Yvette Huet - US grants

Yvette Huet-Hudson IBN#9423382 The objective of the proposed research is to examine changes in gene expression in the pregant mouse uterus following exposure to the hormone estrogen. Estrogen is required for embryo implantation. Successful establishment of pregancy, resulting in the birth of healthy rodent offspring, depends upon normal implantation in the uterus. Implantation is a complex process regulated by the hormones progesterone and estrogen. The initiation of implantation is triggered in the progesterone-primed uterus by estrogen. One current theory is that progesterone/estrogen mediated regulation of embryo implantation is modulated indirectly through gene expression. It has also been shown that embryos require exposure to the maternal uterus within one hour of estrogen exposure for implantation to occur. In order to better understand how this process is initiated, this investigator will compare the genes that are expressed prior to, and one hour after, estrogen in a progesterone-primed uterus. This will be accomplished by producing uterine cDNA subtraction libraries. This will allow the investigaor to determine which genes are turned on or turned off by estrogen in the uterus during the critical one hour time period required for successful implantation. In gaining information concerning which genes are differentially expressed, it is hoped that a foundation will be laid for future studies of uterine physiology during early pregnancy. This new investigator, a minority scientist, has a strong background in reproductive biology, including a recent publication in the journal Proceedings of the National Academy. She will use this initiative funding to begin her independent investigation, in preparation for the submission of a full proposal.

DESCRIPTION (provided by applicant): A significant number of potential pregnancies are lost during the periimplantation stages of embryo development. It has been estimated by the Commission on Life Sciences of the National Research Council that more than 200,000 infants born each year in this country have abnormalities that arise during embryonic development. Other infants have markedly low birth weights which may result in death or disability later in postnatal life. A large portion of these abnormalities may result from alterations of normal embryonic development. Our studies have indicated that nitric oxide (NO) is required for preimplantation embryo development. In addition, exposure to estrogen, which induced implantation, increases the production of NO 10 fold in dormant blastocysts. However, little is known about the affect of NO on gene expression in periimplantation embryos. The purpose of the proposed experiments is to elucidate the integrated mechanisms regulated by NO in early embryonic development and initiation of implantation. This will be accomplished by conducting the following experiments: (a) Compare the localization of expression of the nitric oxide synthase (NOS) genes in embryos on days 1-4 of pregnancy (preimplantation). Results will indicate if induction of more than one NOS gene is required for NO production and if there is differential expression of these genes during preimplantation embryo; (b) Determine the nature of signaling cascades generated by NO in the embryo on days 1-4 of pregnancy. Specifically we will examine the effect, time course and cell specificity of cell cycle genes including: early immediate genes: c-los, c-jun and e-myc (mRNA and protein), cyclins (D,E, A and B) and retinoblastoma gene in response to NO. Results will determine if NO is acting through the activation of immediate early genes to genes regulating the cell cycle: (c) Determine if the inhibition of NO production alters expression of cell-cycle checkpoint genes. Determine the effect of inhibition of NO on the time course and cell specificity of levels of the cell-cycle checkpoint genes ATM, ATR, MAD and BUB in embryos on days 1-4 of pregnancy. Results will indicate if inhibition of NO stops normal mitotic division by altering expression of checkpoint genes. The proposed study will establish the status of NO production in the embryo and its effects on embryonic gene expression will generate important and meaningful information regarding normal and abnormal reproductive functions. Furthermore, this information should have implications in human fertility treatments, as a tool to select healthier IVF-derived embryos with increased probability for successful pregnancy.

Following a four-year self-study to explore equity, diversity, and inclusiveness, UNC Charlotte is poised for transformation into an institution where all faculty perceive that access to power, rewards, promotions, and leadership opportunities are equitably distributed.

Project goals are focused on the recruitment, retention, and advancement of women in STEM faculty positions and women in university-wide leadership positions. Strategies for change focus on structural reform, broad faculty awareness and engagement, and decision-maker accountability. A Faculty Affairs Office (FAO) will serve as a sustainable structural focal point for policy revision and a portfolio of programs designed to foster awareness, seek solutions, and disseminate project actions and outcomes. A competitive awards program will engage academic units to examine the status of women, including women faculty of color, and develop creative approaches for the specific needs of the unit. The FAO will be located in the Provost's Office to facilitate administrative accountability for making gains towards ADVANCE goals.