Effects of impending ovarian failure induced by 4-vinylcyclohexene diepoxide on fertility in C57BL/6 female mice.

Effects of impending ovarian failure induced by 4-vinylcyclohexene diepoxide on fertility in C57BL/6 female mice.
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DOI:
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发表时间:
2007-10
影响因子:
0.8
通讯作者:
Jamie R Haas;P. Christian;P. Hoyer
Jamie R Haas;P. Christian;P. Hoyer
中科院分区:
医学4区
文献类型:
--
作者:
Jamie R Haas;P. Christian;P. Hoyer

文献摘要

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小鼠每天重复给予4-乙烯基环己烯二环氧化物(VCD)可导致卵巢衰竭的逐渐发作,为围绝经期提供了模型。由于越来越多的妇女推迟开始家庭,老年妇女的不孕症令人担忧。本研究旨在确定卵巢衰竭对VCD治疗小鼠生育力的影响。雌性C57 BL/6 J小鼠每天(17天)给予溶剂对照或VCD(160 mg/kg,腹腔内)以消耗原始卵泡,然后分为2组。第1组在给药后不久交配;第2组在给药后第20天交配,此时卵巢即将衰竭。在妊娠第16天评价生育力。在第1组中,周期长度,妊娠率和活胎数在VCD处理的动物和对照组之间没有差异,但VCD处理的小鼠需要更多的交配才能怀孕,并有更多的吸收。在第2组中,VCD处理的小鼠表现出发情前期和交配栓,但只有1只动物妊娠,并且没有活胎。妊娠和非妊娠对照组的卵巢含有相似数量的卵泡和黄体。VCD处理动物的卵巢不含卵泡,仅在妊娠动物中观察到黄体。在给药后不久交配的VCD处理小鼠中,受孕更困难,观察到更多吸收的胎儿,而在接近卵巢衰竭的小鼠中,未成功妊娠。这些结果表明,VCD处理的小鼠可用于模拟围绝经期妇女的不孕症。
Repeated daily dosing of mice with 4-vinylcyclohexene diepoxide (VCD) causes a gradual onset of ovarian failure, providing a model for perimenopause. Because increasing numbers of women are delaying starting a family, infertility in aging women is of concern. This study was designed to determine the effects of impending ovarian failure on fertility in VCD-treated mice. Female C57BL/6J mice were dosed daily (17 d) with vehicle control or VCD (160 mg/kg, intraperitoneally) to deplete primordial follicles and then were divided into 2 groups. Group 1 was mated soon after dosing; group 2 was mated on day 20 after dosing, during impending ovarian failure. Fertility was evaluated on gestational day 16. In group 1, cycle length, pregnancy rate, and number of live fetuses did not differ between VCD-treated animals and controls, but VCD-treated mice required more matings to become pregnant and had more resorptions. In group 2, VCD-treated mice demonstrated proestrus and copulatory plugs, but only 1 animal became pregnant, and she had no viable fetuses. Ovaries from pregnant and nonpregnant controls contained similar numbers of follicles and corpora lutea. Ovaries from VCD-treated animals contained no follicles, and corpora lutea were seen only in pregnant animals. In VCD-treated mice mated soon after dosing, conception was more difficult and more resorbed fetuses were seen, whereas in those mated closer to impending ovarian failure, no successful pregnancies were achieved. These results demonstrate that VCD-treated mice can be used to model infertility in perimenopausal women.