Abstract
Simple SummaryThe present study aimed to determine the blood concentrations of L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine, modulating nitric oxide (NO) synthesis, in single, twin. and triplet pregnancies in ewes undergoing either dietary energy restriction or receiving 100% of their energy requirements. Blood concentrations of L-arginine, of its metabolites. and the ratio between NO synthesis boosters and inhibitors are altered in energy-restricted ewes, these alterations being higher in ewes carrying multiple fetuses.The aim of this study was to investigate the blood concentrations of L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine, which are regulators of nitric oxide (NO) synthesis, in single, twin, and triplet pregnancies in ewes undergoing either a dietary energy restriction or receiving 100% of their energy requirements. From day 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates fulfilling either 100% of ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 12 twin pregnancies, and 4 triplet pregnancies) or only 45% (feed-restricted group; n = 29; 11 singleton pregnancies, 15 twin pregnancies, and 3 triplet pregnancies). Blood samples were collected monthly to measure, by capillary electrophoresis, the circulating concentrations of arginine, ADMA, homoarginine, SDMA, and of other amino acids not involved in NO synthesis to rule out possible direct effects of diet restriction on their concentrations. No differences between groups were observed in the circulating concentrations of most of the amino acids investigated. L-homoarginine increased markedly in both groups during pregnancy (p < 0.001). SDMA (p < 0.01), L-arginine, and ADMA concentrations were higher in feed-restricted ewes than in controls. The L-arginine/ADMA ratio, an indicator of NO production by NOS, decreased towards term without differences between groups. The ADMA/SDMA ratio, an index of the ADMA degrading enzyme activity, was higher in controls than in feed-restricted ewes (p < 0.001). Obtained results show that circulating concentrations of L-arginine, of its metabolites, and the ratio between NO synthesis boosters and inhibitors are altered in energy-restricted ewes, and that these alterations are more marked in ewes carrying multiple fetuses.
Highlights
Nitric oxide (NO) is a key regulator of fetal homeostasis during pregnancy and it is considered the main vasodilator agent in the placenta, facilitating the maternal cardio-vascular changes, fetal development, and growth [1]
No difference was found in live weight of ewes carrying triplets between the two experimental groups
Delivery of singleton lambs occurred one day after in feed-restricted ewes compared to controls (p < 0.05), while no differences were observed in the duration of twin and triplet pregnancies between the two groups (Table 2)
Summary
Nitric oxide (NO) is a key regulator of fetal homeostasis during pregnancy and it is considered the main vasodilator agent in the placenta, facilitating the maternal cardio-vascular changes, fetal development, and growth [1]. It has been identified in the syncytiotrophoblast and the fetoplacental vascular endothelium of mice where it contributes to lower fetoplacental vascular resistance and modulates other trophoblast functions such as implantation, differentiation, motility, invasion, and apoptosis [2]. The L-arginine-ADMA axis strictly controls the production of NO in numerous physiological and pathological conditions, including pregnancy. The L-arginine to ADMA ratio can be used to assess altered NOS activity due to alterations of this axis [5]
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