Mifepristone (Ru486) antagonizes monocyte chemotactic protein-3 down-regulation at early mouse pregnancy revealing immunomodulatory events in Ru486 induced abortion.
OBJECTIVE
The survival of an embryo bearing the paternal antigens within the immunocompetent environment of the maternal uterus renders 'pregnancy' to be a state of immunological paradox. The ratio of Th1/Th2 responses is crucial for pregnancy maintenance. Monocyte Chemotactic Protein-3 (MCP3) is a pro-inflammatory, CC chemokine and a Th1 effector which is capable of eliciting significant anti-tumoral immune responses.


METHODS
MCP3 expression was investigated in the murine uterine tissue at different days of initial pregnancy and the effect of RU 486 in immature and delayed implantation model studied using Western blotting and Immunocytochemical techniques.


CONCLUSIONS
Our results show very high uterine MCP3 expression during pre-implantation followed by a significant MCP3 down-regulation at peri-implantation and low levels of MCP3 during post-implantation period. At the peri-implantation stage, embryos exhibited lowered MCP3 expression when compared with the pre-implantation stage. Ru486, a progesterone antagonist when given in a competitive mode with progesterone resulted in a massive surge in MCP3 expression in both immature mice and delayed implantation models. We hypothesize that it is imperative for MCP3 expression to be down-regulated for the success of pregnancy. The cross-talk between Ru486 and amplified MCP3 expression may be one of the mechanisms by way of which RU486 performs its abortificient and anti tumor role.
Nautiyal
Jaya
J
Embryo Implantation Group, Molecular Reproduction Unit, School of Life Sciences, Devi Ahilya Vishwavidyalaya, Vigyan Bhawan, Indore, Madhya Pradesh, India.
Kumar
Pradeep G
PG
Laloraya
Malini
M
D000028:Abortion, Induced; D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054410:Chemokine CCL7; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D010064:Embryo Implantation; D005260:Female; D006728:Hormones / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*; D023421:Models, Animal; D018945:Monocyte Chemoattractant Proteins / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology* / Q000502:physiology; D013997:Time Factors; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D006728:Hormones; D018945:Monocyte Chemoattractant Proteins; D015735:Mifepristone