Trophoblast Major Histocompatibility Complex Class I Expression Is Associated with Immune-Mediated Rejection of Bovine Fetuses Produced by Cloning

Biol Reprod. 2016 Aug;95(2):39. doi: 10.1095/biolreprod.115.136523. Epub 2016 Jul 6.

Abstract

Trophoblast cells from bovine somatic cell nuclear transfer (SCNT) conceptuses express major histocompatibility complex class I (MHC-I) proteins early in gestation, and this may be one cause of the significant first-trimester embryonic mortality observed in these pregnancies. MHC-I homozygous-compatible (n = 9), homozygous-incompatible (n = 8), and heterozygous-incompatible (n = 5) SCNT pregnancies were established. The control group consisted of eight pregnancies produced by artificial insemination. Uterine and placental samples were collected on Day 35 ± 1 of pregnancy, and expression of MHC-I, leukocyte markers, and cytokines were examined by immunohistochemistry. Trophoblast cells from all SCNT pregnancies expressed MHC-I, while trophoblast cells from age-matched control pregnancies were negative for MHC-I expression. Expression of MHC-I antigens by trophoblast cells from SCNT pregnancies was associated with lymphocytic infiltration in the endometrium. Furthermore, MHC-I-incompatible conceptuses, particularly the heterozygous-incompatible ones, induced a more pronounced lymphocytic infiltration than MHC-I-compatible conceptuses. Cells expressing cluster of differentiation (CD) 3, gamma/deltaTCR, and MHC-II were increased in the endometrium of SCNT pregnancies compared to the control group. CD4(+) lymphocytes were increased in MHC-I-incompatible pregnancies compared to MHC-I-compatible and control pregnancies. CD8(+), FOXP3(+), and natural killer cells were increased in MHC-I heterozygous-incompatible SCNT pregnancies compared to homozygous SCNT and control pregnancies.

Keywords: cattle; immunohistochemistry; miscarriage; pregnancy; somatic cell nuclear transfer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • Cattle
  • Cloning, Organism*
  • Female
  • Fetus / immunology*
  • Histocompatibility Antigens Class I / metabolism*
  • Insemination, Artificial
  • Nuclear Transfer Techniques
  • Placenta / immunology
  • Placenta / metabolism*
  • Pregnancy
  • Trophoblasts / immunology
  • Trophoblasts / metabolism*
  • Uterus / immunology
  • Uterus / metabolism*

Substances

  • CD3 Complex
  • Histocompatibility Antigens Class I