Cells

Müllerian anomalies are anatomical variations of the female reproductive tract resulting from the incomplete development of the embryonic Müllerian ducts. The molecular mechanisms driving Müllerian duct development are complex and poorly understood, resulting in the largely unexplained aetiology of these conditions. WNT5A is a critical regulator of key developmental processes, including patterning, cell proliferation, and migration. Mutations of WNT5A have been associated with Robinow syndrome, a congenital condition characterized by skeletal and genital anomalies. In the mouse, WNT5A is necessary for the posterior development of the Müllerian duct, and ablation of Wnt5a results in vaginal agenesis. However, Wnt5a-/- uterine horns are hypoplastic and over 60% shorter than the wild type, suggesting specific functions in anterior Müllerian duct development. To better understand the role of Wnt5a, we performed single-cell RNA sequencing of developing Müllerian ducts. We found that the non-canonical Wnt PCP pathway was dysregulated in Wnt5a-/- mice. In addition, Wnt5a-/- Müllerian ducts were enriched in oviductal mesenchymal cells due to the transformation of the anterior uterine horns into oviducts. Our results indicate additional roles for Wnt5a during Müllerian duct development, prompting further investigations into uterine functions and anatomy in complex clinical cases of Müllerian anomalies including Robinow syndrome.

The miniature (mini) Ossabaw pigs are proposed as a translational preclinical model for testing and developing novel therapeutics for human diseases, including cystic fibrosis, cancer, and metabolic syndrome (MetS). In recent years, pigs have gained similar attention for studying retinal abnormalities and disorders owing to their close resemblance in size, anatomy, vasculature, and pathology to the human eye compared with their rodent counterparts. In our previous study, Ossabaw minipigs fed a Western diet for 10 weeks and followed for 3.5 months exhibited early signs of retinal degeneration and vascular abnormalities, mimicking the early stages of diabetic retinopathy (DR). To further evaluate pathomorphological alterations across neuronal and non-neuronal cell types, the present study comprehensively investigated individual retinal layers using cell-type-specific immunostaining. We found that the Western diet-fed mini pigs had reduced rhodopsin and blue opsins, changes in bipolar and ganglion cells, and reduced density of pre- and post-synaptic connections. Moreover, the retinas of obese mini pigs showed evidence of gliosis and microglial activation. Our findings suggest that a Western diet-induced metabolic disorder exhibits an early neurodegenerative milieu and further demonstrate the suitability of Ossabaw mini pigs as a model for human retinal diseases associated with MetS, such as DR and diabetic macular edema (DME).

Antiphospholipid syndrome (APS), first described in 1983, is a systemic autoimmune disorder characterized by recurrent arterial and venous thrombosis, pregnancy complications, and persistent antiphospholipid antibodies (aPL). Over four decades, significant advancements have been made in understanding APS pathogenesis, diagnostics, and treatment. Key discoveries include the development of standardized anticardiolipin antibody (aCL) assays, the identification of β2-glycoprotein I (β2GPI) as a critical cofactor, and the elucidation of the “two-hit” hypothesis, which explains thrombotic events through a combination of aPL-induced prothrombotic priming and secondary external triggers. Recent research has highlighted the roles of complement activation, neutrophil extracellular traps (NETs), and genetic predispositions shared with systemic lupus erythematosus (SLE). Innovations like the antiphospholipid score (aPL-S) and updated classification criteria, including the 2023 ACR/EULAR guidelines, have improved diagnostic precision and risk stratification. Despite these advances, challenges remain in assay standardization and addressing seronegative APS. Future directions emphasize the integration of multimodal biomarkers, precision diagnostics, and targeted therapies aimed at complement and NET pathways. These efforts aim to achieve individualized care, improving outcomes for APS patients through harmonized diagnostics, mechanistic therapeutics, and data-driven approaches. This review underscores the evolving understanding of APS and its potential for personalized management strategies.