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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #305831
Title: Systems biology approaches to understanding conceptus elongation and early pregnancy loss

Author
item SPENCER, THOMAS - Washington State University
item Geary, Thomas
item HANSEN, PETER - University Of Florida
item NEIBERGS, HOLLY - Washington State University
item DALTON, JOSEPH - University Of Idaho
item Cole, John

Submitted to: Society for the Study of Reproduction Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 7/19/2014
Publication Date: 7/19/2014
Citation: Spencer, T.E., Geary, T.W., Hansen, P.J., Neibergs, H., Dalton, J., Cole, J.B. 2014. Systems biology approaches to understanding conceptus elongation and early pregnancy loss. Society for the Study of Reproduction Annual Meeting. Grand Rapids, MI, July 19-23, abstr. 64. 2014.

Interpretive Summary:

Technical Abstract: Infertility and subfertility represent major problems in domestic animals and humans. Selection for higher milk production in United States dairy cattle has been very successful during the past 50 years, however the modern lactating dairy cow exhibits a high incidence of subfertility and infertility with a national pregnancy rate of only 15 to 20%. Similarly, pregnancy loss is the most common complication of human gestation, occurring in as many as 75% of all women trying to conceive with losses occurring most frequently in the first two weeks of gestation. Birth rates in humans following transfer of a non-donor in vitro-derived embryo vary depending upon age of the female donor but average only 35%. Pregnancy rates in both natural and assisted reproductive technology (ART)-derived conceptions are largely influenced by embryo quality and endometrial receptivity to implantation. The receptive endometrium represents a temporary, but unique physiological state of the uterus when conceptus (embryo and associated extraembryonic membranes) growth and implantation is possible. Inadequate endometrial receptivity affects conceptus growth, signaling for pregnancy recognition, and compromises implantation. Defects in endometrial receptivity cause pregnancy loss and thus fertility problems in both humans and domestic animals. In order to better understand the biological and genetic mechanisms regulating uterine and conceptus competency for establishment and maintenance of pregnancy, we are using a systems biology approach combined with innovative large animal models. In beef heifers, serial transfer of in vitro-produced embryos has been used to select animals with intrinsic differences in early pregnancy loss. The selected animals are being used in a series of experiments to uncover the physiological and genetic mechanisms governing endometrial receptivity and pregnancy success. In dairy cattle, breeding and production records are used to identify heifers and primiparous lactating cows as well as bulls with inherent differences in fertility based on pregnancy rates. Samples of DNA from the heifers and cows are being subjected to a genome-wide association study (GWAS) that incorporates analyses of both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) to identify genomic loci associated with high and low fertility. In addition, functional SNPs associated with daughter pregnancy rate (DPR) and early embryo development are being identified using semen from genotyped bulls and an in vitro embryo development system. The goal is to develop a genetic test that will enable the accurate ranking of heifers, cows and sires for fertility and, subsequently, enables the reduction of subfertility and infertility through an increased rate of change in genetic selection. This research is expected to provide a better understanding of origins of infertility and pregnancy loss and improve assisted reproduction efficiency in both domestic animals and humans. The research should lead to new therapies to enhance pregnancy outcome in females conceiving naturally or via assisted reproduction technologies (ART) and to diagnose, treat and prevent infertility and recurrent pregnancy loss. This project is supported by Agriculture and Food Research Initiative Competitive Grant no. 2013-68004-20365 from the USDA National Institute of Food and Agriculture and R01HD072898 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development.