Cysteamine and N-Acetyl-cysteine Alleviate Placental Oxidative Stress and Barrier Function Damage Induced by Deoxynivalenol

Abstract

Sows are highly sensitive to deoxynivalenol (DON) and susceptible to reproductive toxicity caused by oxidative stress, but the potential mechanisms and effective interventions remain unclear. Here, we investigated the role of two antioxidants (cysteamine and N-acetyl-cysteine) in regulating the reproductive performance, redox status, and placental barrier function of sows and their potential mechanisms under DON exposure. Maternal dietary supply of antioxidants from day 85 of gestation to parturition reduced the incidence of stillbirths and low-birth-weight piglets under DON exposure. Moreover, the alleviation of DON-induced reproductive toxicity by dietary antioxidants was associated with the alleviation of placental oxidative stress, the enhancement of the placental barrier, and the vascular function of sows. Furthermore, in vivo and in vitro vascularized placental barrier modeling further demonstrated that antioxidants could reverse both DON transport across the placenta and DON-induced increase of placental barrier permeability. The molecular mechanism of antioxidant resistance to DON toxicity may be related to the signal transducer and activator of the transcription-3-occludin/zonula occludens-1 signaling pathway. Collectively, these results demonstrate the potential of antioxidants to protect the mother from DON-induced reproductive toxicity by alleviating placental oxidative stress and enhancing the placental barrier.

Retinoic Acid–PPARα Mediates β-Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol

“…Generally, the distribution of DON was related to the target organ damage, so we further measured DON levels in different tissues of mice and found that DON was highly enriched in the placenta, and it was also detected in fetal tissues. This was consistent with the previous results of DON in different species, , suggesting that DON could be transported from the maternal side to the fetal side through the placenta, ultimately affecting fetal development. The DON-caused adverse pregnancy outcomes and embryotoxicity can be inferred to be related to placental function impairment.…”

“…In the current study, DON-induced adverse pregnancy outcomes and embryonic development impairment were in line with other and our previous studies, indicating that DON could induce embryotoxicity and reproductive toxicity. , Compared with previous studies, the present experiment examined placental efficiency and the IUGR rate. Notably, placental efficiency, the grams of fetus produced per gram of placenta, was originally studied between swine breeds as a key factor in efficient nutrient exchange .…”

“…Notably, placental efficiency, the grams of fetus produced per gram of placenta, was originally studied between swine breeds as a key factor in efficient nutrient exchange . Placental efficiency was reported to have a significant positive correlation with fetal weight . In this study, the lower placental efficiency caused by DON exposure was accompanied by a higher IUGR rate, possibly due to the decreased ability of the placenta to deliver effective nutrients to the fetus .…”

“…Specifically, DON was detected in fetal serum, liver, bile, and urine samples after feeding pregnant sows DON-contaminated diets during pregnancy. , Additionally, the exposure of pregnant mice to DON could impair fetal development and cause skeletal malformations . Moreover, the adverse effects of DON exposure were also verified in vitro through the placental perfusions system and trans-well coculture model . However, few studies have been performed on the toxicity of DON to placental function and the related mechanism, and the effective interventions are still unclear.…”