1,721,069 research outputs found
Zika virus infection and pregnancy: what we do and do not know
Recent data strongly suggest an association between the current outbreak of ZIKA virus (ZIKV) in many countries of Central and South America and a sharp increase in the detection of microcephaly and fetal malformations. The link with brain defect, which has been detected mainly in some areas of Brazil, is supported by the following evidence: (1) ZIKV transmission from infected pregnant women to their fetuses; (2) the potential of ZIKV to determine a specific congenital fetal syndrome characterized by abnormalities involving primarily the developing brain and eye. In particular, the risk of transmission and congenital disease appears to be restricted to mother's infection during the first trimester of pregnancy. Among brain defects, microcephaly, brain calcifications, and ventriculomegaly are the most frequent abnormalities of the central nervous system detected so far. However, relevant information on effect of maternal infection with ZIKV on the fetus is still limited. In this review, we focus our attention on current knowledge about ZIKV infection in pregnancy, discussing relevant issues and open problems which merit further investigation
Clinical consequences of defective decidualization
Decidualization is characterized by a series of genetic, metabolic, morphological, biochemical, vascular and immune changes occurring in the endometrial stroma in response to the implanting embryo or even before conception and involves the stromal cells of the endometrium. It is a fundamental reproductive event occurring in mammalian species with hemochorial placentation. A growing body of experimental and clinical evidence strongly suggests that defective or disrupted decidualization contributes to the establishment of an inappropriate maternal-fetal interface. This has relevant clinical consequences, ranging from recurrent implantation failure and recurrent pregnancy loss in early pregnancy to several significant complications of advanced gestation. Moreover, recent evidence indicates that selected diseases of the endometrium, such as chronic endometritis and endometriosis, can have a detrimental impact on the decidualization response in the endometrium and may help explain some aspects of the reduced reproductive outcome associated with these conditions. Further research efforts are needed to fully understand the biomolecular mechanisms ans events underlying an abnormal decidualization response. This will permit the development of new diagnostic and therapeutic strategies aimed to improve the likelihood of achieveing a successful pregnancy
RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss
Unexplained recurrent pregnancy loss (uRPL) is associated with repeated embryo loss and endometrial repair with elevated endometrial expression of inflammatory cytokines, including IFN-γ. Notch signaling through its transcription factor recombination signal binding protein Jκ (RBPJ) regulates mechanisms including the immune response and repair after tissue injury. Initially, null mutation of RBPJ in the mouse uterus ( Pgrcre/+Rbpjf/f; Rbpj c-KO) results in subfertility, but we have found that these mice become infertile after pregnancy as a result of dysfunctional postpartum uterine repair, including delayed endometrial epithelial and myometrial regeneration. RNA sequencing of postpartum uterine repair sites revealed global up-regulation of inflammatory pathways, including IFN signaling. Consistent with elevated IFN-γ, macrophages were recruited and polarized toward an M1-cytotoxic phenotype, which is associated with preventing repair and promoting further tissue injury. Through embryo transfer experiments, we show that dysfunctional postpartum repair directly impairs future embryo implantation in Rbpj c-KO mice. Last, we clinically correlated our findings from the Rbpj c-KO mouse in women diagnosed with uRPL. Reduced RBPJ in women with uRPL was associated with increased levels of IFN-γ. The data, taken together, indicate that RBPJ regulates inflammation during endometrial repair, which is essential for future pregnancy potential, and its dysregulation may serve as an unidentified contributor to uRPL in women.-Strug, M. R., Su, R.-W., Kim, T. H., Mauriello, A., Ticconi, C., Lessey, B. A., Young, S. L., Lim, J. M., Jeong, J.-W., Fazleabas, A. T. RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss
What has to be pointed out in unexplained recurrent pregnancy loss research in the unsolved fields: Lessons from clinic. An Italian RPL Unit experience
Recurrent pregnancy loss (RPL) is a controversial field both in research and clinical approaches. Despite the most recent guidelines (ESHRE 2017), an agreement in diagnostic work-up to apply in these patients, as well as in management and treatment, has not been reached, especially in unexplained RPL (uRPL). This is due to the lack of a strong evidence-based level in this field, since the discrepancies among the different RPL research groups, in terms of definition, etiological factors and management cannot lead to organize all the results in systematic reviews. Therefore, common shared cornerstones are required to homogenize research parameters, since the right interplay between clinical management and experimental approaches could lead to contribute in the development of stronger evidences. In this review, we highlight what has to be pointed out in RPL debated subfields and how the experimental approach is necessary to overhaul discrepancies in clinical management. The experience of our RPL Unit has been reported to show how research experience could contribute in modifying the clinical approach
Oxytocin in human intrauterine tissues at parturition
The recent detection of oxytocin (OT) mRNA in human gestational tissues suggests that OT may be locally synthesized and released to act on the uterus as a local mediator in the mechanism of parturition. In order to investigate this possibility the OT immunoreactive (I.R.) content was examined directly in placental decidua and amniochorial membranes after term and preterm delivery and in their culture media at term gestation. I.R.OT concentrations were also measured in maternal, retroplacental and umbilical plasma as well as in amniotic fluid in the presence or the absence of labour. Low I.R.OT concentrations (below 15 fmol g-1 wet tissue) were found in both amniochorial membranes and placental decidua. Moreover, whereas in amniochorion they were higher (P < 0.05) after preterm than term spontaneous parturition, in decidua they were higher (P < 0.05) after term than preterm vaginal delivery. Detectable amounts (below 15 fmol g-1 wet tissue per h) of I.R.OT were also found in culture media from explants of the above tissues. Among all the examined maternal and fetal fluids a rise in I.R.OT content at parturition was detected only in the amniotic liquor (P < 0.05). These findings suggest that I.R.OT concentrations in intrauterine tissues are very low; however, considering that OT is the most potent endogenous uterotonic agent, OT as such concentrations might play a paracrine function in the biochemical events leading to human parturition. Therefore, a role for amniotic OT in parturition can not be excluded
Effect of oxytocin on nitric oxide production by human fetal membranes at term gestation
Estrogen replacement therapy and asthma
A growing body of clinical and experimental evidence indicates that female sex hormones, particularly estrogen, have significant effects on normal airway function as well as on respiratory disorders, such as asthma. These effects are very complex and are exerted at several levels, directly on airway reactivity or indirectly through regulation of the immune and inflammatory responses in the lung. They can have relevant clinical implications not only according to the phases of the reproductive life in women, but also in relation to the therapeutical administration of estrogen, as in the case of menopausal hormone therapy. Clinical evidence suggests that administration of estrogen to menopausal women is associated with increased rates of newly diagnosed asthma. Conversely, functional studies show that estrogen can improve objective indexes of respiratory functionality
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