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

Abstract

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.

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

“…Previous studies have demonstrated that the ER is involved in the cell death minimal conversion of LC3 I/II and increased expression of P62 [40]. GRP78, CHOP, XBP1s, and eIF2α are the ERS markers that are often analyzed to investigate the mechanism of the ER stress-mediated apoptotic pathway [41]. The up-regulation of GRP78 is involved in autophagy activation, and the phosphorylation of eIF2α is essential for autophagy.…”

Establishment and validation of an endoplasmic reticulum stress reporter to monitor zebrafish ATF6 activity in development and disease

“…Recently, ATF6 has been implicated in the development of multiple tissue types, and dysregulation of ATF6 expression is related to disease (Hillary and FitzGerald, 2018). Developmental roles of ATF6 include mesoderm differentiation (Kroeger et al, 2018), osteogenesis and chondrogenesis (Guo et al, 2016;Jang et al, 2012;Kim et al, 2014;Maeda et al, 2015;Xiong et al, 2015), neurodevelopment (Cho et al, 2009;Naughton et al, 2015;Saito et al, 2012;Zhang et al, 2007), adipogenesis and lipogenesis (Lowe et al, 2012), and formation of female reproductive structures (Lin et al, 2012;Park et al, 2013;Xiong et al, 2016;Yang et al, 2015). Most relevant to our work is the role of ATF6 in ocular and muscular embryology, because these tissues had the highest ATF6 reporter expression during zebrafish development.…”

Herp depletion arrests the S phase of the cell cycle and increases estradiol synthesis in mouse granulosa cells

“…The pituitary surge of LH/FSH has been thoroughly demonstrated to initiate a complex series of cellular and molecular events in periovulatory follicles leading to the resumption of oocyte meiosis, breakdown of the follicle wall and oocyte release, followed by the subsequent luteinization of the postovulatory follicle [ 2 ]. As found in numerous studies, not only endocrine but also paracrine and autocrine factors, which include gonadal steroids, growth factors, cytokines and intracellular proteins, play important roles in ovarian follicular development [ 3 ]; for example, an increasing body of evidence indicates that members of the mammalian endoplasmic reticulum (ER) stress response-related molecular chaperones regulate key genes that are crucial for follicular development, atresia and luteinization [ 4 , 5 , 6 , 7 ]. To date, the exact molecular mechanisms and interactions between the ER stress response and follicular development remain unclear.…”