Dihydrotestosterone mediates the inflammation effect under lipopolysaccharides in bovine endometrial epithelial cells via AR blockading TLR4/MyD88 signaling pathway

Anim Reprod Sci. 2023 Aug:255:107292. doi: 10.1016/j.anireprosci.2023.107292. Epub 2023 Jun 29.

Abstract

Dihydrotestosterone (DHT) is a potent nonaromatizable 5α-reduced androgen with both positive and negative effect on inflammation process. However, it remains unknown whether DHT can regulate Lipopolysaccharides (LPS)-induced inflammation in bovine endometrial epithelial cells (bEECs). Here, we demonstrated that the DHT biosynthesis ability and androgen receptors (AR) expression is defective in bovine endometrial with endometritis, which aggravates endometrial inflammation. In vitro study, we established a LPS-induced inflammation model in bEECs, and found that DHT inhibited the TLR4 and MyD88 protein as well as TNF-α, IL-1β, and IL-6 mRNA of bEECs in a dose-dependent manner. Moreover, the anti-inflammation effect of DHT was blocked by AR inhibitor flutamide. Together, we demonstrated that supplementing DHT can alleviate the inflammation response of bEECs caused by LPS, which is associated with AR regulating the inhibition of TLR4/MyD88 signaling pathway.

Keywords: Bovine endometrial epithelial cells (bEECs); Dihydrotestosterone; Inflammatory factors; TLR4/MyD88 signaling.

MeSH terms

  • Animals
  • Cattle
  • Cattle Diseases* / metabolism
  • Dihydrotestosterone / metabolism
  • Dihydrotestosterone / pharmacology
  • Endometritis* / chemically induced
  • Endometritis* / metabolism
  • Endometritis* / veterinary
  • Epithelial Cells
  • Female
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / veterinary
  • Lipopolysaccharides / toxicity
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Myeloid Differentiation Factor 88 / pharmacology
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Lipopolysaccharides
  • Dihydrotestosterone
  • Receptors, Androgen
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptor 4