Environmental influence on reproductive biology and medicine

不同的环境化学品可以影响各种生物的生殖能力，这取决于暴露的时间和剂量，并且被认为也会影响人类生殖。 一个例子是植物雌激素，染料木黄酮，当给予新生雌性小鼠时，对它们的繁殖能力有长期影响。然而，他们不育的根本原因尚不清楚。 我们正在使用新生儿金雀异黄素不育模型来确定雌激素化合物如何影响男性和女性配子的成熟和功能，以及这些化合物如何影响胚胎发育，通过植入的时间。 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卵激活的早期事件（例如，减数分裂的恢复、皮质颗粒胞吐、母体mRNA的募集）和足月子宫内发育的发生。 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。我们正计划研究人类精子样本中PLC zeta功能的各个方面。我们假设缺乏足够的PLC zeta活性来诱导卵子激活所需的适当钙振荡可以解释不孕夫妇的失败，包括受精失败，植入前胚胎发育不良，甚至临床妊娠后流产。 钙的波动也受鸡蛋内因素的控制。 正在使用小鼠模型进行其他研究，以检查卵子内负责控制钙再吸收的分子，这一过程对于受精时钙振荡的持续至关重要。 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。

Different environmental chemicals can affect the reproductive capability of a variety of organisms, depending on the timing and dose of exposure, and are thought to impact human reproduction as well. One example is the phytoestrogen, genistein, which when given to neonatal female mice has long-term effects on their ability to reproduce. The underlying causes of their infertility, however, are not known. We are using the neonatal genistein model of infertility to determine how estrogenic compounds affect male and female gamete maturation and function, and how these compounds influence embryo development through the time of implantation. 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 (e.g., resumption of meiosis, cortical granule exocytosis, recruitment of maternal mRNAs) 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. We are planning to study aspects of PLC zeta function in human sperm samples. We hypothesize that a lack of sufficient PLC zeta activity to induce appropriate calcium oscillations required for egg activation could explain a spectrum of failure for the infertile couple, including failed fertilization, poor preimplantation embryo development, and even clinical pregnancy followed by miscarriage. Calcium oscillations are also controlled by factors within the egg. Additional studies are being performed using the mouse model to examine molecules within the egg that are responsible for controlling calcium reuptake, a process that is essential for the continuation of calcium oscillations at 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.