Environmental influence on reproductive biology and medicine

不同的环境化学物质会影响各种生物的繁殖能力，这取决于接触的时间和剂量，并且被认为也会影响人类的繁殖。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，他们不孕的根本原因尚不清楚。我们正在使用新生儿不育的染料木素模型来确定雌激素化合物如何影响雄性和雌性配子的成熟和功能，以及这些化合物如何影响着床期间的胚胎发育。

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.