Iowa State University, 1994
Ovarian function - transcriptional and post-transcriptional gene regulation
Fertility control is a major health concern for premenopausal women. Research in my laboratory focuses on understanding the terminal events involved in follicular development and luteal tissue formation during a discrete period of the ovarian cycle referred to as the periovulatory period. During this short interval several major physiologic events occur, including ovulation, oocyte maturation and luteinization (i.e., differentiation of follicular to luteal cells). This period is also the major target of most pharmacological methods that disrupt or enhance fertility in women. While it is well established that the mid-cycle surge of luteinizing hormone (LH) triggers the events involved in ovulation and luteinization, much less is known about the genes, signaling cascades and regulatory mechanisms downstream of this endocrine event at the ovarian level. To understand the molecular and cellular aspects that regulate this highly spatiotemporal event, we are utilizing a variety of techniques, chromatin immunoprecipitation, microarray and computational analyses to identify novel target genes downstream of critical transcription factors (progesterone receptor and CCAAT-enhancer binding protein-b, early growth regulator-1/2) essential for ovulation. Additionally, a series of studies examining the role post-transcriptional gene regulation (i.e., ribonomics) plays in the ovulatory process has also been undertaken.
My laboratory has also entered the assisted reproductive technologies (ART) research arena, addressing the issue of embryo quality. In a first of its kind we have completed a proteomic (tandem mass spectrometry) analysis of conditioned medium from preimplantation embryos. The proteins identified are now being studied for their predictive value as well as their functional role in embryo development. This area of research has the potential to not only improve ART procedures but also the health of children conceived through ART.
Hong, X., L.J. Luense, L.K. McGinnis, W.B. Nothnick and L.K. Christenson. 2008. Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology, (Published Aug 7, 2008).
Fiedler, S.D., M.Z. Carletti, X. Hong and L.K. Christenson. 2008. Hormonal regulation of microRNA expression in periovulatory mouse mural granulosa cells. Biol. Reprod. (Published online, August 20, 2008)
Carletti, M. Z. and L.K Christenson. 2008. MicroRNA in the ovary and female reproductive tract. J. Anim. Sci. (Published online, September, 2008).
Huang A., M. Rudelius, S. Sharan, J.M. McAllister, M. Raffeld, L.K. Christenson, E. Sterneck. 2007. The Cebpd (C/EBPd) Gene Is Induced by Luteinizing Hormone in Ovarian Theca and Interstitial Cells But Is Not Essential for Mouse Ovary Function. PloS ONE 2(12): e1334 doi:10.1372/journal.pone.0001334
Zhang X., L.K. Christenson and Nothnick WB. 2007. Regulation of MMP-9 expression and activity in the mouse uterus by estrogen. Mol Reprod Dev 74 (3): 321-31.
Toulkunova, E., F. Cavaleri, S. Eckardt, R. Reinbold, L.K. Christenson, H.R. Scholer and A. Tomilin. 2006. The caudal-related protein Cdx2 promotes trophoblast differentiation of mouse ES cells. Stem Cells 24:139-144.
Hübner, K., G. Fuhrmann, L.K. Christenson, J. Kehler, R. Reinbold, R. De La Fuente, J.R. Wood, J.F. Strauss, III, M. Boiani and H.R. Schöler. 2003. Derivation of oocytes from mouse embryonic stem cells. Science, 300(5623):1251-1256. (May 23, 2003-Journal cover)
National Institutes of Child Health and Human Development [HD051870] and National Center for Research Resources [P20RR024214].