Armstrong D T
University of Adelaide, Department of Obstetrics and Gynaecology, The Queen Elizabeth Hospital, Woodville, Australia.
Theriogenology. 2001 Apr 1;55(6):1303-22. doi: 10.1016/s0093-691x(01)00484-8.
The widespread use of a variety of assisted reproductive technologies has removed many of the constraints that previously restricted mammalian reproduction to the period between onset of puberty and reproductive senescence. In vitro embryo production systems now allow oocytes from very young animals to undergo fertilization and form embryos capable of development to normal offspring, albeit at somewhat reduced efficiencies compared to oocytes from adult females. They also can overcome infertility associated with advanced age of animals and women. This review examines oocyte developmental competence as the limiting factor in applications of assisted reproductive technologies for both juvenile and aged females. Age of oocyte donor is a significant factor influencing developmental competence of the oocyte. Age-related abnormalities of oocytes include a) meiotic incompetence or inability to complete meiotic maturation resulting in oocytes incapable of fertilization; b) errors in meiosis that can be compatible with fertilization but lead to genetic abnormalities that compromise embryo viability; and c) cytoplasmic deficiencies that are expressed at several stages of development before or after fertilization. In general, oocytes from juvenile donors and the embryos derived therefrom appear less robust and may be less tolerant to suboptimal handling and in vitro culture conditions than are adult oocytes. Research to identify specific cytoplasmic deficiencies of juvenile oocytes may enable modifications of culture conditions to correct such deficiencies and thus enhance developmental competence. Use of oocytes from aged donors for assisted reproduction can have a variety of applications such as extending the reproductive life of individual old females whose offspring still have high commercial value, and conservation of genetic resources such as rare breeds of livestock and endangered species. In general, female fertility decreases with advancing age. Studies of women in oocyte donation programs have established reduced oocyte competence as the major cause of declining fertility with age, although inadequate endometrial function can also be a contributing factor. Most research has emphasized the importance of chromosomal abnormalities because of the well established increase in aneuploidy with increasing maternal age but little is known about the underlying cellular and molecular mechanisms. Research aimed at identifying the specific developmental deficiencies of oocytes from juvenile donors and abnormalities of oocytes from aged females will assist in overcoming present bottlenecks that limit the efficiency of assisted reproduction technologies. Such research will also be crucial to the development of new oocyte-based technologies for overcoming infertility and possibly subverting chromosomal abnormalities in women approaching menopause.
多种辅助生殖技术的广泛应用消除了许多以前将哺乳动物繁殖限制在青春期开始至生殖衰老期间的限制因素。体外胚胎生产系统现在允许非常年幼动物的卵母细胞进行受精并形成能够发育为正常后代的胚胎，尽管与成年雌性动物的卵母细胞相比，其效率有所降低。它们还可以克服与动物和女性高龄相关的不孕症。本综述将卵母细胞发育能力视为辅助生殖技术在幼年和老年雌性动物应用中的限制因素进行研究。卵母细胞供体的年龄是影响卵母细胞发育能力的一个重要因素。与年龄相关的卵母细胞异常包括：a）减数分裂无能或无法完成减数分裂成熟，导致卵母细胞无法受精；b）减数分裂错误，虽可受精但会导致损害胚胎活力的遗传异常；c）在受精前后的几个发育阶段表现出的细胞质缺陷。一般来说，幼年供体的卵母细胞及其衍生的胚胎似乎不如成年卵母细胞强壮，对次优处理和体外培养条件的耐受性可能也较差。识别幼年卵母细胞特定细胞质缺陷的研究可能有助于修改培养条件以纠正此类缺陷，从而提高发育能力。使用老年供体的卵母细胞进行辅助生殖有多种应用，例如延长其后代仍具有高商业价值的个体老年雌性的生殖寿命，以及保护遗传资源，如珍稀品种的家畜和濒危物种。一般来说，雌性生育能力会随着年龄的增长而下降。对参与卵母细胞捐赠项目女性的研究已确定，卵母细胞能力下降是随着年龄增长生育能力下降的主要原因，尽管子宫内膜功能不足也可能是一个促成因素。大多数研究都强调了染色体异常的重要性，因为随着母亲年龄的增加，非整倍体明显增加，但对潜在的细胞和分子机制知之甚少。旨在识别幼年供体卵母细胞的特定发育缺陷和老年雌性卵母细胞异常的研究将有助于克服目前限制辅助生殖技术效率的瓶颈。此类研究对于开发新的基于卵母细胞的技术以克服不孕症以及可能颠覆接近更年期女性的染色体异常也至关重要。
