Eutherian Fetoembryonic Defense System (eu-FEDS) Hypothesis - Hypothesis

Hypothesis

The basic premise of the eu-FEDS hypothesis is that both soluble and cell surface associated glycoproteins, present in the reproductive system and expressed on gametes, suppress any potential immune responses, and inhibit rejection of the fetus. The eu-FEDS model further suggests that specific carbohydrate sequences (oligosaccharides) are covalently linked to these immunosuppressive glycoproteins and act as "functional groups" that suppress the immune response. The major uterine and fetal glycoproteins that are associated with the eu-FEDS model in the human include alpha-fetoprotein, CA125, and glycodelin-A (also known as placental protein 14 (PP14)).

Normally, a low level of these glycoproteins is detected in the maternal serum during the early stages of pregnancy. It appears that the effects of these eu-FEDS associated glycoproteins are manifested only during implantation and the very early development of the embryo. In humans, the expression of such glycoproteins greatly decreases toward the end of the first trimester. Therefore, more highly targeted mechanisms of immune suppression (such as the expression of the enzyme indoleamine dioxygenase (IDO)) are likely employed by the fetus during the subsequent stages of development. One potential reason for early inactivation of the system is that the immunosuppressive effect of these glycoproteins may be so complete that their continued leakage into the circulatory system could lead to a global suppression of the maternal immune response, compromising the mother's ability to carry the fetus to term.