levels also demonstrated consistent decrease following FSH stimulation. Both Tm and Tp treatments inhibited FSH response, ER stressinduced cells did not show any change in estradiol levels in response to FSH, whereas in untreated GCs, estradiol production increased 3-fold after incubation with FSH for 60 hours. Furthermore, ER stress-induced cells failed to demonstrate aromatase (Cyp19a1) expression upon exposure to FSH. Importantly, under high-ER stress conditions FSH stimulation was unable to downregulate the expression of ER stress-associated genes. Our findings suggest that FSH decreases ER stress in GCs under physiologic conditions. However, under conditions that cause a significant increase in ER stress, FSH response is attenuated.

show abstract

Effects of bisphenol A on ovarian follicular development and female germline stem cells

Zhu

Tian

et al. 2018

Arch Toxicol

View full text Add to dashboard Cite

Bisphenol A (BPA), one of the most frequently detected emerging pollutants in the environment, has been implicated in adverse effects in male and female reproduction at extremely low concentrations. This study aimed to investigate the effects and potential mechanism of BPA on mouse ovarian follicular development and female germline stem cells (FGSCs). Female CD-1 adult mice were administered gradient concentrations of BPA (12.5, 25, and 50 mg/kg/day) by intraperitoneal injection. We found that the number of atretic ovarian follicles was significantly increased at high BPA concentrations. Additionally, the numbers of primordial follicles, primary follicles, and corpus luteum (CL) were significantly reduced at high BPA concentrations. Interestingly, the number of FGSCs was remarkably reduced in BPA-treated ovaries. Furthermore, the increased apoptotic rate of FGSCs in vitro was triggered by BPA accompanied by increased BPA concentrations. To investigate the mechanism of BPA in ovarian follicular development, 193 differentially expressed proteins were identified in BPA-treated ovaries by the isobaric tags for relative and absolute quantification-coupled 2D liquid chromatography-mass spectrometry technique. A total of 106 proteins were downregulated and 85 proteins were upregulated. Among these proteins, the apoptosis-related protein SAFB-like transcriptional modulator (SLTM) was remarkably upregulated, and this result was consistent with western blotting. Taken together, our results suggest that an ovarian follicular development, especially, the development of primordial follicles, primary follicles, and the CL, is inhibited by high BPA concentrations, and the ovarian follicle atresia is initiated by BPA through upregulated expression of SLTM. Furthermore, BPA induces apoptosis of cultured FGSCs. The effect of BPA on ovarian follicular development and FGSCs, especially the effect on FGSCs, suggests a novel mechanism of how BPA causes female infertility.

show abstract

Luman recruiting factor regulates endoplasmic reticulum stress in mouse ovarian granulosa cell apoptosis

Cited by 47 publications

References 32 publications

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship

Effects of bisphenol A on ovarian follicular development and female germline stem cells

Contact Info

Product

Resources

About