van Cappellen W A, Kramer P, van Leeuwen E C, de Leeuw R, de Jong F H
Department of Endocrinology & Reproduction, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.
Hum Reprod. 1997 Feb;12(2):224-30. doi: 10.1093/humrep/12.2.224.
The objective of this study was to set up a superovulation protocol in adult cyclic rats by using recombinant human follicle stimulating hormone (rhFSH; Org32489). Good results were obtained by treatment with decreasing doses of rhFSH (2.5 to 0.5 IU) during the dioestrus period. The number of corpora lutea (CL) found in rats treated with this protocol was 43.5 +/- 3.4; this is more than three times the number in saline-treated control rats (13.0 +/- 0.4). Fertilization of oocytes after superovulation was as good as after normal ovulation in terms of number of 2-cell stage embryos found 2 days after mating. The absolute number of implantations was twice the number observed in saline-treated control rats (23.3 +/- 1.8 versus 10.6 +/- 0.5); therefore the number of implantations per CL was lower in superovulated rats. The serum concentrations of luteinizing hormone (LH), endogenous FSH and oestradiol-17beta were decreased during rhFSH treatment, while the inhibin serum concentration was increased. The progesterone serum concentration was increased on the days of pro-oestrus and oestrus after treatment. No difference was observed in the testosterone serum concentration. Pretreatment with 10 IU rhFSH at oestrus before giving the decreasing doses of rhFSH during dioestrus reduced the ovulatory response. Finally, treatment with a constant low dose of rhFSH instead of a decreasing dose of rhFSH did not result in spontaneous ovulation. However, ovulation induction by means of a human chorionic gonadotrophin bolus resulted in superovulation in six out of eight rats. It is concluded that superovulation in cyclic rats can be achieved using rhFSH treatment. However, it was found that the type of rhFSH regimen was very important to achieve appropriate stimulation. The optimal protocol was treatment with decreasing doses of rhFSH during dioestrus. The oocytes retrieved could be fertilized as well as oocytes of saline-treated control rats. The results also indicate that treatment with higher doses of rhFSH might induce a desensitization for FSH and LH.
本研究的目的是通过使用重组人促卵泡激素（rhFSH；Org32489）在成年周期性大鼠中建立一种超排卵方案。在动情后期用递减剂量的rhFSH（2.5至0.5 IU）进行治疗取得了良好的效果。用该方案治疗的大鼠中发现的黄体（CL）数量为43.5±3.4；这是生理盐水处理的对照大鼠（13.0±0.4）数量的三倍多。超排卵后卵母细胞的受精情况在交配后2天发现的2细胞期胚胎数量方面与正常排卵后一样好。着床的绝对数量是生理盐水处理的对照大鼠中观察到的数量的两倍（23.3±1.8对10.6±0.5）；因此，超排卵大鼠中每个CL的着床数量较低。在rhFSH治疗期间，黄体生成素（LH）、内源性FSH和雌二醇-17β的血清浓度降低，而抑制素血清浓度升高。治疗后在发情前期和发情期的日子里孕酮血清浓度升高。睾酮血清浓度未观察到差异。在动情后期给予递减剂量的rhFSH之前，在发情期用10 IU rhFSH进行预处理会降低排卵反应。最后，用恒定低剂量的rhFSH而不是递减剂量的rhFSH进行治疗不会导致自发排卵。然而，通过人绒毛膜促性腺激素推注诱导排卵在八只大鼠中有六只导致了超排卵。得出的结论是，使用rhFSH治疗可以在周期性大鼠中实现超排卵。然而，发现rhFSH方案的类型对于实现适当的刺激非常重要。最佳方案是在动情后期用递减剂量的rhFSH进行治疗。回收的卵母细胞与生理盐水处理的对照大鼠的卵母细胞一样能够受精。结果还表明，用更高剂量的rhFSH进行治疗可能会诱导对FSH和LH的脱敏。
