GM-CSF Regulation of Preimplantation Embryo Development

使用IVF技术治疗不孕症已经取得了巨大的成功。然而，人们对多胎妊娠（由一个以上胚胎移植引起）的高发生率以及通过这种技术怀孕的成年人的潜在不良健康后果表示严重关切。多胎妊娠使母亲和婴儿都面临巨大的风险，产科护理增加，早产，新生儿护理增加和大脑性麻痹等神经系统疾病。这可以通过移植单个胚胎来克服。然而，患者和临床的期望是，单胚胎移植应该在妊娠率几乎没有降低的情况下实现，目前这是不可能的，因为我们培养胚胎的方法是不够的。动物研究表明，哺乳动物胚胎的实验室生长可能导致小于胎龄婴儿（即使考虑到多胞胎的影响）。最近的研究表明，试管婴儿出生的婴儿比预期的要小。这可能会导致晚年的健康问题，因为出生时身材矮小与心血管疾病和糖尿病的风险较高有关，特别是随着年龄的增长超过40岁。然而，目前年龄最大的IVF儿童是23岁。以前，我们已经表明，一种蛋白质生长因子，称为粒细胞-巨噬细胞集落刺激因子（GM-CSF），通常在生殖道中发现，对实验室中生长的人类和小鼠胚胎具有显着的有益作用。此外，我们已经在小鼠中表明，胚胎暴露于GM-CSF会增加体外培养对胎儿生长和出生后身体结构的有害副作用。我们的研究现在集中在了解为什么这种蛋白质对胚胎生长有益，并测试我们是否可以通过移植GM-CSF处理的单个胚胎来提高妊娠率并产生正常健康的婴儿。

Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.