title: 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'-deoxyuridine 5'-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 6α (ATF6α), eukaryotic initiation factor 2α (eIF2α), inositol-requiring protein 1α (IRE1α), 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 F2α. 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, ATF6α, eIF2α, IRE1α, 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 IRE1α/XBP1s and eIF2α was not detected. Taken together, the ERS is involved in the CL regression of rats through the CHOP and caspase 12 pathway.
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China nxykdyang@163.com 4083304@163.com peixuiying@163.com.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Histology and Embryology, Ningxia Medical University, Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Yinchuan, P.R. China nxykdyang@163.com 4083304@163.com peixuiying@163.com.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008184:Luteal Cells / Q000378:metabolism / Q000473:pathology; D008183:Luteal Phase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003341:Luteolysis / Q000187:drug effects; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011555:Pseudopregnancy; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D051702:Activating Transcription Factor 6; C497113:Atf6 protein, rat; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C575026:Ern1 protein, rat; D015852:Eukaryotic Initiation Factor-2; C051684:GRP78 protein, rat; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D009097:Multienzyme Complexes; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C000605545:Xbp1 protein, rat; D051742:Transcription Factor CHOP; D015237:Dinoprost; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat; D053454:Caspase 12; D053148:Caspase 3
keywords: apoptosis; corpus luteum regression; endoplasmic reticulum stress; rats