TGF-beta1 Secretion in Response to Trophoblast Antigen and Progesterone in Women with Unexplained Recurrent Spontaneous Abortion

Choi, B C; Hill, Joseph A

Abstract

Cross reacting properties of Th1-type and Th2-type cytokines have been proposed to play a role in both murine and human early pregnancy with Th2-type cytokines associated successful pregnancy and Th1-type cytokines with pregnancy loss. TGF-beta1 is an important immunoregulatory molecule which can either promote or inhibit Th1-type immunity depending on the susceptibility of T-cells to produce IL-2. The purpose of this study was to determine the ability of peripheral blood mononuclear cells[PBMCs] from women with and without unexplained recurrent abortion[URA] to secrete TGF-beta1 following exposure to trophoblast and to determine whether progesterone at levels attained at the maternal-fetal interface[10-5M], affected TGF-beta1 secretion in these cultures. PBMCs were isolated from 30 nonpregnant women with URA and from 10 non pregnant fertile controls. Following 4 days of culture [1x106 cells/mL] with and without trophoblast extract[30 microgram/mL] and with and without progesterone[10-5M]. TGF-beta1 was measured by ELISA. Women with URA[median 4, range 2-12] had significantly lower levels of TGF-beta1 in unstimulated culture supernatants compared to fertile controls [0.87+/- 0.08 ng/mL vs. 1.47+/-0.22 ng/mL; p<0.05]. TGF-beta1 levels were not affected by trophoblast or progesterone in women with URA[0.97+/-0.11 ng/mL vs. 0.95+/-0.09 ng/mL, respectively]. Incontrast, TGF-beta1 levels were significantly decreased in trophoblast stimulated compared to unstimuated PBMC cultures from fertile controls [0.92+/-0.21 ng/mL vs. 1.47+/-0.22 ng/mL; p<0.05]. TGF-beta1 secretion in fertile women in response to trophoblast was attenuated by progesterone[0.92+/-0.21ng/mL vs. 1.09+/-0.20ng/mL, relatively]. These data indicate that there are significant differences in TGF-beta1 regulation in reponse to trophoblast and progesterone between women with URA and women with normal reproductive histories.