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 a major mechanism of calcium entry in somatic cells, known as store-operated calcium entry, is not necessary for calcium entry during oocyte maturation or at fertilization in mice. Instead, alternate channels are utilized including the voltage operated calcium channel, CaV3.2, and the transient receptor potential channel, TRPM7. 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 found that MED13 is essential for programming gene expression during early preimplantation embryo development; this work was published. These studies will shed light on basic genetic processes that can be disrupted by exposure to environmental chemicals and could impact on human fertility.

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9
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2019
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Miao, Yi-Liang; Gambini, Andrés; Zhang, Yingpei et al. (2018) Mediator complex component MED13 regulates zygotic genome activation and is required for postimplantation development in the mouse. Biol Reprod 98:449-464
Li, Yin; Hamilton, Katherine J; Wang, Tianyuan et al. (2018) DNA methylation and transcriptome aberrations mediated by ER? in mouse seminal vesicles following developmental DES exposure. Proc Natl Acad Sci U S A 115:E4189-E4198
Bernhardt, Miranda L; Stein, Paula; Carvacho, Ingrid et al. (2018) TRPM7 and CaV3.2 channels mediate Ca2+ influx required for egg activation at fertilization. Proc Natl Acad Sci U S A 115:E10370-E10378
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