Maternal Supply of Cysteamine during Late Gestation Alleviates Oxidative Stress and Enhances Angiogenesis in Porcine Placenta

Abstract

Background: Oxidative stress in placenta is associated with the occurrence of adverse pregnancy outcomes in sow, but there are few satisfactory treatment strategies for these conditions. This study investigated the potential of cysteamine (CS) as an antioxidant protectant for regulating the reproductive performance, redox status, and placental angiogenesis of sows.Methods: The placental oxidative stress status and vascular density of piglets with different birth weights: <1.0 kg (low birth weight, LBW) and 1.4-1.6 kg (normal birth weight, NBW) were evaluated, followed by allotting 84 sows to four treatments (n=21) and feeding them with a basal diet supplemented with 0, 100, 300, or 500 mg/kg of CS (CON, CS100, CS300, and CS500 diet) from day 85 of gestation to day 21 of lactation, respectively. Placentae, serum and colostrum, and blood samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, the in vivo results were validated using porcine vascular endothelial cells (PVECs).Results: The placentae for the LBW piglets had higher oxidative damage and lower vascular density than those for the NBW piglets (P < 0.05). Further experiments with sows showed that compared with the CON group, the CS100 group was lower in the stillbirth and invalid rates, and higher in the piglet birth weight and placental efficiency (P < 0.05). Meanwhile, the CS100 group also displayed higher glutathione and lower malondialdehyde in both the serum and colostrum of sows (P < 0.05). Interestingly, compared to the CON group, the LBW placentae of the CS100 group showed a decrease in oxidative damage, while an increase in vascular density (P < 0.05), as well as the mRNA level of vascular endothelial growth factor A and the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (P < 0.05). Furthermore, the in vitro experiment indicated that CS pre-treatment could significantly reverse the NADPH oxidase 2-ROS-mediated inactivation of signal transducer and activator of transcription-3 (Stat3) signaling pathway induced by H2O2 inhibition of the proliferation, tube formation, and migration of PVECs (P < 0.05).Conclusions: The results indicated that oxidative stress and impaired angiogenesis might contribute to the occurrence of low-birth-weight piglets during pregnancy, but CS supplementation at 100 mg/kg during late gestation and lactation of sows could alleviate oxidative stress and enhance angiogenesis in placenta, thereby improving pregnancy outcome. The in vitro data showed that the underlying mechanism for the positive effects of CS may be related to the activation of Stat3.

Effect of Maternal Catalase Supplementation on Reproductive Performance, Antioxidant Activity and Mineral Transport in Sows and Piglets

“…In addition, the rapid development of the fetuses during late gestation may squeeze the digestive tract and cause gastrointestinal dysfunction of sows [ 34 ], resulting in elevated systemic oxidative stress. These processes induce sows to produce large amounts of free radicals, resulting in placental dysfunction and fetal growth retardation [ 35 ]. Furthermore, the swine intestinal tract is a major target organ of free radical attack, which causes intestinal structure destruction, microbial disturbance, and nutrient absorption obstacles [ 36 ].…”

UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model

“…Placenta, a combination of the fetus and the mother, is an important guarantee for the fetus to obtain maternal nutrition ( 11 ). Placental angiogenesis is critical to the development and survival of fetal pigs ( 31 ). The density of blood vessels in the placenta of Tibetan sows was shown to increase with the progress of gestation in our recent study (unpublished data).…”

A review of the amino acid metabolism in placental function response to fetal loss and low birth weight in pigs

“…Among the nutrients required by pregnant sows, amino acids play the most important role in placental growth due to their involvement in the synthesis of sufficient proteins to support the proliferation of trophectoderm and endothelial cells [10]. Amino acids are not only the building blocks of proteins in cells, but also precursors for synthesis of nitrogenous substances (e.g., nitric oxide (NO), polyamines, and glutathione) essential for placental growth and angiogenesis, conceptus development or scavenging free radicals to prevent placental oxidative damage [10,44,45]. As mentioned earlier, the placental demand of amino acids varies markedly with the extension of gestation, so the supply of amino acids to the placenta must be controlled to ensure an adequate supply of each amino acid.…”