Effects of n-acetyl-cysteine supplementation in late gestational diet on maternal-placental redox status, placental NLRP3 inflammasome, and fecal microbiota in sows1

J Anim Sci. 2019 Apr 3;97(4):1757-1771. doi: 10.1093/jas/skz058.


Although n-acetyl-cysteine (NAC) has been shown to efficiently alleviate oxidative stress, inflammatory response, and alter gut microbiota, little attention has been focused on their interactions with placental metabolic status of sows. The effects of NAC on the placental redox status, function, inflammasome, and fecal microbiota in sows were explored to clarify the correlation between the fecal microbiota and placenta. Sows were divided into either the control group or the NAC group which received dietary 0.5% NAC supplementation from day 85 of gestation to delivery. Plasma redox status, placental growth factors, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome, fecal microbial metabolites, and communities were evaluated. Compared with the control group, although NAC did not ameliorate reproductive performance of sows (P > 0.05), it significantly improved maternal-placental health, which was accompanied by increased activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), decreased level of malondialdehyde (MDA), and lowered expression of interleukin (IL)-1β and IL-18 through inhibiting NLRP3 inflammasome (P < 0.05). Additionally, NAC significantly increased placental insulin-like growth factors (IGFs) and E-cadherin contents (P < 0.05), elevated the expression of genes involved in angiogenesis and amino acids transporters (P < 0.05), and decreased the microtubule-associated protein light chain 3B (LC3B) and Beclin-1 protein expression (P < 0.05). Furthermore, NAC increased the relative abundances of fecal Prevotella, Clostridium cluster XIVa, and Roseburial/Eubacterium rectale (P < 0.05), which were negatively correlated with placental NLRP3 and positively with solute carrier family 7, member 8 (Slc7a8; P < 0.05). In conclusion, NAC supplementation during late gestation alleviated maternal-placental oxidative stress and inflammatory response, improved placental function, and altered fecal microbial communities.

Keywords: fecal microbiota; n-acetyl-cysteine; nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3; placenta; sows.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Diet / veterinary
  • Dietary Supplements*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Glutathione Peroxidase / metabolism
  • Inflammasomes / drug effects
  • Malondialdehyde / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / drug effects
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Placenta / drug effects
  • Placenta / metabolism
  • Pregnancy
  • Reproduction / drug effects*
  • Superoxide Dismutase / metabolism
  • Swine / physiology*


  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Malondialdehyde
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Acetylcysteine