A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle.

Polledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at the polled locus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del; Del11) in the second exon of ZEB2 gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product of ZEB2 by almost 91%. Moreover, we showed that all animals carrying Del11 mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations in ZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting only ZEB2 and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly that ZEB2 plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals.

Gene expression in bovine endometrial cells and blood-derived neutrophils stimulated by uterine secretions.

Uterine epithelial cells (UEC) and migrated polymorphonuclear cells (PMN) play important roles in the uterine defence against microbial infection. The aims of the present study were to investigate i) whether undiluted uterine secretions modulate the expression of genes associated with the innate immune response in UEC and PMN in vitro, ii) whether these changes differ between the two cell populations and iii) whether uterine secretions from cows with subclinical endometritis produce a different response to those from unaffected cows. Therefore, undiluted uterine secretions, cytobrush and biopsy samples were collected from bovine uteri at a local abattoir. All cows had calved at least 3 months prior to sample collection. Subclinical endometritis was diagnosed by cytology (≥5% polymorphonuclear neutrophils) and histology. The uteri were thereby retrospectively categorised as endometritis-positive (E-pos; n = 14), if either the cytology or the histology results were positive, or endometritis-negative (E-neg; n = 17), if both diagnostics were negative. Cultured UEC responded to secretions from E-pos and E-neg cows with an increased gene expression of CXC ligand (CXCL) 8 and interleukin (IL) 6 compared to incubation with control medium alone. PMN expressed significantly higher mRNA levels of CXCL5, CXCL8 and IL1B in response to supernatant from UEC incubated with secretions from both groups (E-pos and E-neg) compared to those incubated with control medium alone. Gene expression of IL10 in uterine epithelial cells remained comparable to the control in cells exposed to E-pos secretions and was 3.6 times lower in those exposed to E-neg secretions. These results demonstrate that the expression of genes associated with the innate immune response in UEC and indirectly also PMN is affected by uterine secretions in vitro. Depending on the target gene, these changes differ between the two cell populations. UEC exposed to uterine secretions from cows without subclinical endometritis produce lower levels of IL10 compared to those exposed to secretions from affected cows or control medium alone. Therefore, the model established in this study can be used as a valuable tool to further understand the contributions of the two cell populations to the coordinated immune response in the uterus.

[Uterine torsion in cattle: Treatment, risk of injury for the cow and prognosis for the calf]. / Torsio uteri beim Rind: Therapie sowie Verletzungsrisiko für die Kuh und Prognosestellung für das Kalb.

OBJECTIVE: In cows with uterine torsion, clinical parameters and different treatments were evaluated with regards to their success. The aim of the study was to investigate important factors for diagnosis and prognosis of uterine torsion and their consequences for treatment decisions. MATERIAL AND METHODS: The study presents 114 cases of uterine torsion documented under field conditions. The cows were examined before retorsion of the uterus and immediately post partum. RESULTS: In cases of good maternal preparation for parturition, neonatal mortality was 14.9 %, while in cases of insufficient preparation, this rose to 58.3% (p= 0.006). When uterine torsion lasted > 12 hours, only 34.8 % of the calves survived, while in cases with a duration of ˂ 6 hours or 6-12 hours, 85.7 % and 92.2 % of the calves survived, respectively (p ˂ 0.001). In 82.5 % of the cases, intravaginal manual rotation of the fetus and uterus was performed, while in 17.5 % of the cases, cows were rolled by simultaneously fixating the uterus and fetus with a plank. No statistically significant differences were found between these two treatment types regarding neonatal mortality (4.7 % vs. 18.2 %; p = 0.139) or lacerations of the dam (31.9 % vs. 42.1 %; p = 0.391). A delayed extraction of the calf after successful retorsion and waiting for widening of the cervical canal is an option in cases of insufficient dilatation of the cervical canal, even when there is a significantly higher risk for lacerations of the dam (57.2 %) compared to an immediate extraction (26.8 %; p = 0.018). As the duration of manipulation increases, the extent of injury to the dam also increases significantly (p ˂ 0.001). CONCLUSION AND CLINICAL RELEVANCE: The quality of maternal preparation for parturition in cows with uterine torsion can be used as a prognostic factor for calf survival. Under field conditions, most of the cases of uterine torsion can be successfully treated manually. An appropriate and indication-oriented use of the rolling method with the application of a plank can be recommended. In cases of uterine torsion, proper periparturient monitoring and early intervention are of crucial importance for the course of the disease and for the prognosis of the dam and offspring.