Shawn L. Chavez
One of the major challenges since the introduction of human in vitro fertilization (IVF) over 35 years ago has been to select the embryo most suitable for transfer and likely to result in a normal term singleton pregnancy and 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 early embryogenesis greatly contributes to the low efficiency of IVF. Further support for this is provided by the estimate that only ~30% of natural human conceptions result in a live birth and chromosomal abnormalities have been reported in up to 70% of spontaneous miscarriages. Chromosomal mis-segregation in human oocytes (eggs) during meiosis has long been considered the primary cause for aneuploidy and embryonic loss, especially in cases of advanced maternal age. However, more recent studies of human embryos from women of average maternal age have established that mitotic errors occur at an equal or greater propensity than meiotic errors during embryonic cleavage divisions. The underlying mechanism(s) by which this occurs and whether there are corrective means, either naturally or therapeutically, to overcome chromosomal instability during pre-implantation development remains unknown and the primary focus of the Chavez laboratory.
Image of Nuclear structure and cellular sub-compartments in a rhesus pre-implantation embryo at the hatching blastocyst stage
We are 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 or be resolved during primate embryogenesis. Chavez and colleagues are also determining whether aneuploidy-causing factors can be detected earlier in oocytes, sperm and zygotes (fertilized oocytes) via alternative 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 determine if the lack of and/or aberrant inheritance of certain parental mRNAs, proteins or other factors may also impact chromosomal integrity and embryo developmental potential. In collaboration with other investigators at ONPRC and OHSU, we are also assessing the more long-term implications, including transgenerational inheritance of epigenetic changes or defects, of ovarian stimulation, IVF treatment and extended embryo culture as well as environmental influences, in offspring conceived from Assisted Reproductive Technologies (ART) and their subsequent generations. The findings from these studies also hold great promise for the placentation and stem cell research fields as the placenta-contributing trophectoderm layer is specified during pre-implantation development and similar mechanisms of chromosomal, genetic 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 Professor in the Division of Reproductive & Developmental Sciences at the Oregon National Primate Research Center (ONPRC) and in the Departments of Obstetrics & Gynecology and Physiology & Pharmacology at the Oregon Health & Science University (OHSU) School of Medicine. She is also a faculty member in the Center for Embryonic Cell and Gene Therapy at OHSU and an affiliate investigator in the Primate Genetics Section at ONPRC. Shawn 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, before joining the faculty at OHSU/ONPRC in 2013.
Daughtry, BL, and Chavez, SL. (2016) Chromosomal Instability in Mammalian Pre-implantation Embryos: Potential Causes, Detection Methods and Clinical Consequences. Cell and Tissue Research 363(1): 201-225. PMID: 26590822. PMC in process
Chavez, SL, McElroy, SL, Behr, B, Bossert, NL, De Jonge, CJ, Westphal, LM, Reijo Pera, RA. (2014) Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres. Human Molecular Genetics 23 (18): 4970-4984. PMCID: PMC4140471.
Chavez, SL, Loewke, KE, Han, J, Moussavi, F, Colls, P, Munne, S, Behr, B, Reijo Pera, RA. (2012) Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage. Nat Commun 3:1251. PMCID: PMC3535341.