Trefoil factor family peptides in the human foetus and at birth

Trefoil factors (TFF1-3) are cysteine-rich peptides secreted by mucosal surfaces. Changing levels of expression are reflected in serum concentrations. Serum levels of TFF2 and TFF3 are highly elevated during pregnancy. Here, we explore a possible foetal origin of these increased levels.

We examined the expression of trefoil peptides in foetal tissues, placentas and foetal membranes from midterm abortions by immunohistochemistry. Employing in-house ELISAs, serum concentrations of TFF1-3 were measured in 92 paired samples of cord and maternal blood prior to delivery. Size exclusion chromatography was used to investigate the molecular forms of TFF1-3.

Immunohistochemistry showed all trefoil peptides to be present during foetal life, but compared to adults with a more widespread expression of TFF2 and TFF3 in the stomach and Brunner's glands. No trefoil peptides were seen in placentas or foetal membranes. Median serum concentrations of TFF1 in cord blood were comparable to those observed in the (mother) [0·42 (0·37) nM, P = 0·25], whereas TFF2 and TFF3 showed lower values than in the mother [0·11 (0·69), and 1·2 (6·7) nM, respectively, P < 0·0001 for both peptides]. Size exclusion chromatography showed comparable patterns in mothers and newborns.

All three trefoil peptides are expressed in foetal tissues but not in placenta or foetal membranes. Cord blood contains high levels of all three peptides, although for TFF2 and TFF3 at considerably lower levels than observed in the mother. Thus, the elevated serum levels of TFF2 and TFF3 in the pregnant women were most likely not of foetal origin.