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.
Nishimura
Ryo
R
Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 1-1-1, Okayama, Japan.
Komiyama
Junichi
J
Tasaki
Yukari
Y
Acosta
Tomas J
TJ
Okuda
Kiyoshi
K
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