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Hypoxia promotes luteal cell death in bovine corpus luteum.

Abstract
Low oxygen caused by a decreasing blood supply is known to induce various responses of cells, including apoptosis. The present study was conducted to examine whether low-oxygen conditions (hypoxia) induce luteal cell apoptosis in cattle. Bovine midluteal cells incubated under hypoxia (3% O(2)) showed significantly more cell death than did those incubated under normoxia (20% O(2)) at 24 and 48 h of culture, and had significantly lower progesterone (P4) levels starting at 8 h. Characteristic features of apoptosis, such as shrunken nuclei and DNA fragmentation, were observed in cells cultured under hypoxia for 48 h. Hypoxia increased the mRNA expressions of BNIP3 and caspase 3 at 24 and 48 h of culture. Hypoxia had no significant effect on the expressions of BCL2 and BAX mRNA. Hypoxia also increased BNIP3 protein, and activated caspase-3. Treatment of P4 attenuated cell death, caspase-3 mRNA expression, and caspase-3 activity under hypoxia. Overall results of the present study indicate that hypoxia induces luteal cell apoptosis by enhancing the expression of proapoptotic protein, BNIP3, and by activating caspase-3, and that the induction of apoptosis by hypoxia is partially caused by a decrease in P4 production. Because hypoxia suppresses P4 synthesis in bovine luteal cells, we suggest that oxygen deficiency caused by a decreasing blood supply in bovine corpus luteum is one of the major factors contributing to both functional and structural luteolysis.
AuthorsRyo Nishimura, Junichi Komiyama, Yukari Tasaki, Tomas J Acosta, Kiyoshi Okuda
JournalBiology of reproduction (Biol Reprod) Vol. 78 Issue 3 Pg. 529-36 (Mar 2008) ISSN: 0006-3363 [Print] United States
PMID18046014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Progesterone
  • Caspase 3
  • Oxygen
Topics
  • Animals
  • Apoptosis (drug effects, genetics)
  • Caspase 3 (genetics, metabolism)
  • Cattle
  • Cell Death
  • Cell Hypoxia (physiology)
  • Cells, Cultured
  • Corpus Luteum (metabolism, physiology)
  • DNA Fragmentation (drug effects)
  • Female
  • Luteal Cells (metabolism, physiology)
  • Models, Biological
  • Oxygen (pharmacology)
  • Progesterone (metabolism)
  • Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Time Factors

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