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

Abstract

In vitro production (IVP) of embryos in cattle can result in large/abnormal offspring syndrome (LOS/AOS) which is characterized by macrosomia. LOS can cause dystocia and lead to the death of dam and calf. Currently, no test exists to identify LOS pregnancies. We hypothesized that fetal ultrasonography and/or maternal blood markers are useful to identify LOS. Bovine fetuses were generated by artificial insemination (control) or IVP. Fetal ultrasonographies were taken on gestation D55 (D55) and fetal collections performed on D56 or D105 (gestation in cattle ≈ D280). IVP fetuses weighing ≥ 97 percentile of the control weight were considered LOS. Ultrasonography results show that the product of six D55 measurements can be used to identify extreme cases of LOS. To determine whether maternal blood can be used to identify LOS, leukocyte mRNA from 23 females was sequenced. Unsupervised hierarchical clustering grouped the transcriptomes of the two females carrying the two largest LOS fetuses. Comparison of the leukocyte transcriptomes of these two females to the transcriptome of all other females identified several misregulated transcripts on gestation D55 and D105 with LOC783838 and PCDH1 being misregulated at both time-points. Together our data suggest that LOS is identifiable during pregnancy in cattle.

Maternal blood transcriptome as a sensor of fetal organ maturation at the end of organogenesis in cattle

“…The maternal metabolome can be employed in mares to predict gestational age [59]. In cattle, circulating microRNAs in the maternal plasma differ according to the fetal sex at 39 days of gestation [60], and oversized fetuses induce changes in the maternal blood transcriptome at 55 and 105 days of gestation [61]. Here, we linked the information from the fetal heart and maternal blood to accurately predict fetal weight in 42-day fetuses.…”

25 years after Dolly: Update on long‐term effects of embryo biotechnologies

“…As animals are generally culled at a few years of age, only clinically visible effects observed in young animals are reported. To date, and since the removal of serum and co‐culture from embryo culture conditions that were shown to be related to the occurrence of LOS, adverse neonatal and adult health outcomes associated with IVP embryos are not much reported by the bovine industry, although an increase in birth weight is still observed (Hansen, 2020; Rivera et al, 2022), associated with high levels of morbidity and mortality among IVP embryo‐derived ruminant offspring (Bonilla et al, 2014; Rivera, 2020; Sinclair et al, 2000). Commonly observed phenomena include increases in placenta, body and organ size, perturbations in growth rate, cardiovascular function and glucose homeostasis regulation (Hansen & Siqueira, 2017).…”

“…The worldwide production of IVP embryos is, however, increasing rapidly, with more than 1.1 million bovine embryos being produced in vitro yearly (Viana, 2021). Recently, informal reports on the birth of IVP bovine offspring with gestational abnormalities, such as increased size offspring and large placentas, have become more common, prompting recent research on the prenatal diagnosis (Rivera et al, 2022) and epigenetic aetiology (Rivera, 2020) of the syndrome in bovine. Thus, it is appropriate to consider to which extent pre‐ and post‐natal survival, health and well‐being are affected in IVP‐derived livestock embryos.…”

Analysis of histone H3K4me3 modifications in bovine placenta derived from different calf‐production methods

“…In LOS foetuses, other abnormal phenotypes are often observed such as visceromegaly, enlarged tongue (macroglossia), umbilical hernia, ear malformation, hemihyperplasia (asymmetric growth), brain haemorrhage, abdominal ascites and abdominal wall defect. Foetal abnormalities due to LOS can adversely affect both mother and foetus, including delivery difficulties due to foetal overweight and suckling and breathing failure of the newborn (Chen et al, 2013;Hiendleder et al, 2006;Rivera et al, 2022). The aetiology of LOS is not clearly understood, but abnormal epigenetic modifications caused by environmental factors during early embryonic period are suspected (Chen et al, 2015(Chen et al, , 2017.…”