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Objective: 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. DCs are antigen-presenting cells that regulate the immune response. Both IMCs and DCs were shown to take part in angiogenesis; however, little is known of their function in the placenta. We sought to determine whether alterations in DC and IMC populations in the placenta precede the onset of delivery., Study Design: Experiments were performed on 6-8 week old C57Bl/6 female mice. Placentas from pregnant mice that were killed on designated days, immunostained using fluorescently labeled anti-CD11b, Gr-1, CD11c, major histocompatibility II (MHCII), and CD45, and analyzed by flow cytometry and immunofluorescent microscopy., Results: Throughout the latter part of pregnancy toward labor and delivery, the CD45(+)CD11b(+)Gr1(+)-IMC population decreased 29 ± 9.1% (day 12) and 30 ± 9.9% (day 15), vs 21 ± 8.1% (day18, n = 21, 15, and 27; P = .006 and P = .004, respectively), whereas the CD45(+)CD11c(+)MHCII(+)-DC population increased 0.87 ± 0.3% (day 12) and 0.70 ± 0.3% (day 15) vs 1.81 ± 1.3% (day 18, n = 21, 15, and 27, P = .002 and P = .001, respectively). Both myeloid cell populations were localized adjacent to CD31(+) endothelial cells in sites of placental angiogenesis., Conclusion: Labor and delivery are preceded by proangiogenic-myeloid cell alterations, reflected by a decrease in IMCs and an increase in DCs populating the mouse placenta. The intriguing possibility that delivery is preceded by the maturation of IMCs in part into DCs warrants further studies., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To determine whether CD11b(+)Gr1(+) immature myeloid cells (IMCs), initially identified to infiltrate tumors and support angiogenesis and recently identified also in mouse and human placentas, are similar in that they share common gene expression., Design: Animal experiment., Setting: Reproductive immunology laboratory., Animal(s): All 6- to 8-week-old C57Bl/6 female mice., Main Outcome Measure(s): We analyzed gene expression of IMCs isolated from placentas of pregnant mice (n = 3) and Lewis lung carcinoma tumors (n = 3), using flow cytometry. Expression patterns were compared to primary muscle cells (n = 4), using Affymetrix microarrays. Quantitative polymerase chain reaction (PCR) was used to validate microarray data. Similarity of gene expression was evaluated with the mass-distance algorithm., Result(s): The IMCs that infiltrate mouse placentas share ∼500 expressed genes with tumor IMCs (set a). This gene set is enriched with proangiogenic and inflammatory genes. Unique gene expression sets for tumor IMCs (set b) and placenta IMCs (set c) were also detected., Conclusion(s): The IMCs derived from placentas and tumors express common molecular signatures, suggesting similar origins and functions. This observation lends further support to the notion that the placenta uses a similar angiogenic machinery as tumors for survival and growth. Unique gene-sets, differentially expressed in tumor versus placenta-derived IMCs, may be required for specific IMC-hosting tissue interactions., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether proangiogenic immature myeloid cells are present in human placentas., Study Design: Biopsies were obtained from 61 placentas of term pregnancies. Percentage of CD45(+)CD33(+)LIN2(-)HLADR(-) immature myeloid cells of total CD45(+) hematopoietic cells was determined by flow cytometry. Location of immature myeloid cells in the placenta was identified using confocal microscopy. The proangiogenic potential of immature myeloid cells was analyzed by endothelial tube formation., Results: Immature myeloid cells comprise ∼25% of human placental CD45(+) hematopoietic cells and infiltrate placentas in proximity of blood vessels. The percentage of immature myeloid cells correlated positively with placental weight (r(2) = 0.108, P = .01) and birthweight (r(2) = 0.087, P = .02). Endothelial tube formation was increased in the presence of immature myeloid cells as compared with the presence of CD45(+)LIN2(+) control cells., Conclusion: Human placentas are populated by immature myeloid cells in the proximity of blood vessels. Consistent with their involvement in angiogenesis, immature myeloid cells accelerated endothelial tube formation. The presence of immature myeloid cells in pathologic pregnancies warrants further studies., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: We sought to determine whether CD11b(+)Gr1(+) immature myeloid cells (IMCs), which have been shown to promote tumor angiogenesis, accumulate in the placenta and similarly contribute to blood vessel formation., Study Design: Experiments were performed on 6- to 8-week-old C57Bl/6J female mice. Placentas from pregnant mice or B16F10 tumors that were subcutaneously implanted were analyzed by flow cytometry and confocal microscopy. To determine the proangiogenic potential of IMCs, Matrigel plug assays were performed., Results: IMCs infiltrate the placenta in the proximity of blood vessels, reaching peak concentration at midpregnancy. When isolated from either placentas or B16F10 melanoma tumors, IMCs actively promoted endothelial cell migration into Matrigel plugs in vivo. Furthermore, placental IMCs, similar to tumor-derived IMCs, expressed matrix metalloproteinase-9 and Bv8, 2 pivotal proangiogenic proteins., Conclusion: IMCs that express matrix metalloproteinase-9 and Bv8 infiltrate placentas of pregnant mice and actively promote angiogenesis. These cells show striking similarity to IMCs that populate malignant tumors., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To investigate placental apoptosis in discordant dichorial twins., Methods: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome., Results: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the latter (P< 0.02 Wilcoxon rank test)., Conclusions: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted., (Copyright 2002 Elsevier Science Ltd.)