Activation of latent transforming growth factor (TGF)-β in seminal plasma has been suggested by Robertson et al. to promote maternal tolerance to paternal antigens. A possible consequence reported by Tremellen et al. is increased pregnancy rates in women undergoing IVF. A decreased spontaneous abortion rate has also been postulated. Seminal plasma contains many factors besides TGF-β, and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF-β.
Method of study
Pharmaceutical grade bioactive TGF-β3 with a bovine serum albumin (BSA) carrier 0.1–1% in phosphate-buffered saline (PBS) was given into the vaginal tract of CBA/J female mice at the time of mating with DBA/2 males. One microgram Salmonella enteritidis lipopolysaccharide was given intraperitoneally to augment occult losses and spontaneous resorptions assessed on day 13.5 of pregnancy. The effect of TGF-β3 on recruitment of lymphomyeloid cells to the vaginal wall and vaginal lumen of unmated mice in estrus was assessed using immunohistochemistry and flow cytometry.
Two nanogram of intravaginal TGF-β3 in 0.1% BSA–PBS or 20 ng in 1% BSA–PBS reduced abortion rates. Protection was comparable to that achieved by immunization with BALB/c spleen cells. Fraction V BSA, a binder of TGF-βs, had some activity, and could reduce availability of added TGF-β3. CD11c dendritic cells, CD3+ T cells, and CD25+ cells were recruited to the vaginal wall by 48 hr after TGF-β3 treatment, and cellularity of vaginal exudates increased. Foxp3+ cells were present in increased numbers, and appeared to be CD8+ and CD4+ 8+. Semen, but not TGF-β3, stimulated a physiological polymorphonuclear leukocyte exudate.
Intravaginal bioactive TGF-β3 can enhance success of pregnancy in vivo in an established model of abortion. The result could be explained by the independent ability of TGF-β to promote a regulatory T-cell response.