One of the major challenges since the introduction of in vitro fertilization (IVF) has been to identify and select the embryo most suitable for transfer and likely to result in a normal term pregnancy, yielding a single healthy baby. Despite significant efforts to improve embryo assessment techniques and IVF success, the high incidence of aneuploidy (losses and/or gains of whole chromosomes) at the cleavage-stage of pre-implantation development greatly contributes to the low efficiency of IVF. Further support for this is provided by the notion that only 30% of natural conceptions result in a live birth and chromosomal abnormalities have been reported in up to 70% of spontaneous miscarriages. The underlying mechanism(s) by which this occurs and whether there are corrective means, either naturally or therapeutically, to overcome chromosomal instability at this stage of development remains unknown.
The Chavez laboratory is using a multi-disciplinary approach that combines live cell imaging, novel gene reporter and targeting technologies as well as single cell whole genome/transcriptome analyses to investigate how chromosomal abnormalities may arise during primate pre-implantation development. Chavez and colleagues are also determining whether aneuploidy can be detected earlier in oocytes (eggs), sperm and zygotes (fertilized oocytes) via biomedical optics or other non-invasive methods to avoid the unnecessary creation and/or transfer of embryos that are unlikely to advance in development. Additional aims of the Chavez laboratory are to assess the more long-term implications, including transgenerational inheritance of epigenetic changes or defects, of ovarian stimulation, in vitro oocyte maturation, IVF treatment and extended embryo culture in offspring conceived from Assisted Reproductive Technologies (ART) and subsequent generations. The findings from these studies also hold great promise for potential applications to the stem cell field, especially in the context of embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivation and differentiation, as similar mechanisms of chromosomal and epigenetic regulation may impact pluripotent stem cell biology.
Collectively, the goals of this research are to enhance our understanding of the genetic and epigenetic requirements of early embryogenesis across different species and improve IVF outcomes for the approximately 1 in 10 reproductive age couples in our population who are infertile.
Shawn L. Chavez is an Assistant Scientist in the Division of Reproductive & Developmental Sciences and Assistant Professor in the Departments of Obstetrics & Gynecology and Physiology & Pharmacology at the Oregon Health & Science University School of Medicine. She obtained her Ph.D. in Molecular, Cellular and Developmental Biology from Yale University, receiving the John Spangler Nicholas Dissertation Award upon graduation, and her B.S. with Honors and the Distinction in Major Award from the University of California, Santa Barbara as a Howard Hughes Medical Institute (HHMI) Fellow. She completed her Postdoctoral training at the University of California, San Francisco and Stanford University, where she was a Ruth L. Kirschstein National Research Service Award (NRSA) Fellow.
Ramathal,, C., Reijo Pera, R.A., Chavez, S.L.#. Preimplantation Embryo Development and Primordial Germ Line Specification in Physiology of Reproduction, 4th edition, J.D. Neill (Editor) Elsevier, 2014: In Press. #corresponding author
Goyal, A.*, Chavez, S.L.*#, Reijo Pera, R.A. Generation of human induced pluripotent stem cells using epigenetic regulators reveals a germ cell-like identity in partially reprogrammed colonies. PLoS ONE 2013 8(12): e82838. PMCID:
PMC3861446. *contributed equally; #corresponding author
Chavez, S.L., Loewke, K.E., Han, J., Moussavi, F., Colls, P., Munne, S., Behr, B., Reijo Pera, R.A. Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage. Nat Commun 2012 3:1251. PMCID: PMC3535341.
Tang, C., Lee, A.S., Volkmer, J.P., Sahoo, D., Nag, D., Mosley, A.R., Inlay, M.A., Ardehali, R., Chavez, S.L., Reijo Pera, R.A., Behr, B., Wu, J.C., Weissman, I.L., Drukker, M. SSEA-5, an antibody defining a novel surface glycan on human pluripotent stem cells and its application to remove teratoma-forming cells as part of a surface antibody panel. Nat Biotechnol 2011 (29) 9: 829-834. PMCID: PMC3537836.
McElroy, S.L., Byrne, J.A., Chavez, S.L., Behr, B., Hsueh, A.J., Westphal, L.M., Reijo Pera, R.A. Parthenogenic blastocysts derived from cumulus-free in vitro matured human oocytes. PLoS ONE 2010 5(6): 10979. PMCID: PMC2881862.