Mense Kirsten, Heidekorn-Dettmer Julia, Wirthgen Elisa, Brockelmann Yette, Bortfeldt Ralf, Peter Sarah, Jung Markus, Höflich Christine, Hoeflich Andreas, Schmicke Marion
Institute for the Reproduction of Farm Animals Schoenow, Bernau, Germany.
Clinic for Cattle, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Front Endocrinol (Lausanne). 2018 Jun 12;9:310. doi: 10.3389/fendo.2018.00310. eCollection 2018.
Insulin-like growth factors (IGFs) play a critical role in fetal growth, and components of the IGF system have been associated with fetal growth restriction in women. In human pregnancy, the proteolytic cleavage of insulin-like growth factor binding proteins (IGFBPs), particularly IGFBP-4, releases free IGF for respective action at the tissue level. The aim of the present study was to determine IGFBP-2, IGFBP-3, and IGFBP-4 concentrations by Western ligand blotting during pregnancy until day 100 in cows and to compare these concentrations with those of non-pregnant cows and cows undergoing embryonic/fetal mortality. Therefore, two study trials (I and II) and an study were conducted. In study I, 43 cows were not pregnant, 34 cows were pregnant, and 4 cows were undergoing fm. In study II, 500 cows were examined, and 7 cases of pregnancy loss between days 24-27 and 34-37 after artificial insemination (AI, late embryonic mortality; em) and 8 cases of pregnancy loss between days 34-37 and 54-57 after AI (late embryonic mortality and early fetal mortality; em/fm) were defined from the analyses of 30 pregnant and 20 non-pregnant cows randomly selected for insulin-like growth factor 1 and IGFBP analyses. serum from pregnant ( = 3) and non-pregnant ( = 3) cows spiked after incubation with recombinant human (rh) IGFBP-4 for 24 h, and IGFBP-4 levels were analyzed before and after incubation to detect proteolytic degradation. The IGFBP-2, -3, and -4 concentrations did not decline during early pregnancy in cows, while IGFBP-4 concentrations were comparable between pregnant and non-pregnant cows, irrespective of low proteolytic activity, which was also demonstrated in cows. Interestingly, cows with em or fm showed distinct IGFBP patterns. The IGFBP-2 and -3 concentrations were higher ( < 0.05) in cows with fm compared to pregnant. The IGFBP-4 levels were significantly higher in cows developing fm. Thus, distinct differences in the circulating IGFBP concentrations could be associated with late embryonic and early fetal losses in cattle.
胰岛素样生长因子（IGFs）在胎儿生长中起关键作用，IGF系统的组成部分与女性胎儿生长受限有关。在人类妊娠中，胰岛素样生长因子结合蛋白（IGFBPs），特别是IGFBP - 4的蛋白水解裂解会释放游离IGF，使其在组织水平发挥各自的作用。本研究的目的是通过Western配体印迹法测定奶牛妊娠至第100天时IGFBP - 2、IGFBP - 3和IGFBP - 4的浓度，并将这些浓度与未怀孕奶牛以及经历胚胎/胎儿死亡的奶牛的浓度进行比较。因此，进行了两项研究试验（I和II）以及一项研究。在研究I中，43头奶牛未怀孕，34头奶牛怀孕，4头奶牛正在经历胚胎/胎儿死亡。在研究II中，检查了500头奶牛，从随机选择进行胰岛素样生长因子1和IGFBP分析的30头怀孕奶牛和20头未怀孕奶牛的分析中确定了7例人工授精（AI）后第24 - 27天和34 - 37天之间的妊娠丢失（晚期胚胎死亡；em）以及8例AI后第34 - 37天和54 - 57天之间的妊娠丢失（晚期胚胎死亡和早期胎儿死亡；em/fm）。将重组人（rh）IGFBP - 4与怀孕（n = 3）和未怀孕（n = 3）奶牛的血清孵育24小时后加样，在孵育前后分析IGFBP - 4水平以检测蛋白水解降解。奶牛在妊娠早期IGFBP - 2、- 3和 - 4的浓度没有下降，而无论蛋白水解活性如何，怀孕奶牛和未怀孕奶牛之间的IGFBP - 4浓度相当，这在奶牛中也得到了证实。有趣的是，经历em或fm的奶牛表现出不同的IGFBP模式。与怀孕奶牛相比，经历fm的奶牛中IGFBP - 2和 - 3的浓度更高（P < 0.05）。发生fm的奶牛中IGFBP - 4水平显著更高。因此，循环中IGFBP浓度的明显差异可能与牛的晚期胚胎和早期胎儿丢失有关。
