Reese J, Zhao X, Ma W G, Brown N, Maziasz T J, Dey S K
Department of Pediatrics, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City, Kansas 66160-7338, USA.
Endocrinology. 2001 Jul;142(7):3198-206. doi: 10.1210/endo.142.7.8307.
Cyclooxygenase (COX)-derived prostaglandins are critical in female reproduction. Gene targeting studies show that ovulation, fertilization, implantation, and decidualization are defective in COX-2 deficient mice. We used genetic and pharmacologic approaches to perturb COX function and examine the differential and synergistic effects of inhibition of COX-1, COX-2, or of both isoforms on reproductive outcomes during early pregnancy in mice. The results demonstrate that simultaneous inhibition of COX-1 and COX-2 produces more severe effects on early pregnancy events than inhibition of either isoform alone. The effects of pharmacological inhibition of COX-2 on female reproductive functions were less severe than the null mutation of the COX-2 gene. A combined approach showed that COX-2 inhibition in COX-1(-/-) mice induced complete reproductive failure, suggesting a lack of alternative sources of prostaglandin synthesis. This investigation raises caution regarding the indiscriminate use of COX inhibitors and shows for the first time the distinct and overlapping pathways of the cyclooxygenase systems in female reproduction.
环氧化酶（COX）衍生的前列腺素在雌性生殖中至关重要。基因靶向研究表明，COX - 2缺陷小鼠的排卵、受精、着床和蜕膜化均存在缺陷。我们采用遗传学和药理学方法干扰COX功能，研究抑制COX - 1、COX - 2或两种亚型对小鼠早期妊娠生殖结局的差异和协同作用。结果表明，与单独抑制任一亚型相比，同时抑制COX - 1和COX - 2对早期妊娠事件的影响更为严重。COX - 2的药理学抑制对雌性生殖功能的影响不如COX - 2基因无效突变严重。联合研究表明，在COX - 1（- / -）小鼠中抑制COX - 2会导致完全生殖失败，这表明缺乏前列腺素合成的替代来源。这项研究对不加区分地使用COX抑制剂提出了警示，并首次揭示了环氧化酶系统在雌性生殖中独特且重叠的途径。
