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PROBLEM: Nitric oxide (NO), an important mediator of the inflammatory response, is involved in several reproductive processes including pregnancy and labor. Uterus, placenta and fetal membranes are significant sources of NO. Presently, there is no information on factors regulating NO production by fetal membranes. METHOD OF STUDY: Human fetal membranes at term gestation were cultured for 24 hr in the presence of oxytocin. The concentrations of NO metabolites nitrites in culture medium were determined by the Griess reaction. The presence of inducible nitric oxide synthase (iNOS) was determined by reverse transcriptase-polymerase chain reaction and Western blot. RESULTS: Oxytocin increased nitrite release by fetal membranes. Messenger ribonucleic acid iNOS expression was also enhanced by oxytocin. These effects were more marked in tissues obtained after labor than before labor. CONCLUSIONS: Oxytocin exerts an overall stimulatory effect on NO release by fetal membranes. This action might be of relevance in the biomolecular processes leading to parturition. [ABSTRACT FROM AUTHOR]

Presents a study that determined the migration inhibitory factor (MIF) concentration profiles in peripheral venous blood and amniotic fluid at midtrimester and at term in uncomplicated pregnancies. Description and function of MIF; Reproductive events in which MIF participates; Effect of the type of delivery on MIF concentrations; Discussion on term extraembryonic membranes as potential sources of MIF.

Problem: While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy., Method of Study: Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4 + T cells into immune regulatory phenotypes, as detected by flow cytometry., Results: Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls., Conclusion: Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the present manuscript, we review the recent research investigating the pathogenic association between most studied autoantibodies and recurrent pregnancy loss. Pregnancy loss represents a common obstetric complication occurring in about 15%-25% of all clinically recognized pregnancies. The recurrence of pregnancy loss identifies a distinct clinical entity, that is recurrent pregnancy loss (RPL), affecting about 2%-4% of couples. Several factors, including age, chromosomal abnormalities, uterine anomalies, thrombophilic disorders, endocrinopathies, hormonal and metabolic disorders, infections, sperm quality, and lifestyle issues, are involved in RPL. The role of autoantibodies in RPL is only partially determined. In some cases (antiphospholipid antibodies [aPL]), their involvement is well established. In other cases (anti-thyroid autoantibodies, antinuclear, anti-transglutaminase, and anti-endomysial antibodies), it is still debated, despite multiple, although not fully conclusive, evidences strongly suggest a possible involvement in RPL. Further extensive research is needed to definitively confirm or exclude their actual role., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: To investigate whether antinuclear autoantibodies (ANA) could be related to the outcome of the successive pregnancy in women with unexplained recurrent miscarriage (uRM)., Methods: Circulating ANA were measured by indirect immunofluorescence in 86 women with uRM before pregnancy, repeated in the first trimester of the successive gestation and correlated with pregnancy outcome., Results: Forty-one women were ANA- and 45 were ANA+ before pregnancy. No relation was found between pre-pregnancy ANA status and the outcome of the successive pregnancy. However, when these women were monitored at 7th week during their pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages (31.8%) were observed, whereas all of the 23 ANA+ women who became ANA- had pregnancies ongoing beyond the 20th week without miscarriage., Conclusions: ANA status could have a role in uRM. Disappearance of ANA in early pregnancy could have a favorable prognostic value in the successive pregnancy., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: To investigate the possible relationship between human papillomavirus (HPV) infection and recurrent miscarriage (RM)., Methods: In this retrospective case-control study, 49 women with unexplained RM (Group 1 - cases) and 475 women without any miscarriage and with at least one pregnancy at term (Group 2 - controls) were checked for cervical HPV infection through Hybrid Capture(®) II (HC 2) or polymerase chain reaction (PCR)., Results: HPV+ DNA tests were detected in 13 (26.53%) RM women and in 294 (61.89%) control women (P < 0.001). The prevalence rate in HPV+DNA tests was significantly different in the 30-39 years age range. No differences between groups were detected in HPV types, nor in the cytological and histological findings., Conclusion: Women with RM have a lower prevalence of HPV+DNA tests than controls. This suggests that immune reactivity potentially leading to RM could be in some way protective against genital HPV infection., (© 2013 John Wiley & Sons Ltd.)

Problem: To investigate the role of antithyroid autoantibodies (ATA) in recurrent miscarriage (RM)., Methods: In this case-control study, a total of 160 women with RM and 100 healthy women were investigated for the presence of serum ATA directed against thyreoglobulin (TG-Ab), thyroid peroxidase (TPO-Ab) and TSH receptor (TSHr-Ab), which were determined by either chemiluminescence or radioimmunoassay., Results: Antithyroid autoantibodies were detected in 46 (28.75%) women with RM and in 13 (13%) women of the control group (P < 0.05). The frequencies for TG-Ab and TPO-Ab were higher in RM than in control women. Among the women of RM group, 91.3% of ATA+ women were positive also for other autoantibodies. The majority of study women were euthyroid., Conclusions: Antithyroid autoantibodies, particularly TG-Ab, are associated with RM and could be an expression of a more general maternal immune system abnormality leading to RM. ATA could have a role in RM irrespective of thyroid hormone status., (© 2011 John Wiley & Sons A/S.)

Problem: To investigate the possibility that antinuclear antibodies (ANA) are involved in recurrent pregnancy loss (RPL)., Methods: Case-control study carried out on 294 women (194 cases and 100 controls) in two University hospitals. The presence, the serum titers and the indirect immunofluorescence (IIF) patterns of ANA were determined in women with RPL and in control women., Results: Antinuclear antibodies at titers ≥ 1:80 were detected in 97 (50%) women with RPL and in 16 (16%) control women. Elevated ANA titers (≥1:180) were detected only in RPL women, whereas all control women had ANA titers no greater than 1:80. No differences could be detected in the IIF patterns between RPL and control women. No differences in ANA positivity could be detected according to the type (primary or secondary) or number (>2 versus ≥3) of losses., Conclusions: ANA could be of some value in identifying women with RPL with potential, although still not fully defined, immune abnormalities., (© 2010 John Wiley & Sons A/S.)