Maternal or fetal origin of rhesus monkey (<i>Macaca mulatta</i>) amniotic fluid leukocytes can be identified by polymerase chain reaction using the zinc finger Y gene

American Journal of Obstetrics and Gynecology

et al. 2017

100

101

Background Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intra-amniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils. Objectives To investigate the origin of amniotic fluid neutrophils from women with intra-amniotic infection and/or inflammation, and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta. Study Design Amniotic fluid was collected from 15 women with suspected intra-amniotic infection and/or inflammation (positive microbiological cultures and/or interleukin (IL)-6 concentrations≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization (FISH) was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted. Results 1) DNA fingerprinting revealed that 43% (6/14) of the women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid; 2) DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid; 3) DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid; 4) DNA fingerprinting revealed that a woman who underwent two amniocenteses (patient #15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity ; 5) FISH confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils are present in the amniotic fluid; 6) Most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates [71% (5/7)]; 7) All of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates [100% (6/6)]; 8) Two of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates [67% (2/3)], and the third woman delivered a term neonate [33% (1/3)]; and 9) Most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta [87 % (13/15)]. Conclusion Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intra-amniotic inf...

Section: Strengths and Limitationssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Are amniotic fluid neutrophils in women with intraamniotic infection and/or inflammation of fetal or maternal origin?

American Journal of Obstetrics and Gynecology

et al. 2017

100

101

“…A central question that requires further investigation is whether amniotic fluid neutrophils in cases with intra‐amniotic infection and/or inflammation are of maternal and/or fetal origin. These innate immune cells are thought to be predominantly of fetal origin and invade the amniotic cavity by migrating from the fetal vessels of the chorionic plate . However, abundant neutrophils have also been observed in the amniotic fluid of patients with a severe maternal inflammatory response but without a fetal inflammatory response, indicating that there is a possibility that these innate immune cells are of maternal origin or a mixture of both fetal and maternal neutrophils .…”

Section: Discussionmentioning

confidence: 99%

Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity

Garcia‐Flores

et al. 2017

American J Rep Immunol

Problem Neutrophils are capable of performing phagocytosis, a primary mechanism for microbial killing. Intra-amniotic infection is characterized by an influx of neutrophils into the amniotic cavity. Herein, we investigated whether amniotic fluid neutrophils could phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection. Methods Amniotic fluid neutrophils from women with intra-amniotic infection were visualized by transmission electron microscopy (n=6). The phagocytic activity of amniotic fluid neutrophils from women with intra-amniotic infection and/or inflammation (n=10) or peripheral neutrophils from healthy individuals (controls, n=3) was tested using ex vivo phagocytosis assays coupled with live imaging. Phagocytosis by amniotic fluid neutrophils was also visualized by confocal microscopy (n=10) as well as scanning and transmission electron microscopy (n=5). Results 1) Intra-amniotic infection-related bacteria including cocci (e.g. Streptococcus agalactiae), bacilli (e.g. Bacteriodes fragilis and Prevotella spp.), and small bacteria without a cell wall (e.g. Ureaplasma urealyticum) were found inside of amniotic fluid neutrophils; 2) peripheral neutrophils (controls) rapidly phagocytized Streptococcus agalactiae, Ureaplasma urealyticum, Gardnerella vaginalis, and Escherichia coli; 3) amniotic fluid neutrophils can rapidly phagocytize Streptococcus agalactiae and Gardnerella vaginalis; and 4) amniotic fluid neutrophils can slowly phagocytize Ureaplasma urealyticum and Escherichia coli; yet, the process of phagocytosis of the genital mycoplasma was lengthier. Conclusions Amniotic fluid neutrophils can phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection, namely Streptococcus agalactiae, Ureaplasma urealyticum, Gardnerella vaginalis, and Escherichia coli. Yet, differences in the rapidity of phagocytosis were observed among the studied microorganisms. These findings provide a host defense mechanism whereby amniotic fluid neutrophils can kill microbes invading the amniotic cavity.

“…Given that fetal immune cells can be detected in the amniotic cavity even in the absence of inflammation (51,(81)(82)(83)(84), we proposed the study of amniotic fluid immune cells as a window into the fetal immune system in utero. Using clinical and immunological tools, we aimed to investigate whether fetal T cells are implicated in the pathophysiology of idiopathic preterm labor, which occurs in the absence of intra-amniotic inflammation.…”

mentioning

confidence: 99%

Fetal T Cell Activation in the Amniotic Cavity during Preterm Labor: A Potential Mechanism for a Subset of Idiopathic Preterm Birth

The Journal of Immunology

et al. 2019

Prematurity is the leading cause of perinatal morbidity and mortality worldwide. In most cases, preterm birth is preceded by spontaneous preterm labor, a syndrome that is associated with intra-amniotic inflammation, the most studied etiology. However, the remaining etiologies of preterm labor are poorly understood; therefore, most preterm births are categorized as idiopathic. In this study, we provide evidence showing that the fetal immune system undergoes premature activation in women with preterm labor without intra-amniotic inflammation, providing a potential new mechanism of disease for some cases of idiopathic preterm birth. First, we showed that fetal T cells are a predominant leukocyte population in amniotic fluid during preterm gestations. Interestingly, only fetal CD4 + T cells were increased in amniotic fluid of women who underwent idiopathic preterm labor and birth. This increase in fetal CD4 + T cells was accompanied by elevated amniotic fluid concentrations of T cell cytokines such as IL-2, IL-4, and IL-13, which are produced by these cells upon in vitro stimulation, but was not associated with the prototypical cytokine profile observed in women with intra-amniotic inflammation. Also, we found that cord blood T cells, mainly CD4 + T cells, obtained from women with idiopathic preterm labor and birth displayed enhanced ex vivo activation, which is similar to that observed in women with intra-amniotic inflammation. Finally, we showed that the intra-amniotic administration of activated neonatal CD4 + T cells induces preterm birth in mice. Collectively, these findings provide evidence suggesting that fetal T cell activation is implicated in the pathogenesis of idiopathic preterm labor and birth.