Tauroursodeoxycholic acid (TUDCA) enhanced intracytoplasmic sperm injection (ICSI) embryo developmental competence by ameliorating endoplasmic reticulum (ER) stress and inhibiting apoptosis

J Assist Reprod Genet. 2020 Jan;37(1):119-126. doi: 10.1007/s10815-019-01627-2. Epub 2019 Dec 4.

Abstract

Purpose: The objective of this study was to examine the effect of tauroursodeoxycholic acid (TUDCA) on intracytoplasmic sperm injection (ICSI) embryos by evaluating endoplasmic reticulum (ER) stress, apoptosis, and embryo developmental competence in vitro and in vivo.

Methods: ER stress-associated genes and apoptosis-associated genes were measured and apoptosis index was analyzed. Embryo developmental competence was assessed in vitro and in vivo via the inner cell mass (ICM)/trophectoderm (TE) index, pregnancy and implantation rates, and birth rate.

Results: The relative mRNA and protein expression of binding immunoglobulin protein (BIP) was significantly higher in the ICSI embryo group without TUDCA treatment (ICSI-C) than in the in vitro fertilization (IVF) group and in the ICSI embryo group with TUDCA treatment (200 μM) (ICSI-T), while TUDCA ameliorated ER stress in ICSI embryos. Embryos in the ICSI-C group showed a higher apoptosis index than those in the IVF group and ICSI-T group, and there was no significant difference between the IVF group and ICSI-T group. TUDCA can significantly improve ICSI embryo developmental competence in vitro and in vivo based on the ICM/TE index, pregnancy and implantation rates, and birth rate.

Conclusion: ICSI embryos manifested high ER stress and high apoptosis, while TUDCA ameliorated ER stress and reduced apoptosis in ICSI embryos. TUDCA can significantly improve the developmental competence of ICSI embryos in vitro and in vivo. This study provides a new idea for improving the efficiency of ICSI, and it will also have a positive effect on the development of assisted reproduction technologies for humans and other animals.

Keywords: Apoptosis; ER stress; ICSI; Tauroursodeoxycholic acid.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Birth Rate
  • Cholagogues and Choleretics / pharmacology
  • Embryo Implantation
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / drug effects*
  • Embryonic Development / drug effects*
  • Endoplasmic Reticulum Stress / drug effects*
  • Female
  • Fertilization in Vitro / statistics & numerical data*
  • Male
  • Mice, Inbred C57BL
  • Oocytes / drug effects
  • Oocytes / growth & development
  • Pregnancy
  • Pregnancy Rate
  • Reproductive Techniques, Assisted / statistics & numerical data
  • Sperm Injections, Intracytoplasmic / statistics & numerical data*
  • Taurochenodeoxycholic Acid / pharmacology*

Substances

  • Cholagogues and Choleretics
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine