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ARS Home » Plains Area » Miles City, Montana » Livestock and Range Research Laboratory » Research » Publications at this Location » Publication #322324
Title: Systems biology approach to understanding uterine receptivity and pregnancy loss

Author
item BURNS, GREGORY - Washington State University
item WEHRMAN, MICHAEL - Washington State University
item Geary, Thomas
item MOSS, JAMES - University Of Florida
item DENICOL, ANNA - University Of Florida
item DOBBS, KYLE - University Of Florida
item ORTEGA, M - University Of Florida
item HANSEN, PETER - University Of Florida
item WOJTOWICZ, ANDREZJ - Washington State University
item NEIBERGS, HOLLY - Washington State University
item SPENCER, THOMAS - Washington State University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/19/2015
Publication Date: 6/18/2015
Citation: Burns, G.W., Wehrman, M.E., Geary, T.W., Moss, J.I., Denicol, A.C., Dobbs, K.B., Ortega, M.S., Hansen, P.J., Wojtowicz, A., Neibergs, H., Spencer, T.E. 2015. Systems biology approach to understanding uterine receptivity and pregnancy loss. Society for Study of Reproduction Meeting Abstract. CD.

Interpretive Summary:

Technical Abstract: Infertility and subfertility represent major problems in domestic animals and humans. The majority of embryonic loss in those species occurs during the first month of gestation when pregnancy recognition and conceptus (embryo and associated extraembryonic membranes) implantation are obligatory. The endometrium in ruminants represents a temporary, but unique physiological state of receptivity when conceptus elongation and implantation is possible. Thus, inadequate uterine receptivity may compromise conceptus growth, signaling for pregnancy recognition, and pregnancy establishment. However, the critical genes and physiological pathways that mediate uterine receptivity and pregnancy success are not well understood. Predominantly Angus heifers (n=270) were classified based on fertility using serial ET (n=4 rounds) to select animals with intrinsic differences in pregnancy loss. In each round, a single in vitro-produced embryo of high quality was transferred into synchronized heifers (n=228), and pregnancy determined on day 28 by ultrasound. Heifers were then classified as high fertile (HF; 100% pregnancy success) or subfertile (SF; =25% pregnancy success). Following fertility classification, a single in vivo-produced embryo was transferred into HF (n=29) and SF (n=32) heifers on day 7 post-estrus. Uteri of all recipient heifers were flushed on day 14 to recover the conceptus. If present, the recovered conceptus was imaged on a Zeiss Discovery V8 stereomicroscope with an AxioCam ICc 1 and AxioVision version 4.6 software. Conceptus length and area was then determined using ImageJ (NIH, version 1.48). The effect of recipient fertility classification on conception rate and conceptus length and area were determined using embryo donor as a covariate. Conception rate was not different (P=0.93) in HF (64%) and SF (56%) heifers. Conceptus length was not different (P>0.10) between HF (3.0 ± 1.7 mm) and SF (5.0 ± 1.62 mm) heifers. Conceptus area was also not different (P>0.10) between HF (3.68 ± 1.74 mm2) and SF (4.99 ± 1.81 mm2) heifers. The HF and SF heifers were genotyped with the Illumina 778K SNP BovineHD Genotyping BeadChip. A genome-wide association study (GWAS) was then conducted using the EMMAX mixed-model association test. Highly significant associations (n=20; P<5X10-7) were detected on several chromosomes (BTA 2, 3, 4, 5, 6, 8, 13, 15, 16, 30) and queried against the cattle Quantitative Trait Loci (QTL) database which revealed 8 SNPs located in loci with at least one known fertility trait. Results of these studies indicate that pre-implantation conceptus growth is not compromised in SF heifers that are fertility-classified by ET. Further, they support the idea that the observed difference in capacity for pregnancy success is manifested between days 14 and 28 when pregnancy recognition signaling and conceptus implantation must succeed for the establishment of pregnancy. The genetic markers identified in this study may be useful to select animals for fertility and enhance our understanding of the physiological pathways governing pregnancy success and loss in mammals. Supported by 1 R01 HD072898 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.