Immunoneutralization of endometrial monoclonal nonspecific suppressor factor beta (MNSFbeta) inhibits mouse embryo implantation in vivo.
Successful embryo implantation and pregnancy in mammals depends on the establishment of immune tolerance between the maternal immune system and fetal cells. Monoclonal nonspecific suppressor factor beta (MNSFbeta), a cytokine produced by suppressor T cells in various tissues, possesses an antigen-nonspecific immune-suppressive function, and may be involved in the regulation of the uterine immune response during embryo implantation. In this study, anti-MNSFbeta IgG administered directly into the uterine lumen, significantly inhibited mouse embryo implantation in a dose-dependent manner in vivo, and this effect was reversed by co-administration of recombinant MNSFbeta. The effects of anti-MNSFbeta IgG on the gene pattern profiles in mouse uterine tissues were examined by cDNA microarray and several changes were confirmed by real-time PCR. Anti-MNSFbeta IgG caused up-regulation (> or = 2-fold) of 71 known genes and 17 unknown genes, and decreased expression (> or = 2-fold) of 74 known genes and 43 unknown genes, including several genes previously associated with embryo implantation or fetal development. Most of the known genes are involved in immune regulation, cell cycle/proliferation, cell differentiation/apoptosis, and lipid/glucose metabolism. These results demonstrate that MNSFbeta plays critical roles during the early pregnancy via multiple pathways.
Wang
Jian
J
Key Laboratory of Contraceptives and Devices of National Population and Family Planning Committee, Shanghai Institute of Planned Parenthood Research, Shanghai, China.
Huang
Zhe Ping
ZP
Nie
Gui Ying
GY
Salamonsen
Lois A
LA
Shen
Qing Xiang
QX
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects* / Q000235:genetics; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D007313:Insecta / Q000166:cytology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013491:Suppressor Factors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology
D000906:Antibodies; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; C072169:monoclonal nonspecific suppressor factor