Gili Paz, Shay Hantisteanu, Ofer Limonad, Rivka Frankel, Mordechai Hallak, Ofer Fainaru

Laboratory for Reproductive Immunology, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Faculty of Medicine, Technion – Israel Institute of Technology, Israel

Introduction: Immature myeloid cells (IMCs) differentiate in the steady state into mature granulocytes, macrophages and dendritic cells (DCs); nevertheless their population expands during malignant states. IMCs have been shown to function as immunosuppresors and promoters of angiogenesis. We have shown that IMCs display these functions in the developing placenta.  DCs are antigen-presenting cells that coordinate the immune response. They have also been shown to promote angiogenesis during implantation and early pregnancy. Our study seeks to determine whether alterations in myeloid cell populations affect placental development and to understand how aberrancies in their presence relate to pregnancy complications.

Materials and Methods: Placentas were harvested from timed pregnancies of C57Bl/6 mice. Placentas were immunostained and analyzed using flow cytometry. Kinetics of myeloid populations has been measured.

Results: The IMC population in the mouse placenta decreased throughout the latter part of pregnancy, (29±9.1%, 30±9.9%, 21±8.1% on days 12, 15, 18, respectively. n=63, P=0.004), conversely, the DC population in the mouse increased just before labor (0.87±0.3%, 0.7±0.3%, 1.81±1.3% on days 12, 15, 18, respectively n=63, P=0.001).

The population of neutrophils increased throughout pregnancy (28.3±7.9%, 17.5±9.3%, 30.4±2.3%, n=25, P=0.006. Whereas the populations of monocytes (21.5±5.3%, 16.7±3.7%, 10.6±3.4%, n=25, P=0.001) and macrophages (6.0±2.4%, 4.4±2.9%, 1.7±0.4%, n=25, P=0.035) decreased during pregnancy and just before labor, inducing sterile inflammation in the placenta.

Conclusions: In mice, our results indicate a reciprocal population shift between IMCs and DCs in the placenta during pregnancy. The possibility that the onset of labor and delivery is preceded by the maturation of IMCs into DCs and macrophages is intriguing. In addition to angiogenesis, these myeloid populations may have role in inducing inflammation in the placenta before labor and delivery.