Identification of large offspring syndrome during pregnancy through maternal blood transcriptome analyses

In vitro production of bovine embryos can result in large/abnormal offspring syndrome (LOS), a condition characterized by macrosomia, macroglossia, exomphalos and placental abnormalities. LOS can lead to the death of dam and calf. Currently, no test exists to identify LOS pregnancies. We hypothesized that maternal blood markers are useful to identify LOS. Bovine fetuses were generated by artificial insemination (control) or produced in vitro. Surgical fetal collections performed on d56 or d105. Maternal blood was collected on gestation d55 and d105. On d56 and d105, fetuses produced in vitro weighing greater than 97th percentile of the AI weight were considered as LOS. To determine whether maternal blood may be used to identify LOS on d55 and/or d105 of gestation, leukocyte mRNA from 23 pregnant females was isolated and sequenced using a short-read platform. Unsupervised clustering grouped 20 samples by animal (n=10 heifers) rather than by stage of pregnancy. Leukocyte gene expression analyses revealed >3,500 differentially expressed genes in females carrying the two largest LOS fetuses. In summary, our study suggests that transcript amount of ATF7IP from d105 maternal leukocytes may be useful to identify extreme cases of LOS. Overall design: Comparision of day 55 and day 105 maternal blood transcriptome analyses of females carrying day 105 the AI, ART-normal and ART-LOS fetuses.