Congenital cytomegalovirus infection in twin pregnancy

Cytomegalovirus (CMV) infection is one of the preeminent congenital viral infections, and despite its potential morbidity, uncertainty about its physiopathology, prevention and treatment remains until now. We report a case of a dichorionic and diamniotic twin pregnancy in which only one of the fetus had signs of being affected. The first twin had prenatal diagnosis of intrauterine growth restriction and hyperechogenic bowel, attributable to CMV infection, while there was no evidence of infection of the second one. Prenatal treatment was done with maternal administration of valacyclovir and postnatal treatment of the infected newborn with oral valganciclovir with normal neurodevelopment assessment at 12 months corrected age. In this case, maternal CMV infection was not equally transmitted to both fetuses, suggesting that there may be intrinsic fetal and placental factors influencing both transmission and the clinical features of the infection.

Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene

Fifty-five to two hundred CGG repeats (called a premutation, or PM) in the 5′-UTR of the FMR1 gene are generally unstable, often expanding to a full mutation (>200) in one generation through maternal inheritance, leading to fragile X syndrome, a condition associated with autism and other intellectual disabilities. To uncover the early mechanisms of pathogenesis, we performed metabolomics and proteomics on amniotic fluids from PM carriers, pregnant with male fetuses, who had undergone amniocentesis for fragile X prenatal diagnosis. The prenatal metabolic footprint identified mitochondrial deficits, which were further validated by using internal and external cohorts. Deficits in the anaplerosis of the Krebs cycle were noted at the level of serine biosynthesis, which was confirmed by rescuing the mitochondrial dysfunction in the carriers’ umbilical cord fibroblasts using alpha-ketoglutarate precursors. Maternal administration of serine and its precursors has the potential to decrease the risk of developing energy shortages associated with mitochondrial dysfunction and linked comorbidities.

Study on the effect of maternal administration of oxaliplatin on offspring testes using unbiased design-based stereology

Oxaliplatin (Ox) is widely used for the treatment of various tumors. Since Ox prevents DNA replication and transcription, it may affect organs with rapid cell divisions such as the testes. Although its use during pregnancy has been reported, no information regarding its effects on the testes of the offspring is not available yet. Thirty-two mice were randomly divided into four groups. The control group (1) was administered intraperitoneally 0.2 ml of saline three times a week for the 21 days of pre-pregnancy, pregnancy and lactation. Experimental groups 2, 3 and 4 received 3 mg/kg of oxaliplatin three times a week for 21 days during pre-pregnancy, pregnancy and lactation, respectively. The left testis was removed from male offspring 30 and 60 days after birth. The volume of the testes, seminiferous tubules and interstitial tissue, the surface area and height of the seminiferous epithelium, as well as the length and diameter of seminiferous tubules, were analyzed by means of stereology. Results showed a decrease in the evaluated parameters in experimental groups, in comparison with the control group. Due to the ameliorating effect of Ox on offspring testes, cautiousness is needed during maternal administration in order to preserve the fertility of male offspring.

β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

In animals and humans, offspring of allergic mothers have increased responsiveness to allergen and the allergen-specificity of the offspring can be different than that of the mother. In our preclinical models, the mother's allergic responses influence development of the fetus and offspring by elevating numbers of cells in dendritic cell subsets. A major question is the identity of maternal factors of allergic mothers that alter offspring development of responsiveness to allergen. Lipids are altered during allergic responses and lipids are transported to the fetus for growth and formation of fetal membranes. We hypothesized that pro-inflammatory lipids, that are elevated in allergic mothers, are transported to the fetus and regulate fetal immune development. We demonstrate in this report that there was a significant 2-fold increase in β-glucosylceramides (βGlcCer) in allergic mothers, the fetal liver and her offspring. The βGlcCer were transported from mother's plasma, across the placenta, to the fetus and in breastmilk to the offspring. Administration of βGlcCer to non-allergic mothers was sufficient for offspring responses to allergen. Importantly, maternal administration of a clinically relevant pharmacological inhibitor of βGlcCer synthase returned βGlcCer to normal levels in the allergic mothers and her offspring and blocked the offspring increase in dendritic cell subsets and offspring allergen responsiveness. In summary, allergic mothers had increased βGlcCer that was transported to offspring and mediated increases in offspring DCs and responsiveness to allergen. These data have a significant impact on our understanding of mechanisms for development of allergies in offspring of allergic mothers and have the potential to lead to novel interventions that significantly impact risk for allergic disease early in life.

Maternal exposure to polystyrene nanoplastics causes brain abnormalities in progeny

As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastics (PSNPs) on development of the central nervous system using cultured neural stem cells (NSCs) and mice exposed to PSNPs during developmental stages. Our study demonstrates that maternal administration of PSNPs during gestation and lactating periods altered the functioning of NSCs, neural cell compositions, and brain histology in progeny. Similarly, our in vitro study also shows PSNP-induced molecular and functional defects in NSCs. Finally, we show that the abnormal brain development caused by exposure to high concentrations of PSNPs results in neurophysiological and cognitive deficits in a gender-specific manner. Our data demonstrate the possibility that exposure to high amounts of PSNPs may increase the risk of neurodevelopmental defects.

Abstract P218: Tumor Necrosis Factor Alpha Improves Placental Perfusion And Attenuates Intrauterine Growth Restriction In A Rodent Model Of Preeclampsia

Preeclampsia ( PE ) is not only detrimental to the mother and her fetus during pregnancy, but it is also associated with increased cardiovascular ( CV ) risk in the mother and her intrauterine growth restricted ( IUGR ) offspring in later life. Currently there are no known treatment options for PE beyond early delivery. Thus, there is a critical need to identify therapeutic treatments for PE. The inflammatory cytokine TNF-α is increased in women with PE. In the clinically relevant Reduced Uterine Perfusion Pressure ( RUPP ) model of PE in the rat, TNF-α is also increased and importantly, etanercept abolishes maternal hypertension. Etanercept is a soluble receptor that binds TNF-alpha to inhibit the inflammatory response. Although not yet prescribed for PE, etanercept is non-contraindicated during pregnancy. Therefore, this study tested the hypothesis that maternal administration of etanercept will mitigate IUGR in the RUPP model of PE and that improvement in fetal growth occurs in association with improved uteroplacental perfusion, placental morphology, and placental nutrient transporter protein expression. Sham or RUPP was performed at gestational day 14 ( G14 ). Dams were administered vehicle or the TNF-α inhibitor (etanercept, 0.4 mg/kg, s.c.) at G18. At G20 uterine artery resistance index ( UARI ) was significantly increased in vehicle RUPP (0.69±0.02 mm/s) vs. vehicle Sham (0.60±0.02mm/s)( p <0.05), indicative of reduced uteroplacental perfusion, but UARI was no longer increased in treated RUPP (0.65±0.03 mm/s)( p <0.05). At G20, fetal weight was significantly reduced in vehicle RUPP (3.52g±0.10) vs. vehicle Sham (3.82 g±0.09)( p <0.05). Yet, fetal weight was significantly increased in treated RUPP (3.82g±0.12) vs. vehicle RUPP ( p <0.05). Fetal brain weight did not differ in Sham or RUPP, regardless of maternal treatment. However, fetal liver weight was significantly increased in treated RUPP (0.29g ±0.02) vs. vehicle RUPP (0.24g±0.01)( p <0.05) suggesting attenuation of asymmetric growth restriction. These findings indicate that maternal administration of a TNF-α inhibitor during PE improves fetal growth in association with improved uteroplacental blood flow. Future studies are warranted to investigate the long-term benefit in IUGR offspring.