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Biology subjects

Parry, L.

Publications and source records attributed to Parry, L..

5 recordsLinked to original sources

Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia

Preeclampsia is a major pregnancy complication driven by placental dysfunction, yet research is limited by reliance on patient-derived tissues and models that do not fully capture human disease. Here, we develop a genetically engineered human trophoblast organoid model of preeclampsia that can be generated without access to placental tissue. Using a CRISPR-based Prime Integrase strategy, we engineered induced trophoblast stem cells to express the preeclampsia-associated soluble fms-like tyrosine kinase-1 (sFlt-1) exon 15a isoform. Engineered organoids showed a transcriptional shift towards primary preeclamptic placentae and developed several features of disease. These included reduced PlGF, increased IL-6 and soluble endoglin, oxidative stress, impaired growth and an elevated sFlt-1/PlGF ratio comparable to primary preeclamptic trophoblast organoids. These broader changes were not reproduced by adding recombinant human sFlt-1 to control organoids. Conditioned media from engineered organoids impaired endothelial network formation, demonstrating a functional effect of the altered trophoblast secretome. Treatment with sulfasalazine and metformin also restored angiogenic balance and organoid growth. Together, these findings establish a tractable human model that reproduces molecular and functional features of preeclampsia and provides a platform to study disease mechanisms and test potential therapies.

cell biology↗

Combined interventions are required to reverse biodiversity and carbon losses in tropical forest frontiers

Halting deforestation and promoting restoration are at the core of biodiversity and climate strategies in tropical forest regions. Avoiding forest disturbances is also critically important but has received far less attention, and there is a lack of clarity about the cost-effectiveness of these three different interventions. We provide the first comparison of the biodiversity and carbon benefits and costs associated with each intervention, comparing observed and counterfactual outcomes based on in-depth field assessments and high-resolution remote sensing in Amazonian Brazil. Avoiding forest disturbances delivered the greatest benefits and was more cost-effective than either avoiding deforestation or restoration, with results being robust to a range of benefit and cost assumptions. However, combined interventions delivered the greatest gains and were essential to reverse biodiversity and carbon losses.

ecology↗

Identification of a specific set of genes predicting obesity before phenotype appearance

Obesity poses significant health and socioeconomic challenges, necessitating early detection of predisposition for effective personalized prevention. To identify candidate predictive markers, our study used two mouse models: one exhibiting interindividual variability in obesity predisposition and another inducing metabolic phenotypes through maternal nutritional stresses. In both cases, predisposition was assessed by challenging mice with a high-fat diet. Using multivariate analyses of transcriptomic data from white adipose tissue we identified a set of genes whose expression correlates with an elevated susceptibility to obesity. Importantly, the expression of these genes was impacted prior to the appearance of any symptoms. A prediction model, incorporating both mouse and publicly available human datasets, confirmed the discriminahve capacihes of our set of genes across species, sexes, and adipose hssue deposits. These genes are promising candidates to serve as diagnostic tools for identifying individuals at risk of obesity.

physiology↗

An early Cambrian polyp reveals an anemone-like ancestor for medusozoan cnidarians

Extant cnidarians are a disparate phylum of non-bilaterians and their diploblastic body plan represents a key step in animal evolution. Anthozoans (anemones, corals) are benthic polyps, while adult medusozoans (jellyfishes) are dominantly pelagic medusae. A sessile polyp is present in both groups and is widely conceived as the ancestral form of their last common ancestor. However, the nature and anatomy of this ancestral polyp, particularly of medusozoans, are controversial, owing to the divergent body plans of both groups in the extant lineages and the rarity of medusozoan soft tissues in the fossil record. Here we redescribe the enigmatic Conicula striata Luo et Hu from the early Cambrian Chengjiang biota, south China, which has previously been interpreted as a polyp, lophophorate or deuterostome. We show that C. striata possessed features of both anthozoans and medusozoans. Its stalked polyp and fully encasing conical, annulated organic skeleton (periderm) are features of medusozoans. However, the gut is partitioned by [~]28 mesenteries, and has a tubular pharynx, resembling anthozoans. Our phylogenetic analysis recovers C. striata as a stem medusozoan, indicating that the enormously diverse medusozoans were derived from an anemone-like ancestor, with the pharynx lost and number of mesenteries reduced prior to the origin of crown group Medusozoa.

paleontology↗

Maternal nutritional stress alters sperm competence in male mice offspring leading to reduced fertility

Infertility represents a growing burden worldwide, with one in seven couples presenting difficulties conceiving. Amongst these, 10-15% of the men have idiopathic infertility that does not correlate with any defect in the classical sperm parameters measured. In the present study, we used a mouse model to investigate the effects of maternal undernutrition on fertility in male progeny. Our results indicate that mothers fed on a low protein diet during gestation and lactation produce male offspring with normal sperm morphology, concentration and motility but exhibiting an overall decrease of fertility when they reach adulthood. Particularly, sperm from these offspring show a remarkable lower capacity to fertilize oocytes when copulation occurs early in the estrus cycle relative to ovulation, due to an altered sperm capacitation. Our data demonstrate for the first time that maternal nutritional stress can have long-term consequences on the reproductive health of male progeny by affecting sperm physiology, especially capacitation, with no observable impact on spermatogenesis and classical quantitative and qualitative sperm parameters. Moreover, our experimental model could be of major interest to study, explain, and ultimately treat certain categories of infertilities.

physiology↗