Hypoxia promotes luteal cell death in bovine corpus luteum
Hypoxia promotes luteal cell death in bovine corpus luteum
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DOI：
10.1095/biolreprod.107.063370
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Okuda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Nishimura, Ryo;Komiyama, Junichi;Okuda, Kiyoshi
众所周知，血液供应减少导致的低氧会诱导细胞的各种反应，包括细胞凋亡。本研究旨在探讨低氧条件(低氧)是否诱导黄体细胞凋亡。低氧(3%O-2)培养的牛黄体细胞在培养24和48 h的细胞死亡率显著高于常氧(20%O-2)培养的细胞，而孕酮(M)水平从8 h开始显著降低。低氧培养48 h的牛黄体细胞出现细胞核缩小和DNA片段化等特征，低氧使培养24和48 h的BNIP3和caspase 3的mRNA表达增加。低氧对bcl2和Bax基因的表达无明显影响。低氧还可使BNIP3蛋白表达增加，并激活CAPase-3。P4治疗可减轻缺氧条件下细胞死亡、caspase-3mRNA表达和caspase-3活性。本研究的总体结果表明，低氧通过促进促凋亡蛋白BNIP3的表达和激活caspase-3来诱导黄体细胞的凋亡，低氧诱导黄体细胞凋亡的部分原因是P4的产生减少。由于低氧抑制了牛黄体细胞P4的合成，我们认为黄体供血减少引起的缺氧是导致功能性和结构性黄体溶解的主要因素之一。
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 bad significantly lower progesterone (M) 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 capsase-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.