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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Effects of 4-hydroxyandrostenedione and hyperstimulation with pregnant mare serum gonadotrophin on early embryonic development in rats.
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Effects of 4-hydroxyandrostenedione and hyperstimulation with pregnant mare serum gonadotrophin on early embryonic development in rats.

机译：4-羟基雄烯二酮和母马血清促性腺激素的过度刺激对大鼠早期胚胎发育的影响。

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摘要

A possible role of high oestradiol levels in mediating the adverse effects of hyperstimulation with pregnant mare serum gonadotrophin (PMSG) on early embryonic development in the rat was investigated using an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), to inhibit endogenous oestradiol production. Three experiments were conducted in this study. In the first, varying doses of 4-OHA were administered either concurrently with human chorionic gonadotropin (hCG) to pro-oestrus female rats hyperstimulated at early di-oestrus stage with 20 IU PMSG or alone into nonhyperstimulated pro-oestrus females. At high doses of 1000, 2000, or 5000 microg/rat, 4-OHA substantially improved the survival of embryos in hyperstimulated females, while low doses of 100 and 500 microg/rat were ineffective. The protective effect of 4-OHA on embryo count was optimum at 2000 microg. When administered alone, only the highest dose of 5000 microg/rat 4-OHA increased embryo count. In the second experiment, higher doses of PMSG were studied (30 or 40 IU), with or without 5000 microg/rat 4-OHA given at the time of hCG injection. PMSG proved to be more detrimental with increasing dose, and 5000 microg/rat 4-OHA was able to rescue embryos from death in the 30, but not 40, PMSG group. In the third experiment, the influence of the timing of 4-OHA treatment on its ability to improve the embryo count in hyperstimulated females was examined by introducing 4-OHA 24 h earlier, rather than at the time of hCG treatment. The results showed the importance of timing of 4-OHA administration, as 5000 microg/rat 4-OHA was able to restore embryo survival in the 40 PMSG hyperstimulated group only when it was administered 24 h before hCG injection. Together, these results highlighted that 4-OHA, when administered at the appropriate time and dose, could reverse the negative effects of hyperstimulation from PMSG on early embryonic development. This may be due to its potent aromatase inhibiting properties that lead to the suppression of oestrogen production, thereby alleviating the supraphysiological level of oestradiol, which is typically present in PMSG-treated females. Interestingly, 4-OHA treatment on its own was able to positively influence embryo count when given at a high dose of 5000 microg/rat, and this may be associated with its weak androgenic properties. In conclusion, this study supports the hypothesis that excessive oestradiol is responsible for the negative effects of hyperstimulation with PMSG on early embryonic development.
机译：使用芳香酶抑制剂4-羟基雄烯二酮（4-OHA）抑制内源性雌二醇的产生，研究了高雌二醇水平在调解妊娠母马血清促性腺激素（PMSG）过度刺激对大鼠早期胚胎发育的不良影响中的可能作用。 。在这项研究中进行了三个实验。首先，将不同剂量的4-OHA与人绒毛膜促性腺激素（hCG）一起施用给在发情期早期用20 IU PMSG过度刺激的发情前雌性大鼠，或单独向未过度刺激的发情前雌性大鼠给药。在高剂量1000、2000或5000微克/大鼠的情况下，4-OHA可以显着提高过度刺激雌性小鼠的胚胎存活率，而低剂量100和500微克/大鼠则无效。 4-OHA对胚胎计数的保护作用在2000微克时最佳。单独给药时，只有最高剂量的5000微克/大鼠4-OHA可以增加胚胎计数。在第二个实验中，研究了更高剂量的PMSG（30或40 IU），在注射hCG时给予或不给予5000 microg /大鼠4-OHA。事实证明，随着剂量的增加，PMSG的危害更大，在30个而非40个PMSG组中，5000微克/大鼠4-OHA能够使胚胎免于死亡。在第三个实验中，通过提前24小时而不是在hCG处理时引入4-OHA来检查4-OHA处理时间对其在过度刺激雌性中提高胚胎计数的能力的影响。结果显示了4-OHA给药时间的重要性，因为只有在注射hCG前24小时才给予5000μg/大鼠4-OHA才能恢复40 PMSG过度刺激组的胚胎存活。总之，这些结果表明，在适当的时间和剂量使用4-OHA可以逆转PMSG过度刺激对早期胚胎发育的负面影响。这可能是由于其有效的芳香酶抑制特性导致雌激素生成受到抑制，从而减轻了雌二醇的超生理水平，而雌二醇通常存在于经PMSG治疗的女性体内。有趣的是，当以高剂量5000 microg /大鼠给予4-OHA时，其自身能够对胚胎计数产生积极影响，这可能与其弱的雄激素特性有关。总之，这项研究支持以下假设：过量雌二醇是PMSG过度刺激对早期胚胎发育的负面影响的原因。

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