Oxygen, oxidative phosphorylation and regulation of embryo development.

令人关切的是，需要在实验室中培育胚胎的人类不孕症治疗，如用于人类体外受精，可能在胎儿发育期间造成问题，甚至可能在成年后很长一段时间内导致健康问题。特别是，与十年前相比，许多诊所现在在体外培养人类胚胎的时间延长了几天（以选择最好的胚胎进行移植）。有证据表明，胚胎生长的环境会影响某些基因的开启和关闭。在早期发育的适当时间正常的开关应该会导致健康的后代。关闭或打开失败，或者不适当的时机，可能会导致在开发后期表现出来的后果。我们认为，氧气浓度和线粒体（细胞将氧气转化为能量的细胞器）的活性是早期胚胎发育过程中基因开启和关闭的关键调节因子。这是因为我们已经证明，在一个与人类胚胎代谢相似的物种的胚胎中，氧气浓度和线粒体活性需要随着胚胎在实验室中的最佳发育而改变。在其他哺乳动物细胞中，氧和线粒体的活性可以打开或关闭几个特定的基因，也就是转录因子。转录因子是调节其他基因的基因。因此，转录因子是早期胚胎发育的良好调控因子。目前的项目旨在确定在胚胎实验室生长过程中改变氧浓度和线粒体活性等因素是否会影响这些转录因子的开启和关闭方式。如果我们发现这是真的，人类胚胎在实验室中的生长方式需要仔细检查，以尽量减少可能对胎儿造成长期后果的风险。

There is concern that human infertility treatment requiring the growth of embryos in the laboratory, as applied in human IVF, may cause problems during fetal development or even possibly lead to health problems much later in life as an adult. In particular, many clinics are now growing human embryos outside the body for several days longer (to select the best embryos for transfer) than what occurred a decade ago. This concern is based on the evidence that the environment in which an embryo grows in has an impact on the way in which some genes are switched on and off. Normal on-off switching at appropriate times during early development should lead to healthy offspring. Failure to turn off or on, or inappropriate timing, may lead to consequences that manifest themselves later in development. We believe that oxygen concentration and the activity of mitochondria, the organelles of cells that converts oxygen into energy, are key regulators in turning on and off genes during early embryo development. This is because we have shown that, in embryos of a species that is metabolically similar to the human embryo, oxygen concentration and mitochondria activity need to change as the embryo grows for optimal development in the laboratory. In other mammalian cells, oxygen and mitochondria activity are known to turn on or off several particular genes, known as transcription factors. Transcription factors are genes which regulate other genes. Therefore, transcription factors are good candidates as regulators of early embryo development. The present project aims to determine if factors such as changing oxygen concentration and mitochondria activity during laboratory growth of embryos affects the way in which these transcription factors turn on and off. If we find this is true, the way in which human embryos are grown in the laboratory needs to be examined carefully to minimize the risk of possible long-term consequences to the resulting fetus.