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.