Document Detail

Alterations of Circadian Clockworks During Differentiation and Apoptosis of Rat Ovarian Cells.
MedLine Citation:
PMID:  21797776     Owner:  NLM     Status:  Publisher    
Ovarian development is related to cell proliferation, differentiation, and apoptosis of granulosa cells and luteal cells under the control of various modulators, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and growth factors. In the present study, the expression of clock genes and the related regulation mechanism were analyzed in different ovarian cell types during differentiation and apoptosis. The authors focused on the circadian expression of Per2 as a core clock gene for the maintenance of circadian rhythms. By using a real-time monitoring system of the Per2 promoter activity, the circadian oscillation was analyzed in the granulosa and luteal cells from preantral follicles, antral follicles, and corpora lutea of immature Per2 promoter-destabilized luciferase transgenic rats that were primed with diethylstilbestrol, equine chorionic gonadotropin (eCG), and/or human CG. In addition, transcript levels of Per2, Bmal1, Clock, and Nampt were quantified by quantitative polymerase chain reaction (qPCR). Immunohistochemical studies revealed strong circadian rhythmicity of PER2 protein in the luteal cells, but apparently little rhythmicity in granulosa cells of both preantral and antral follicles. In vitro monitoring of promoter activity showed generation of several oscillations in luteal cells after exposure to dexamethasone (DXM), whereas oscillatory amplitudes of immature and mature granulosa cells were rapidly attenuating. The circadian rhythm of the Bmal1 transcript levels, but not the Per2 transcript, was very weak in the granulosa cells, as compared with that in luteal cells. Granulosa cells gained a strong circadian rhythm ability of the Per2 promoter activity after stimulation with FSH for 3 days. In contrast, LH had little effect on the circadian rhythm before stimulation of granulosa cells with FSH, probably owing to lack of LH receptor. In luteal cells, induction of apoptosis by inhibiting progesterone synthesis resulted in deregulation of Per2 circadian oscillation. Transcript levels of Bmal1 and Clock, but not Per2 and Nampt, were significantly decreased in apoptotic luteal cells. The Bmal1 transcript level was particularly reduced. Consequently, these results strongly suggest the circadian clockwork alters in ovarian cells during follicular development, luteinization, and apoptosis, and expression of Bmal1 may be related to the switch-on and switch-off of the circadian oscillation. (Author correspondence: ).
Guiyan Chu; Kaoru Yoshida; Sayoko Narahara; Miho Uchikawa; Madoka Kawamura; Nobuhiko Yamauchi; Yongmei Xi; Yasufumi Shigeyoshi; Seiichi Hashimoto; Masa-Aki Hattori
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Publication Detail:
Journal Detail:
Title:  Chronobiology international     Volume:  28     ISSN:  1525-6073     ISO Abbreviation:  -     Publication Date:    2011 Jul.
Date Detail:
Created Date:  2011-7-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501362     Medline TA:  Chronobiol Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  477-487     Citation Subset:  -    
Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture , Kyushu University , Fukuoka , Japan.
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