Immature myeloid cells (IMCs) are bone marrow-derived cells that normally differentiate into granulocytes, macrophages, and dendritic cells (DCs) but expand in pathological conditions such as malignancy. We have previously shown that IMCs accumulate in the placenta, promote angiogenesis, peak in concentration during mid-pregnancy and their presence correlates with neonatal birthweight. We have recently demonstrated that progesterone (P) enhances the proliferation of bone marrow derived IMCs in vitro in a dose dependent manner. We thus speculated that P may play role in the maintenance of placental IMCs in vivo.
ICR pregnant mice (n=29) were pretreated with either vaginal P (1mg/day) or carrier (Replens) from day 13 to day 16 of gestation. Lipopolysaccharide (LPS) (500 μgr/kg) or vehicle was administered intrapertioneally at day 15 and at day 16. 4 hours after the last dose of LPS, mice were sacrificed and single cell suspensions derived from bone marrow and enzymatically digested placentas were immunostained and analyzed by flow cytometry. The CD45+CD11b+Gr1+ IMC and the CD45+CD11c+MHCII+ DC percentage out of total CD45+ hematopoietic cells in both bone marrow and placenta was calculated.
LPS treatment led to an increase in IMCs populating the bone marrow in both P pretreated (41.5±9.5 vs. 1.3±0.3 %, p=0.05) or vehicle pretreated mice (20.8±9.4 vs. 1.3±0.6 %, p=0.05). In the placenta, LPS led to a decline in IMCs only in mice that were not pretreated with P. Strikingly, P pretreatment led to complete abrogation of this effect and maintenance of an intact IMC population (control: 28.2±6.1; progesterone 29.6±4.7 ;LPS: 23.0±2.6; progesterone +LPS: 35.4±2.5 %; p=0.01). Interestingly, the population of DCs increased upon LPS treatment only in P non pretreated mice.
LPS treatment of pregnant mice induces premature labor by activating an inflammatory response. Here we show that LPS leads to a decrease in the placental proangiogenic IMC population and a corresponding increase in inflammatory DCs. This effect was completely abrogated in P pretreated mice. These results accord with our previous findings that P enhances the proliferation of bone marrow derived IMCs in vitro. We thus speculate that the protective effect of P in preventing preterm labor may be explained at least in part by this specific anti inflammatory effect.
© 2017 Published by Elsevier Inc.