Hypoxia promotes luteal cell death in bovine corpus luteum.
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.
Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 1-1-1, Okayama, Japan.
Ryo
R
Nishimura
Junichi
J
Komiyama
Yukari
Y
Tasaki
Tomas J
TJ
Acosta
Kiyoshi
K
Okuda
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000378:metabolism / Q000502:physiology*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D008184:Luteal Cells / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011374:Progesterone; D053148:Caspase 3; D010100:Oxygen