title: Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4.
abstract: Immune regulation during pregnancy is complex, and thus an optimal therapy for pregnancy complications is always a big challenge to reproductive medicine. Cyclosporin A (CsA), a potent immunosuppressant, prevents rejection of allografts by hosts, but little is known about the modulating effect of CsA on the materno-fetal relationship. Here, pregnant CBA/J females mated with DBA/2 males as an abortion-prone model were administered with CsA on day 4.5 of gestation, and the pregnant CBA/J females mated with BALB/c males were established as successful pregnancy control. It was demonstrated that administration of CsA at the window of implantation significantly up-regulated the expression of CTLA-4, while down-regulating the levels of CD80, CD86, and CD28 at the materno-fetal interface in the CBA/J x DBA/2 abortion-prone matings, and the embryo resorption rate of the abortion-prone matings reduced significantly after CsA treatment, implying that modulation of costimulatory molecule expression by CsA might contribute to preventing the fetus from maternal immune attack. In addition, treatment with CsA induced enhanced growth and reduced cell apoptosis of the murine trophoblast cells. Together, these findings indicate that CsA has a beneficial effect on the materno-fetal interface in abortion-prone matings, leading to a pregnancy outcome improvement, which might provide new therapeutics for spontaneous pregnancy wastage.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Du
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhu
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001947:Breeding; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D016572:Cyclosporine / Q000627:therapeutic use*; D015536:Down-Regulation; D010064:Embryo Implantation / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D023421:Models, Animal; D011247:Pregnancy; D011256:Pregnancy Outcome; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007166:Immunosuppressive Agents; D016572:Cyclosporine