J. Dev. Biol., Volume 11, Issue 4 (December 2023) – 4 articles

This review focuses on SARS-CoV-2 infection in placental and fetal tissues. Viremia is rare in infected pregnant women, and the virus is seldom amplified from placental tissues. Definite and probable placental infection requires the demonstration of viral RNA or proteins using in situ hybridization (ISH) and immunohistochemistry (IHC). Small subsets (1.0–7.9%, median 2.8%) of placentas of SARS-CoV-2-positive women showed definite infection accompanied by a characteristic histopathology named SARS-CoV-2 placentitis (SP). The conventionally accepted histopathological criteria for SP include the triad of intervillositis, perivillous fibrin deposition, and trophoblast necrosis. SP was shown to be independent of the clinical severity of the infection, but associated with stillbirth in cases where destructive lesions affecting more than 75% of the placental tissue resulted in placental insufficiency and severe fetal hypoxic–ischemic injury. An association between maternal thrombophilia and SP was shown in a subset of cases, suggesting a synergy of the infection and deficient coagulation cascade as one of the mechanisms of the pathologic accumulation of fibrin in affected placentas. The virus was amplified from fetal tissues in approximately 40% of SP cases, but definite fetal involvement demonstrated using ISH or IHC is exceptionally rare. The placental pathology in SARS-CoV-2-positive women also includes chronic lesions associated with placental malperfusion in the absence of definite or probable placental infection. The direct viral causation of the vascular malperfusion of the placenta in COVID-19 is debatable, and common predispositions (hypertension, diabetes, and obesity) may play a role. Full article

The presence of farnesylated proteins at the inner nuclear membrane (INM), such as the Lamins or Kugelkern in Drosophila, leads to specific changes in the nuclear morphology and accelerated ageing on the organismal level reminiscent of the Hutchinson–Gilford progeria syndrome (HGPS). Farnesyl transferase inhibitors (FTIs) can suppress the phenotypes of the nuclear morphology in cultured fibroblasts from HGPS patients and cultured cells overexpressing farnesylated INM proteins. Similarly, FTIs have been reported to suppress the shortened lifespan in model organisms. Here, we report an experimental system combining cell culture and Drosophila flies for testing the activity of substances on the HGPS-like nuclear morphology and lifespan, with FTIs as an experimental example. Consistent with previous reports, we show that FTIs were able to ameliorate the nuclear phenotypes induced by the farnesylated nuclear proteins Progerin, Kugelkern, or truncated Lamin B in cultured cells. The subsequent validation in Drosophila lifespan assays demonstrated the applicability of the experimental system: treating adult Drosophila with the FTI ABT-100 reversed the nuclear phenotypes and extended the lifespan of experimentally induced short-lived flies. Since kugelkern-expressing flies have a significantly shorter average lifespan, half the time is needed for testing substances in the lifespan assay. Full article

Today, agriculture around the world is challenged by parasitic nematode infections. Plant-parasitic nematodes (PPNs) can cause significant damage and crop loss and are a threat to food security. For a long time, the management of PPN infection has relied on nematicides that impact not only parasitic nematodes but also other organisms. More recently, new nematicides have been developed that appear to specifically target PPN. Cyclobutrifluram belongs to this new category of nematicides. Using the nematode Caenorhabditis elegans as a model organism, we show here that cyclobutrifluram strongly impacts the survival and fertility rates of the worm by decreasing the number of germ cells. Furthermore, using a genetic approach, we demonstrate that cyclobutrifluram functions by inhibiting the mitochondrial succinate dehydrogenase (SDH) complex. Transcriptomic analysis revealed a strong response to cyclobutrifluram exposure. Among the deregulated genes, we found genes coding for detoxifying proteins, such as cytochrome P450s and UDP-glucuronosyl transferases (UGTs). Overall, our study contributes to the understanding of the molecular mode of action of cyclobutrifluram, to the finding of new approaches against nematicide resistance, and to the discovery of novel nematicides. Furthermore, this study confirms that C. elegans is a suitable model organism to study the mode of action of nematicides. Full article