Sun Fengyun, Betzendahl Ilse, Van Wemmel Kelly, Cortvrindt Rita, Smitz Johan, Pacchierotti Francesca, Eichenlaub-Ritter Ursula
Genetechnology/Microbiology, Faculty of Biology, University of Bielefeld, Bielefeld, Germany.
Mutat Res. 2008 Mar 12;651(1-2):114-24. doi: 10.1016/j.mrgentox.2007.10.008. Epub 2007 Nov 4.
Trichlorfon (TCF), an organophosphate insecticide and potent inhibitor of choline esterases, was previously shown to induce first meiotic nondisjunction and spindle aberrations in isolated, follicle cell-denuded mouse oocytes maturing in vitro. To explore dose-response and direct and indirect, potentially synergistic effects of TCF on the somatic cells and the oocyte within a follicle, we presently employed preantral follicle culture. 100 microg/ml TCF added at the time of hormonally stimulated resumption of meiosis of follicle cell-enclosed mouse oocytes, 16 h before in vitro ovulation, induced significant rises in first meiotic nondisjunction in oocytes from preantral follicle culture. Lower concentrations (6 microg/ml TCF) disturbed polar body formation. Nuclear maturation to meiosis II in absence of cytokinesis resulted in significant increases in polyploidy. Oocytes maturing in follicles in the presence of TCF had aberrant second meiotic spindles. Influences of TCF on somatic cell function were evident by reduced follicular mucification in vitro and deceased progesterone production. In contrast to TCF, acetylcholine (0.1-100 microM) increased progesterone production. The observations therefore suggest that TCF influences oocyte maturation and folliculogenesis directly and indirectly. High TCF is aneugenic at first meiotic division in oocytes, irrespective of the presence or absence of follicle cells. At lower concentrations TCF interferes with spindle formation, chromosome congression at meiosis II, and coordination of nuclear and cytoplasmic maturation, posing risks for second meiotic errors. The observations suggest that chronic TCF exposure during maturation in the follicle may predispose oocytes to the formation of chromosomally unbalanced preimplantation embryos after fertilization.
敌百虫（TCF）是一种有机磷杀虫剂，也是胆碱酯酶的强效抑制剂，此前已证明它能在体外成熟的、去除卵泡细胞的分离小鼠卵母细胞中诱导第一次减数分裂不分离和纺锤体畸变。为了探究TCF对卵泡内体细胞和卵母细胞的剂量反应以及直接和间接的潜在协同作用，我们目前采用了腔前卵泡培养法。在激素刺激卵泡细胞包裹的小鼠卵母细胞恢复减数分裂时（体外排卵前16小时）添加100微克/毫升的TCF，可诱导腔前卵泡培养的卵母细胞中第一次减数分裂不分离显著增加。较低浓度（6微克/毫升TCF）会干扰极体形成。在没有胞质分裂的情况下核成熟至减数分裂II会导致多倍体显著增加。在TCF存在下于卵泡中成熟的卵母细胞具有异常的第二次减数分裂纺锤体。TCF对体细胞功能的影响通过体外卵泡黏液形成减少和孕酮分泌减少得以体现。与TCF相反，乙酰胆碱（0.1 - 100微摩尔）可增加孕酮分泌。因此，这些观察结果表明TCF直接和间接地影响卵母细胞成熟和卵泡发生。高浓度的TCF在卵母细胞的第一次减数分裂时具有致染色体不分离作用，无论卵泡细胞是否存在。在较低浓度下，TCF会干扰纺锤体形成、减数分裂II时染色体向赤道板的汇聚以及核与胞质成熟的协调，从而增加第二次减数分裂出错的风险。这些观察结果表明，卵泡成熟过程中慢性暴露于TCF可能使卵母细胞在受精后易于形成染色体不平衡的植入前胚胎。
