Estrogen receptor 1 appears essential for fetal viability in a murine model of premature birth.

PROBLEM: Protective effects for adult neurological disorders have been attributed to sex hormones. Using a murine model of prematurity, we evaluated the role of estrogen signaling in the process of perinatal brain injury following exposure to intrauterine inflammation. METHOD OF STUDY: Intrauterine lipopolysaccharide (LPS) was used to invoke preterm labor and fetal neuroinflammation. Fetal brains were analyzed for changes in Esr1, Esr2 and Cyp19. Dams heterozygous for the Esr1 knockout allele were also given intrauterine LPS to compare delivery and offspring viability to wild type controls. RESULTS: The upregulation in inflammatory cytokines was accompanied by an increase in Esr1 and Esr2 transcripts, though protein levels declined. Cyp19 did not differ by mRNA or protein abundance. Offspring from Esr1 mutants were larger, had a longer gestation and significantly greater mortality. CONCLUSIONS: Estrogen signaling is altered in the fetal brains of preterm offspring exposed to neuroinflammatory injury. The reduction of Esr1 and Esr2 proteins with LPS suggests that these proteins are degraded. It is possible that transcriptional upregulation of Esr1 and Esr2 occurs to compensate for the loss of these proteins. Alternatively, the translation of Esr1 and Esr2 mRNAs may be disrupted with LPS while a feedback mechanism upregulates transcription. Intact Esr1 signaling is also associated with early preterm delivery following exposure to intrauterine LPS. A loss of one Esr1 allele delays this process, but appears to do so at the cost of fetal viability. These results suggest estrogen signaling plays opposing roles between maternal and fetal responses to preterm birth.

ZIKV can infect human term placentas in the absence of maternal factors.

Zika virus infection can result in devastating pregnancy outcomes when it crosses the placental barrier. For human pregnancies, the mechanisms of vertical transmission remain enigmatic. Utilizing a human placenta-cotyledon perfusion model, we examined Zika virus exposure in the absence of maternal factors. To distinguish responses related to viral infection vs. recognition, we evaluated cotyledons perfused with either active or inactivated Zika virus. Active Zika virus exposure resulted in infection, cell death and syncytium injury. Pathology corresponded with transcriptional changes related to inflammation and innate immunity. Inactive Zika virus exposure also led to syncytium injury and related changes in gene expression but not cell death. Our observations reveal pathologies and innate immune responses that are dependent on infection or virus placenta interactions independent of productive infection. Importantly, our findings indicate that Zika virus can infect and compromise placentas in the absence of maternal humoral factors that may be protective.

A Case Study of Puerperal Group A Streptococcal Infection Complicated by Toxic Shock Syndrome.

Puerperal infection with group A streptococcus (GAS), Streptococcus pyogenes , is associated significant morbidity and mortality. When associated with toxic shock syndrome (TSS), mortality rates rise to approximately 50%. We present the case of a 32-year-old Para 2 reporting severe left distal lower extremity pain, fevers, and chills at 1 week following an uncomplicated vaginal delivery. The patient's clinical status rapidly decompensated to septic shock requiring transfer to the intensive care unit. She underwent anterior and lateral compartment fasciotomy of the left lower extremity for concerns of possible necrotizing soft tissue infection. Final blood cultures confirmed GAS infection with unclear primary source, though endometritis was favored. She required additional orthopaedic procedures including an arthroscopy with washout for contralateral septic arthritis and myositis before her discharge on hospital day 19. She obtained a near-full recovery complicated by poor wound healing and permanent left foot drop. While GAS remains a rare puerperal event, obstetricians should recall there is a 20-fold increased incidence among postpartum women. Progression to TSS is associated with very poor prognosis and hysterectomy is often necessary. Favorable outcomes in GAS with or without TTS hinge on astute clinical suspicion, aggressive fluid resuscitation, early antibiotic therapy, and source control.

Perinatal Pyogenic Liver Abscess: A Rare Entity and First Reported Case of Klebsiella pneumoniae.

Introduction Pyogenic liver abscess (PLA) is a rare clinical entity, occurring in ∼2.3 per 100,000 patients. Perinatal PLA syndromes are exceedingly rare with just seven previously described cases in the literature and no prior Klebsiella-associated reports. Case A 29-year-old gravida 2 para 1 woman at 11 weeks gestation reporting fever, body aches, and headache. Search for an infectious source identified a 4-cm liver abscess. Percutaneous drainage confirmed Klebsiella pneumoniae infection. The patient was treated with antibiotics until imaging verified complete resolution of the abscess. Conclusion PLA is an uncommon etiology of sepsis in pregnancy. A thorough workup until a source was identified resulted in accurate diagnosis. This allowed for directed therapy and prompt recovery, undoubtedly contributing to favorable pregnancy outcomes in this first report of Klebsiella-associated perinatal PLA.

Evaluation of Sildenafil and Tadalafil for Reversing Constriction of Fetal Arteries in a Human Placenta Perfusion Model.

Fetal growth restriction resulting from reduced placental blood perfusion is a major cause of neonatal morbidity and mortality. Aside from intense surveillance and early delivery, there is no treatment for fetal growth restriction. A potential treatment associated with placental vasoconstriction is the class of PDE5 (phosphodiesterase type 5) inhibitors such as sildenafil, which is known to cross the placenta. In contrast, tadalafil, a more potent and selective PDE5 inhibitor has not been studied in pregnancy or experimental models of fetal growth restriction. Therefore, we compared the efficacy of these 2 PDE5 inhibitors for reversing vasoconstriction in an ex vivo human placental model and evaluating molecular and physiological responses. Sildenafil and tadalafil were infused into the intervillous space in a preconstricted human placental dual cotyledon, dual perfusion assay for the comparison of arteriole pressures and molecular indicators of drug inhibition. Results indicate a decrease arterial pressure with sildenafil citrate compared with controls, whereas tadalafil showed no difference. PDE5 and endothelial nitric oxide synthase activity were altered with sildenafil but not tadalafil. Sildenafil citrate improved preconstricted placental arterial perfusion in a human placental model, whereas tadalafil showed no response. It is possible that tadalafil did not cross the human placental barrier or was degraded by trophoblasts. This study supports human clinical trials exploring sildenafil as a potential treatment for improving fetal blood flow in fetal growth restriction associated with vasoconstriction.