Influence of Maternal Nutrition and One-Carbon Metabolites Supplementation during Early Pregnancy on Bovine Fetal Small Intestine Vascularity and Cell Proliferation

Simple Summary Maternal nutrition during gestation can have profound effects on fetal growth and development. Perturbations to maternal nutrition during this period can predispose to adverse health and productivity outcomes in postnatal life. A biochemical pathway present in cells that can be affected by limited maternal nutrition is one-carbon metabolism. This pathway is related to epigenetics, which regulates gene expression or the turning on and off genes. The one-carbon metabolites (OCM) folate, vitamin B12, methionine, and choline are important compounds in this pathway. Our research aimed to evaluate the effect of maternal nutrition during early pregnancy on fetal intestinal characteristics and assess if OCM supplementation could mitigate changes due to altered maternal nutrition. We discovered that OCM supplementation in nutrition-restricted dams enhanced vascularity development signaling, decreased small intestinal weight, and optimized intestinal cell growth, potentially helping the fetus adapt to a lower nutrient supply.Abstract To investigate the effects of nutrient restriction and one-carbon metabolite (OCM) supplementation (folate, vitamin B12, methionine, and choline) on fetal small intestine weight, vascularity, and cell proliferation, 29 (n = 7 +/- 1 per treatment) crossbred Angus beef heifers (436 +/- 42 kg) were estrous synchronized and conceived by artificial insemination with female sexed semen from a single sire. Then, they were allotted randomly to one of four treatments in a 2 x 2 factorial arrangement with the main factors of nutritional plane [control (CON) vs. restricted feed intake (RES)] and OCM supplementation [without OCM (-OCM) or with OCM (+OCM)]. Heifers receiving the CON level of intake were fed to target an average daily gain of 0.45 kg/day, which would allow them to reach 80% of mature BW by calving. Heifers receiving the RES level of intake were fed to lose 0.23 kg/heifer daily, which mimics observed production responses in heifers that experience a diet and environment change during early gestation. Targeted heifer gain and OCM treatments were administered from d 0 to 63 of gestation, and then all heifers were fed a common diet targeting 0.45 kg/d gain until d 161 of gestation, when heifers were slaughtered, and fetal jejunum was collected. Gain had no effect (p = 0.17) on the fetal small intestinal weight. However, OCM treatments (p = 0.02) displayed less weight compared to the -OCM groups. Capillary area density was increased in fetal jejunal villi of RES - OCM (p = 0.02). Vascular endothelial growth factor receptor 2 (VEGFR2) positivity ratio tended to be greater (p = 0.08) in villi and was less in the crypts (p = 0.02) of the RES + OCM group. Cell proliferation decreased (p = 0.02) in villi and crypts of fetal jejunal tissue from heifers fed the RES + OCM treatment compared with all groups and CON - OCM, respectively. Spatial cell density increased in RES - OCM compared with CON + OCM (p = 0.05). Combined, these data show OCM supplementation can increase expression of VEGFR2 in jejunal villi, which will promote maintenance of the microvascular beds, while at the same time decreasing small intestine weight and crypt cell proliferation.