Environmental influence on gametes and embryos

哺乳动物受精的一个普遍特征是，精子在卵中引起一系列重复的钙振荡，持续数小时，并以原核形成终止。小鼠中的这种钙振荡模式对于响应于受精的卵激活的早期事件和发生的足月子宫内发育都是必不可少的。精子内负责诱导这些钙振荡的因子是睾丸特异性磷脂酶C，PLC zeta，其在精卵质膜融合后从精子头部释放，并且在迄今为止研究的所有哺乳动物精子中发现，包括人类。钙的波动也受鸡蛋内因素的控制。正在使用小鼠模型进行研究，以检查卵子内负责控制钙振荡行为和钙再吸收的分子，这些过程对于受精时钙振荡的持续至关重要。我们发现，在成熟过程中，卵子通过低电压T型钙通道摄取钙，这种钙摄取调节受精时观察到的钙振荡模式。我们还发现，一种名为RGS2的蛋白质有助于防止卵子在受精前释放钙。我们预计，通过更好地了解卵子激活过程中钙振荡行为的分子和细胞调节模式，我们可以了解早期胚胎发育如何被环境因素和疾病状态改变。 许多必需分子由休眠直到卵母细胞成熟的母体mRNA编码。其中一种分子，MED13，是介体复合物的一个组成部分，与RNA聚合酶相互作用以调节转录。我们目前正在研究MED13在早期植入前胚胎发育过程中编程基因表达的功能。这些研究将揭示暴露于环境化学品可能会破坏的基本遗传过程，并可能影响人类生育能力。

A universal feature of fertilization in mammals is that the fertilizing sperm evokes a series of repetitive calcium oscillations in the egg that persist for several hours and terminate with pronucleus formation. This pattern of calcium oscillations in mice is essential for both early events of egg activation in response to fertilization and for full term intrauterine development to occur. The factor within sperm responsible for inducing these calcium oscillations is a testis-specific phospholipase C, PLC zeta, which is released from the sperm head after sperm-egg plasma membrane fusion, and is found in all mammalian sperm studied to date, including human. Calcium oscillations are also controlled by factors within the egg. Studies are being performed using the mouse model to examine molecules within the egg that are responsible for controlling calcium oscillation behavior and calcium reuptake, processes that are essential for the continuation of calcium oscillations at fertilization. We found that during maturation, eggs take up calcium via low voltage, T-type calcium channels and that this calcium uptake regulates the calcium oscillatory pattern observed at fertilization. We also found that a protein named RGS2 helps prevent the egg from releasing calcium prior to fertilization. We anticipate that by achieving a better understanding of the molecular and cellular modes of regulation of calcium oscillatory behavior during egg activation, we can learn how early embryo development is altered by environmental factors and by disease states. A number of essential molecules are encoded by maternal mRNAs that are dormant until oocyte maturation. One of these molecules, MED13, is a component of the Mediator complex that interacts with RNA polymerase to regulate transcription. We are currently examining the function of MED13 in programming gene expression during early preimplantation embryo development. These studies will shed light on basic genetic processes that can be disrupted by exposure to environmental chemicals and could impact on human fertility.