GM-CSF Regulation of Preimplantation Embryo Development

使用试管受精技术治疗不孕症已经取得了巨大的成功。然而，人们主要关注的是多胎妊娠的高发生率(由移植一个以上的胚胎引起)，以及通过这项技术怀孕的成年人可能产生的不利健康后果。多胎妊娠使母亲和婴儿面临巨大的风险，产科护理增加，早产，新生儿护理增加，以及脑瘫等神经疾病。这可以通过移植单个胚胎来克服。然而，患者和临床期望是，单胚胎移植应该在妊娠率几乎没有下降的情况下实现，目前这是不可能的，因为我们的胚胎培养方法不够充分。在动物身上的研究表明，哺乳动物胚胎的实验室发育可能会导致小于胎龄的婴儿(即使考虑到多胞胎的影响)。这一点得到了最近的研究的支持，这些研究一致认为，通过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更高相关，特别是随着年龄超过40岁。然而，目前年龄最大的试管婴儿年龄为23岁。此前，我们已经证明了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著的有益影响。此外，我们已经在小鼠身上表明，胚胎暴露于GM-CSF可以减轻体外培养对胎儿生长和出生后身体结构的不利副作用。我们的研究现在集中在了解这种蛋白质为什么对胚胎生长有益，并测试我们是否可以提高怀孕率，并通过移植经过GM-CSF处理的单个胚胎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.