BackgroundAlthough uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.Methodology/Principal FindingsUsing micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications.Conclusions/SignificanceThe molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

No abstract

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Objective To establish the long term effects of obstetric anal sphincter rupture.Design Prospective observational study.Setting University hospital in Sweden.Population Eighty-two women from a prospective study from 1990 to compare anorectal function after third degree tear. Methods Women completed a structured questionnaire, underwent a clinical examination and anorectal manometry, endoanal ultrasound (EAUSG) with perineal body measurement. Main outcome measures Symptoms of anal incontinence, sexual symptoms, anal manometry scores and evidence of sphincter damage on EAUSG. Results Five women had undergone secondary repair and three were lost to follow up. Fifty-one women (80%) completed the questionnaire. Twenty-six out of 46 (57%) of the original study group and 6/28 (20%) of the original controls were examined. Incontinence to flatus and liquid stool was more severe in the study group than in controls. Flatus incontinence was significantly more pronounced among women with subsequent vaginal deliveries. Mean maximal anal squeeze pressures were 69 mmHg in the partial rupture group and 42 mmHg in the complete rupture group (P ¼ 0.04). Study group women with signs of internal sphincter injury reported more pronounced faecal incontinence and had lower anal resting pressures (24 mmHg) than those with intact internal sphincters (40 mmHg) (P ¼ 0.01). Perineal body thickness of less than 10 mm was associated with incontinence for flatus and liquid stools, less lubrication during sex and lower anal squeeze pressures (58 mmHg vs 89 mmHg, P ¼ 0.04). Conclusions Subjective and objective anal function after anal sphincter injury deteriorates further over time and with subsequent vaginal deliveries. Thin perineal body and internal sphincter injury seem to be important for continence and anal pressure.

CD4+CD25high regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4+CD25− responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-α, and IFN-γ secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.