Maturation and fertilization of nonhuman primate oocytes are compromised by oral administration of a cyclooxygenase-2 inhibitor

口服环氧合酶-2抑制剂会损害非人灵长类动物卵母细胞的成熟和受精。

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Abstract

OBJECTIVE: To determine if oral administration of a cyclooxygenase-2 (COX2) inhibitor affects oocyte nuclear maturation and fertilization in nonhuman primates. DESIGN: Laboratory research study. SETTING: Medical school. ANIMAL(S): Adult female cynomolgus monkeys (Macaca fascicularis). INTERVENTION(S): Monkeys received gonadotropins to stimulate multiple follicular development. An ovulatory dose of hCG was administered either alone or with oral celecoxib, a COX2 inhibitor. Oocytes were retrieved 36 hours later and exposed to sperm in vitro. MAIN OUTCOME MEASURE(S): Oocytes were assessed for nuclear status at retrieval, resumption of meiosis in vitro, and success of in vitro fertilization. RESULT(S): Treatment with hCG alone yielded oocytes that were primarily (72.9%) at the meiosis II (MII) stage of nuclear maturation; few oocytes were obtained at the germinal vesicle and germinal vesicle breakdown stages. Treatment with hCG and celecoxib yielded fewer mature (MII) oocytes (35.6%) and more oocytes at less mature stages compared with oocytes from monkeys treated with hCG alone. The majority (68.3 ± 15.9%) of MII oocytes from monkeys treated with hCG alone fertilized in vitro, compared with only 11.0 ± 5.9% of MII oocytes from monkeys treated with hCG and celecoxib. CONCLUSION(S): Oral administration of a COX2 inhibitor reduced the rate of oocyte nuclear maturation and the success of in vitro fertilization. Drugs of this class may block multiple essential steps in female reproduction and be effective contraceptives for women.

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