Altered crosstalk of estradiol and progesterone with Myeloid-derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal-fetal tolerance

Problem Decline in myeloid-derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation. Method of study Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G-MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor -alpha (ER-alpha), STAT-3/pSTAT-3, and caspase-3, respectively. Results Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G-MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER- alpha and increased caspase-3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT-3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT-3 indicates that these processes pertaining to MDSCs are compromised. Conclusion Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal-fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy.