Abstract

Melatonin (MT) is a bio-antioxidant that has been widely used to prevent pregnancy complications, such as pre-eclampsia and IUGR during gestation. This experiment evaluated the impacts of dietary MT supplementation during pregnancy on reproductive performance, maternal–placental–fetal redox status, placental inflammatory response, and mitochondrial function, and sought a possible underlying mechanism in the placenta. Sixteen fifth parity sows were divided into two groups and fed each day of the gestation period either a control diet or a diet that was the same but for 36 mg of MT. The results showed that dietary supplementation with MT increased placental weight, while the percentage of piglets born with weight < 900 g decreased. Meanwhile, serum and placental MT levels, maternal–placental–fetal redox status, and placental inflammatory response were increased by MT. In addition, dietary MT markedly increased the mRNA levels of nutrient transporters and antioxidant-related genes involved in the Nrf2/ARE pathway in the placenta. Furthermore, dietary MT significantly increased ATP and NAD+ levels, relative mtDNA content, and the protein expression of Sirt1 in the placenta. These results suggested that MT supplementation during gestation could improve maternal–placental–fetal redox status and reproductive performance by ameliorating placental antioxidant status, inflammatory response, and mitochondrial dysfunction.

Highlights

  • Rapid fetal growth during pregnancy leads to increased metabolic burdens on pregnant women or dams, causing elevated systemic oxidative stress [1,2]

  • The current study was carried out to verify the above hypotheses by evaluating the effects of MT on the reproductive performance, maternal–placental–fetal redox status, placental inflammatory response, and mitochondrial function

  • Maternal MT supplementation reduced (p < 0.05) the percentage of piglets born alive with weight < 900 g compared with the control diet (CON)

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Summary

Introduction

Rapid fetal growth during pregnancy leads to increased metabolic burdens on pregnant women or dams, causing elevated systemic oxidative stress [1,2]. MT has been shown to improve fetal growth by increasing uteroplacental blood flow and/or its antioxidant and anti-inflammatory effects, its underlying molecular mechanisms in placental growth and function have rarely been investigated. A previous report has found that maternal oxidative stress is closely related to placental mitochondrial dysfunction [19]. No data are available currently regarding the effects of dietary MT supplementation during gestation on the reproductive performance and antioxidants status of sows, despite the fact that sows are increasingly used as animal models in biomedical researches on human pregnancy because of their similarity in terms of metabolic, inflammatory, gastrointestinal, and cardiovascular features [21]. The current study was carried out to verify the above hypotheses by evaluating the effects of MT on the reproductive performance, maternal–placental–fetal redox status, placental inflammatory response, and mitochondrial function

Animals and Diet Design
Blood Sample Collection
Tissue Sample Collection
Analysis of Oxidative Stress Parameters in Serum and Placenta
Hormonal and Biochemical Parameters Analysis
Measurement of Mitochondrial Respiratory Chain Complex Activities
2.10. Measurement of Inflammatory Cytokine in Placenta
2.11. RNA Extraction and Gene Expression Analysis
2.12. Western Blot Analysis
2.13. Statistical Analysis
Reproductive Performance
Hormonal and Biochemical Parameters in Serum and Placenta
Effects of maternal
Antioxidant Capacity in Serum of Sows and New-Born Piglets
Placental ATP Levels and Mitochondrial Function
Nrf2-Regulated Gene Expression in the Placenta
Maternal
3.10. Nutrient Transporter Gene Expression in Placenta
Discussion
Conclusions
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