CD40 ligand and CD40: expression, regulation and function at the maternal-conceptus interface in pigs

Area of Science:

• Reproductive immunology
• Cellular and molecular biology

Background:

• Pregnancy establishment in pigs requires a balanced maternal-conceptus immune environment.
• Cluster of differentiation ligand 40 (CD40L) and its receptor CD40 are expressed in the pig endometrium during early pregnancy.
• The specific roles of CD40L-CD40 signaling in porcine pregnancy are not fully understood.

Purpose of the Study:

• To investigate the expression, regulation, and function of the CD40L-CD40 system at the maternal-conceptus interface in pigs.
• To determine the impact of CD40L-CD40 signaling on endometrial endothelial cells during early pregnancy.

Main Methods:

• Transcriptomics analysis to identify CD40L and CD40 expression.
• Immunohistochemistry to localize CD40L and CD40 proteins in endometrial tissues.
• In vitro studies using cultured porcine uterine endothelial (pENDO) cells to assess CD40L function.
• Interferon-gamma treatment of endometrial explants to study regulatory effects.

Main Results:

• CD40L and CD40 mRNA levels peaked in the endometrium on day 15 of pregnancy.
• CD40L protein localized to luminal epithelial cells, while CD40 was found in epithelial, stromal, and endothelial cells.
• Conceptus expressed CD40 early in pregnancy, with both CD40L and CD40 present later.
• Interferon-gamma upregulated CD40L and CD40 expression in endometrial explants.
• CD40L promoted pENDO cell migration and altered expression of genes involved in angiogenesis, adhesion, chemokines, and immunity.

Conclusions:

• The CD40L-CD40 system is expressed and functional at the maternal-conceptus interface in pigs.
• This signaling pathway likely plays a significant role in regulating endometrial endothelial cell function.
• CD40L-CD40 signaling contributes to the establishment of pregnancy by modulating the uterine immune environment and endothelial cell behavior.