The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level.

This study aimed to investigate the anticancer effects of salidroside (SAL), and its inhibitory effects on the proliferation and apoptosis of SKOV3 cells, and its regulatory activities on the carcinogenesis, progression, and growth of ovarian cancer in a mouse model. The expression levels of ARID1A, PTEN, TGF-β, SMAD, FSHR, and ER-β genes and proteins in SKOV3 cells were detected and analyzed. A total of 125 female mice were used to establish ovarian cancer models, which were randomly divided into the control group (CG), Test-1 group, Test-2 group, and Test-3 group. During the experiment, the tumor volume and multiple related indicators in the ascites and serum of mice were dynamically measured. The results showed that the proliferation inhibition rate of SKOV3 cells in the SAL-treated groups was significantly increased as compared with CG. The average daily tumor growth rate of the Test-1, Test-2, and Test-3 groups was lower than that of the CG. On day 50, the p53 gene expression levels in the Test-1, Test-2, and Test-3 groups were increased by 103.77%, 150.94%, and 124.53%, respectively, relative to the CG. The ovarian cancer cells were found in tissue sections at day 14. The contents of CA125 and VEGF-A in the ascites of the SAL-treated groups were higher than those in the C. However, the increments were gradually reduced with the increase in SAL dosage in a concentration-dependent manner. On day 50, the counts of Treg cells in the Test-2 and Test-3 groups were increased by 14.39% and 30.14% compared with the Ctrl group. Additionally, the concentrations of IL-2, IL-10, and TGF-β in the Test-3 group were increased by 271.56%, 663.69% and 557.58%, respectively. In conclusion, this study is the first time to reveal that salidroside can inhibit the proliferation of SKOV3 cells by promoting their apoptosis. It can suppress the carcinogenesis, progression, and growth of ovarian cancer by upregulating the expression of PTEN, ARID1A, TGF-β, and SMAD4, increasing the production of CA125, VEGF-A, IL-2, and IL-10, and elevating the levels of CD3⁺, CD8⁺, and Treg cells in the ascites. SAL at a dose of 400 μg/g exhibited the most potent inhibitory effect on ovarian cancer, which lays a solid foundation for the development of salidroside as a novel anticancer drug.