Alterations in inflammatory, antiviral and regulatory cytokine responses in peripheral blood mononuclear cells from pregnant women with asthma

Background & objective: Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both the mother and the baby. Asthma exacerbations are caused most frequently by respiratory viruses. A balance between antiviral and inflammatory immune responses is critical during pregnancy; the balance may be altered by asthma and respiratory virus infection. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from (i) non-pregnant healthy controls, (ii) pregnant non-asthmatics, (iii) post-partum non-asthmatics, (iv) non-pregnant asthmatics (v) pregnant asthmatics, and (vi) post-partum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon (IFN)-, interleukin (IL)-10 and IL-17 protein were measured from culture supernatant. Neutrophil counts were obtained in samples from pregnant and post-partum women. Results: Following the phytohaemagglutinin stimulation of PBMCs, pregnant asthmatics had significantly higher IL-17 and significantly lower IFN- responses compared with healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in IFN- and IL-10 production from PBMC of pregnant asthmatics. The IL-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in IFN-, IL-10 and IL-17 were found to persist for at least 6 months post-partum. Conclusions: A reduction in antiviral and regulatory immunity with increased inflammation during pregnancy occurs in PBMC from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy

CD8 T cells and dendritic cells: key players in the attenuated maternal immune response to influenza infection

Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an immune response against invading pathogens. To achieve this, numerous changes must occur in the activity and function of maternal immune cells throughout the course of pregnancy. Respiratory viruses take advantage of these changes, altering the sensitive balance of maternal immunity, leaving the mother with increased susceptibility to viral infections and increased disease severity. Influenza virus is one of the most common respiratory virus infections during pregnancy, leading to an increased risk of ICU hospitalisations, pneumonia, acute respiratory distress syndrome and even death. Whilst much research has been performed to understand the changes that must take place in maternal immunity during pregnancy, considerable work is still needed to fully comprehend this tremendous feat. To date, few studies have focused on the alterations that occur in maternal immunity during respiratory virus infections. This review highlights the role of dendritic cells (DCs) and CD8 T cells during pregnancy, and the changes that occur in these antiviral cells following influenza virus infections

Facile Nucleophilic Addition to Salophen Coordinated to Nitridoosmium(VI)

STUDY QUESTION: What effect does multigenerational (F2) and transgenerational (F3) cigarette smoke exposure have on female fertility in mice? SUMMARY ANSWER: Cigarette smoking has a multigenerational effect on female fertility. WHAT IS KNOWN ALREADY: It has been well established that cigarette smoking decreases female fertility. Furthermore, a growing body of evidence suggests that smoking during pregnancy decreases the fertility of daughters and increases cancer and asthma incidence in grandchildren and great-grandchildren. STUDY DESIGN, SIZE, DURATION: Six-week-old C57BL/6 female mice were exposed nasally to cigarette smoke or room air (controls) for 5 weeks prior to being housed with males. Females continued to be exposed to smoke throughout pregnancy and lactation until pups were weaned. A subset of F1 female pups born to these smoke and non-smoke exposed females were bred to create the F2 grandmaternal exposed generation (multigenerational). Finally, a subset of F2 females were bred to create the F3 great-grandmaternal exposed generation (transgenerational). The reproductive health of F2 and F3 females was examined at 8 weeks and 9 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian and oocyte quality was examined in smoke exposed and control animals. A small-scale fertility trial was performed before ovarian changes were examined using ovarian histology and immunofluorescence and/ or immunoblotting analysis of markers of apoptosis (TUNEL) and proliferation (proliferating cell nuclear antigen (PCNA) and anti-Mullerian hormone (AMH)). Oocyte quality was examined using immunocytochemistry to analyze the metaphase II spindle and ploidy status. Parthenogenetic activation of oocytes was used to investigate meiosis II timing and preimplantation embryo development. Finally, diestrus hormone serum levels (FSH and LH) were quantified. MAIN RESULTS AND THE ROLE OF CHANCE: F2 smoke exposed females had no detectable change in ovarian follicle quality at 8 weeks, although by 9 months ovarian somatic cell proliferation was reduced (P = 0.0197) compared with non-smoke exposed control. Further investigation revealed changes between control and smoke exposed F2 oocyte quality, including altered meiosis II timing at 8 weeks (P = 0.0337) and decreased spindle pole to pole length at 9 months (P = 0.0109). However, no change in preimplantation embryo development was observed following parthenogenetic activation. The most noticeable effect of cigarette smoke exposure was related to the subfertility of F2 females; F2 smoke exposed females displayed significantly increased time to conception (P = 0.0042) and significantly increased lag time between pregnancies (P = 0.0274) compared with non-smoke exposed F2 females. Conversely, F3 smoke exposed females displayed negligible oocyte and follicle changes up to 9 months of age, and normal preimplantation embryo development. LARGE SCALE DATA: None LIMITATIONS, REASONS FOR CAUTION: This study focused solely on a mouse model of cigarette smoke exposure to simulate human exposure. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate that grandmaternal cigarette smoke exposure reduces female fertility in mice, highlighting the clinical need to promote cessation of cigarette smoking in pregnant women

