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A bovine model to study reproductive aging.

机译:研究生殖老化的牛模型。

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摘要

Decline in fertility with age has been well documented in women. There are ethical limitations to use humans as a model for basic research, and there is a lack of well characterized animal model. The objective was to characterize and validate a bovine model for the study of age-associated subfertility. All experiments were conducted on the same group of 13-14 year old cows (n=10), and their 1-4 year old young daughters (n=10). Mother-daughter pairs were used to reduce genetic variations.; Follicular wave pattern in a natural reproductive cycle was maintained in old cows similar to that in daughters. We hypothesized that aging in cattle is associated with elevated circulating concentrations of FSH, and reduced concentrations of steroid hormones. As stated, circulating FSH concentrations were higher (P=0.009) during follicular waves in old than young cows. The ovulatory follicle in 2-wave cycles was smaller in old cows (P=0.04), but plasma estradiol concentrations were higher (P=0.01). Luteal phase progesterone tended to be lower in old than young cows (P=0.1). The number of 4-5 mm follicles recruited into a follicular wave was lower (P0.05) in old cows than in their daughters.; The response to ovarian synchronization and superstimulatory treatments was compared between old and young cows. We hypothesized that aging in cattle is associated with decreased synchrony of an induced follicular wave after steroid treatment. Conversely, the emergence of an induced follicular wave was synchronous between age groups. The preovulatory LH surge was delayed in old compared to young cows (P=0.01), but the detected ovulation times were not different. Old cows had fewer (P0.01) follicles ≥6 mm after superstimulation, and tended (P=0.1) to have fewer ovulations than their daughters (32+/-4 versus 40+/-3, respectively). The response of individual cows to successive superstimulatory treatments was correlated (r>0.8; P0.0001).; The hypothesis of reduced oocyte developmental competence in old cows was tested by comparing embryo production and pregnancy rates between old and young cows. Fewer (P=0.04) embryos were recovered from old cows (6+/-2) than their daughters (12+/-2). A higher proportion (P0.01) of unfertilized oocytes and/or uncleaved zygotes were recovered from old cows (222/312, 71%) than their daughters (119/316, 38%). The recovery of fewer embryos in old cows suggests reduced oocyte developmental competence. The survival of embryos after transfer into unrelated young recipients was similar between age groups.; The effects of advanced age on oocyte meiotic maturation and oocyte chromosome numbers abnormalities were studied in old and young cows. Our hypothesis of compromised oocyte meiotic maturation with age was not supported; similar or higher proportion of metaphase II oocytes were recovered from old than young cows. The abnormalities of oocyte chromosomal numbers were similar between age groups.; To conclude, endocrine, follicular and oocyte developmental changes in old cows are consistent with those reported for women approaching menopause. Therefore, our results validated the use of a bovine model to study age-associated subfertility in women. Unlike women, we did not detect an age-related increase in abnormalities of oocyte chromosome numbers in cattle.
机译:妇女的生育能力随着年龄的增长而下降。使用人类作为基础研究的模型在伦理上有局限性,并且缺乏特征明确的动物模型。目的是鉴定和验证用于研究年龄相关性亚生育力的牛模型。所有实验均在同一组13-14岁的母牛(n = 10)及其1-4岁的小女儿(n = 10)上进行。母女对用于减少遗传变异。老奶牛的自然生殖周期中的卵泡波动模式与女儿相似。我们假设牛的衰老与FSH循环浓度升高和类固醇激素浓度降低有关。如上所述,在卵泡波中,老年母牛的循环FSH浓度较高(P = 0.009)。在两波周期中,成年母牛的排卵卵泡较小(P = 0.04),但血浆雌二醇浓度较高(P = 0.01)。黄体期孕酮往往比年幼的母牛低(P = 0.1)。老年母牛的卵囊波募集的4-5 mm卵泡数量比其女儿的要低(P <0.05)。比较了老龄和幼龄母牛对卵巢同步和超刺激疗法的反应。我们假设牛的衰老与类固醇治疗后诱导的卵泡波同步性降低有关。相反,在各个年龄组之间,卵泡波的诱导是同步的。与年轻母牛相比,成年母牛的排卵前LH潮变被延迟了(P = 0.01),但是检测到的排卵时间没有差异。超级刺激后,成年母牛的≥6mm卵泡较少(P <0.01),并且趋于(P = 0.1)的排卵量比其女儿少(分别为32 +/- 4和40 +/- 3)。个体母牛对连续超级刺激治疗的反应是相关的(r> 0.8; P <0.0001)。通过比较成年和成年母牛的胚胎产量和妊娠率,检验了成年母牛卵母细胞发育能力降低的假说。从成年母牛(6 +/- 2)中恢复的胚胎(12 +/- 2)少(P = 0.04)。从老牛(222 / 312,71%)中回收的未受精卵母细胞和/或未裂解的受精卵的比例高于其女儿(119 / 316,38%)。老奶牛较少胚胎的恢复表明卵母细胞发育能力降低。不同年龄组之间的胚胎移植到无关的年轻受体后的存活率相似。研究了高龄对成年和成年母牛的卵母细胞减数分裂成熟和卵母细胞染色体数目异常的影响。我们的假说认为,随着年龄的增长,卵母细胞减数分裂成熟受损。从年老的母牛中恢复出相似或更高比例的中期II卵母细胞。不同年龄组的卵母细胞染色体数目异常相似。总之,老奶牛的内分泌,卵泡和卵母细胞发育变化与绝经期妇女的报道一致。因此,我们的结果验证了使用牛模型研究女性年龄相关的不育性。与女性不同,我们没有发现与年龄相关的牛卵母染色体数目异常增加。

著录项

  • 作者

    Malhi, Pritpal Singh.;

  • 作者单位

    The University of Saskatchewan (Canada).;

  • 授予单位 The University of Saskatchewan (Canada).;
  • 学科 Biology Animal Physiology.; Biology Veterinary Science.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 138 p.
  • 总页数 138
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生理学;动物学;
  • 关键词

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