This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Presently, -1% of children born each year in the USA are conceived via assisted reproductive technologies (ART) and world-wide >1 million children have been conceived and delivered over the last 2 decades. Children conceived through ART are more likely to exhibit low birth weights and to be delivered prematurely.Much of the morbidity that stems from ART is due to the high rate of multiple gestations associated with this treatment. To date, embryo quality assessments are based on a subjective morphological evaluation of the embryo following in vitro culture. Objective criteria for selection of high quality embryos should increase ART success and make single embryo transfer a more viable therapeutic option. Thus, there is a compelling case for the development of analytical and non-invasive assays that predict embryo quality. The long-range goal of this research is to link molecular, cellular and biochemical processes occurring in the early embryo prior to implantation to developmental events that ultimately result in a successful pregnancy. The hypothesis of theproposed research is that the early embryo secretes/releases proteins that reflect the developmental competence of that embryo. This proposal will identify en masse for the first time early embryonic secreted/ released protein markers in conditioned medium to begin to establish a signature/pattern of proteins indicative of embryo quality.
Aim 1 will identify secreted/released protein(s) from murine embryos exhibitingqualitative differences using tandem mass spectrometry.
Aim 2 will validate whether these proteins can be used to predict in vivo embryo quality and whether the murine system is translatable to the human system. Furthermore, we will establish a human embryonic conditioned medium bank from single embryo transfers that will allow us to establish a relationship between protein profiles and pregnancy outcome. Children conceived using assisted reproductive technologies (ART) are at a greater risk for birth defects and premature delivery and low birth weights. Identification of factors that can predict embryo quality will provide objective criteria for embryo selection and will reduce the number multiple birth pregnancies (by facilitating single embryo transfer). The long-term benefits are the development of safe methods for determining embryo quality, improvement of ART methods and ultimately improving the health of the childrenconceived through ART.
|Pohler, Ky G; Green, Jonathan A; Moley, Laura A et al. (2017) Circulating microRNA as candidates for early embryonic viability in cattle. Mol Reprod Dev 84:731-743|
|Rogers, Robert S; Tungtur, Sudheer; Tanaka, Tomohiro et al. (2017) Impaired Mitophagy Plays a Role in Denervation of Neuromuscular Junctions in ALS Mice. Front Neurosci 11:473|
|Navakanitworakul, Raphatphorn; Hung, Wei-Ting; Gunewardena, Sumedha et al. (2016) Characterization and Small RNA Content of Extracellular Vesicles in Follicular Fluid of Developing Bovine Antral Follicles. Sci Rep 6:25486|
|Aleksandrova, Anastasiia; Czirok, Andras; Kosa, Edina et al. (2015) The endoderm and myocardium join forces to drive early heart tube assembly. Dev Biol 404:40-54|
|Nishimune, Hiroshi; Stanford, John A; Mori, Yasuo (2014) Role of exercise in maintaining the integrity of the neuromuscular junction. Muscle Nerve 49:315-24|
|Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina et al. (2014) Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice. Proc Natl Acad Sci U S A 111:5735-40|
|Zhang, Yu-Kun Jennifer; Lu, Hong; Klaassen, Curtis D (2013) Expression of human CAR splicing variants in BAC-transgenic mice. Toxicol Sci 132:142-50|
|Elsarraj, Hanan S; Hong, Yan; Valdez, Kelli et al. (2013) A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. J Cell Sci 126:2446-58|
|Galvin-Burgess, Katherine E; Travis, Emily D; Pierson, Kelsey E et al. (2013) TGF-?-superfamily signaling regulates embryonic stem cell heterogeneity: self-renewal as a dynamic and regulated equilibrium. Stem Cells 31:48-58|
|Nishimune, Hiroshi (2012) Active zones of mammalian neuromuscular junctions: formation, density, and aging. Ann N Y Acad Sci 1274:24-32|
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