Maternal smoke exposure impairs the long-term fertility of a female offspring in a murine model

The theory of fetal origins of adult disease was first proposed in 1989 and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. As mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood, however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility with maternal smoke exposed animals having smaller litters whilst taking longer to conceive. In conclusion our results demonstrate that in utero and lactational exposure to cigarette smoke can have long lasting effects on the fertility of the next generation of females

Investigating the Links between Lower Iron Status in Pregnancy and Respiratory Disease in Offspring Using Murine Models

Maternal iron deficiency occurs in 40–50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma. A low iron diet during pregnancy further increases these major disease features in offspring with experimental asthma. Importantly, a low iron diet increases neutrophilic inflammation, which is indicative of more severe disease, in asthma. Together, our data demonstrate that lower dietary iron and systemic deficiency during pregnancy can lead to physiological, immunological and anatomical changes in the lungs and airways of offspring that predispose to greater susceptibility to respiratory disease. These findings suggest that correcting iron deficiency in pregnancy using iron supplements may play an important role in preventing or reducing the severity of respiratory disease in offspring. They also highlight the utility of experimental models for understanding how iron status in pregnancy affects disease outcomes in offspring and provide a means for testing the efficacy of different iron supplements for preventing disease

TESS observations of cepheid stars: First light results

We present the first analysis of Cepheid stars observed by the TESS space mission in Sectors 1–5. Our sample consists of 25 pulsators: ten fundamental mode, three overtone and two double-mode classical Cepheids, plus three type II and seven anomalous Cepheids. The targets were chosen from fields with different stellar densities, both from the Galactic field and from the Magellanic System. Three targets have 2 minutes cadence light curves available by the TESS Science Processing Operations Center: for the rest, we prepared custom light curves from the full-frame images with our own differential photometric FITSH pipeline. Our main goal was to explore the potential and the limitations of TESS concerning the various subtypes of Cepheids. We detected many low-amplitude features: weak modulation, period jitter, and timing variations due to light-time effect. We also report signs of nonradial modes and the first discovery of such a mode in an anomalous Cepheid, the overtone star XZ Cet, which we then confirmed with ground-based multicolor photometric measurements. We prepared a custom photometric solution to minimize saturation effects in the bright fundamental-mode classical Cepheid, β Dor with the lightkurve software, and we revealed strong evidence of cycle-to-cycle variations in the star. In several cases, however, fluctuations in the pulsation could not be distinguished from instrumental effects, such as contamination from nearby sources, which also varies between sectors. Finally, we discuss how precise light-curve shapes will be crucial not only for classification purposes but also to determine physical properties of these stars. © 2021. The American Astronomical Society. All rights reserved