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 including the voltage operated calcium channel, CaV3.2, are utilized. 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.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
U.S. National Inst of Environ Hlth Scis
Zip Code
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
Schultz, Richard M; Stein, Paula; Svoboda, Petr (2018) The oocyte-to-embryo transition in mouse: past, present, and future. Biol Reprod 99:160-174
Tang, Shuang; Fang, Yi; Huang, Gang et al. (2017) Methionine metabolism is essential for SIRT1-regulated mouse embryonic stem cell maintenance and embryonic development. EMBO J 36:3175-3193
Bernhardt, Miranda L; Padilla-Banks, Elizabeth; Stein, Paula et al. (2017) Store-operated Ca2+ entry is not required for fertilization-induced Ca2+ signaling in mouse eggs. Cell Calcium 65:63-72
Gambini, Andrés; Williams, Carmen J (2016) LUTs of blastocyst nuclei cell for quantification. Mol Reprod Dev 83:575
Zheng, Xiaofeng; Yang, Pengyi; Lackford, Brad et al. (2016) CNOT3-Dependent mRNA Deadenylation Safeguards the Pluripotent State. Stem Cell Reports 7:897-910
Suen, Alisa A; Jefferson, Wendy N; Wood, Charles E et al. (2016) SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer. Mol Cancer Res 14:849-58
Jensen, E T; Daniels, J L; Stürmer, T et al. (2015) Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study. BJOG 122:1349-61

Showing the most recent 10 out of 22 publications