Fibrinogen in equine pregnancy as a mediator of cell adhesion, an epigenetic and functional investigation.

The research looks at fibrinogen in horse embryos and its role in cell adhesion during the early stages of pregnancy. It also explores the possibility that fibrinogen expression is regulated by DNA methylation in fetal tissue.

Key Findings

• The research found that equine embryos produce and secrete fibrinogen during the preimplantation stage. In most cases, fibrinogen synthesis is primarily an activity of the liver, so its production by the embryos is notable.
• On the 21st day of pregnancy, it was noticed that the transcript abundance of five integrin subunits (ITGA5, ITGB1, ITGAV, ITGB1) were significantly higher than on day 16. This suggests that there is increased cell adhesion activity during this period. The outcome of an in vitro cell adhesion assay supports the hypothesis that fibrinogen from the conceptus (embryo) facilitates cell adhesion.
• Fibrinogen transcripts were found in the bilaminar trophoblast and allantochorion, suggesting that fibrinogen expression continues even past the fixation period. This suggests that fibrinogen might have multiple roles beyond just cell adhesion, including trapping growth factors and triggering signal cascades.
• The paper then compares the role of fibrinogen in pregnancy to its role in cancer; fibrinogen expression in tumors, particularly breast carcinoma, plays a role in the metastasis of circulating tumors.

DNA Methylation and Fibrinogen Expression

• The study also explores the DNA methylation of the fibrinogen locus in the conceptus, comparing it to the liver and endometrium. It was found that the endometrium had significantly high DNA methylation across the full gene cluster compared to both the liver and conceptus.
• However, the DNA methylation of the regulatory regions did not vary between the liver and conceptus and were significantly lower than in the endometrium. This suggests that DNA methylation could be controlling the expression of fibrinogen in the conceptus.

Conclusions

• The research supports the hypothesis that fibrinogen from horse embryos mediates cell adhesion during pregnancy and its expression maybe regulated by DNA methylation in the fetal tissue.
• This study brings to light new understanding on the role of fibrinogen during pregnancy and could have profound implications for both reproductive and cancer biology research.