Environmental influence on gametes and embryos

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

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. 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. Plasma membrane calcium ATPases are critical mediators of calcium signaling at fertilization. We are examining the impact of severe disruption of this function on epigenetic reprogramming of the preimplantation embryo and on offspring health. In ongoing studies, we are determining mechanisms by which calcium fluxes are regulated following fertilization and the impact of alterations in these fluxes on offspring development and health. 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. Many essential molecules are encoded by maternal mRNAs that are recruited for translation during oocyte maturation and critically important for fertilization and the early steps of embryonic development. One of these steps, embryonic genome activation (EGA), is orchestrated by an intrinsic developmental program initiated during oocyte maturation, but we have an incomplete understanding of how the transcriptional machinery and/or sequence-specific transcription factors dictate the timing of EGA in mammals and contribute to developmental potential. We found that calcium signals alter new transcription from the embryonic genome, explaining at least some of the impact on embryo development; this work was published as a preprint. Our ongoing work is focused on the role of calcium signaling and additional transcription factors in regulating EGA and preimplantation embryo health. These studies shed light on basic genetic processes that can be disrupted by exposure to environmental chemicals and could impact human fertility and other human disease states.