title: Endoplasmic reticulum stress is involved in granulosa cell apoptosis during follicular atresia in goat ovaries.
abstract: Follicular atresia is primarily induced by granulosa cell apoptosis, but description of the apoptotic pathway in granulosa cells is incomplete. In this study, we explored the possibility that endoplasmic reticulum (ER) stress could be involved in granulosa cell apoptosis during goat follicular atresia. Immunohistochemical analysis revealed that DNA damage-inducible transcript 3 (DDIT3) and glucose-regulated protein 78 (Grp78) were observed in scattered apoptotic granulosa cells of atretic follicles. Grp78 and DDIT3 mRNA and protein were upregulated in granulosa cells during follicular atresia, although DDIT3 was not significantly different between early atretic and progressed atretic follicles. Spontaneous apoptosis was also observed in vitro in granulosa cells induced by serum deprivation or by the ER stress agent tunicamycin, both inducing similar increases in DDIT3 mRNA. Activating transcription factor-6 (ATF6) and ATF4 mRNAs were significantly increased during granulosa cell apoptosis in vivo; in contrast to ATF6, ATF4 mRNA was attenuated after 16 hr of culture despite the persistence of ER stress. Taken together, ER stress-dependent DDIT3 pathways may play an important role in the regulation of selective granulosa cell apoptosis in goat ovaries during early follicular atresia. Serum deprivation could also increase apoptosis of cultured granulosa cells through the ER stress pathway as both ATF6 and PERK/eIF2α/ATF4 signaling have been implicated in the granulosa cell apoptosis of atretic follicles.
authors.affiliation: Key Laboratory of Animal Reproductive Endocrinology and Embryo Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Lin
authors.forename: YanZhou
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Fenglei
authors.initials: F
authors.lastname: Chen
authors.forename: ChenChen
authors.initials: C
authors.lastname: Cui
authors.forename: Linyong
authors.initials: L
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: YaPing
authors.initials: Y
authors.lastname: Jin
mesh_terms: D051696:Activating Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D005260:Female; D005496:Follicular Atresia / Q000502:physiology*; D006041:Goats / Q000502:physiology*; D006107:Granulosa Cells / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D051696:Activating Transcription Factors; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C018551:glucose-regulated proteins; D014415:Tunicamycin; D051742:Transcription Factor CHOP