Biology subjects

Farhat, W.

Publications and source records attributed to Farhat, W..

3 recordsLinked to original sources

bioRxiv2026

Sustained GnRH Agonism Alters Endocrine Dynamics and Pubertal Progression in Juvenile Rats

PurposeGonadotropin releasing hormone (GnRH) agonists are clinically used to delay pubertal progression by suppressing the hypothalamic-pituitary-gonadal (HPG) axis. While GnRH agonists have long been used clinically, the developmental characterization of HPG axis suppression during puberty remains incompletely understood. Thus, we examined the effects of GnRH receptor agonism in juvenile rats. HypothesisSustained GnRH receptor agonism will result in lower gonadal mass, blunt peripheral pubertal landmarks, and alter hormonal signaling dynamics within the HPG axis. MethodsAnimals received a single injection of extended-release leuprolide acetate depot (LA) or vehicle control on postnatal day (PND) 23. Animals were assessed for body mass and peripheral markers of puberty. On PND 44, animals were euthanized and tissues were evaluated to assess additional markers of pubertal maturation, pituitary gene transcript levels, and hormone concentrations in serum and gonads. ResultsIn females, LA treatment resulted in a smaller gonad size, increased body mass, and less vaginal openings. In males, LA treatment resulted in smaller gonads but did not significantly alter body mass or preputial separation. In the pituitary, LA-treated rats had lower Gnrhr, Fshb, and Lhb transcript levels regardless of sex, while females exhibited higher Cga and Nr5a1. Serum FSH and ACTH were lower in LA-treated animals, and treated females also had lower progestins and androstenedione, and higher LH. ConclusionsLA treatment reduced aspects of pubertal maturation and HPG axis output, with sex specific outcomes. These findings highlight the need for integrated, multi-level approaches to understand how altered GnRH signaling impacts pubertal and long-term physiology.

Developmental Biology↗

bioRxiv2026

A Multi-Omics Atlas of Naturally Occurring Myelomeningocele in a Large-Animal Model Reveals Heritable Architecture.

Neural tube closure relies on tightly coordinated morphogenetic programs integrating convergent extension, apical constriction of the neuroepithelium, and precise cell-cell interactions across germ layers. Disruption of these processes results in myelomeningocele, a severe complex congenital defect with lifelong multisystem consequences whose genetic and epigenetic determinants remain poorly defined. Using a sheep population with naturally occurring myelomeningocele, we quantified substantial heritability (0.42-0.68) and generated the first integrated multi-omics, multi-tissue atlas of this condition in any mammalian species. Genetic, transcriptomic, and whole-genome DNA methylation profiling across ectoderm- and mesoderm-derived tissues revealed shared and lineage-specific perturbations converging on cell-adhesion, cytoskeletal, migratory, inflammatory, and folate-responsive pathways. Chromosome 24 emerged as a multi-omics hotspot enriched for differentially expressed genes, differentially methylated regions, and candidate regulatory loci of GWAS signals, overlapping with human neurological and embryonic development trajectories. Cross-tissue network analyses highlighted coordinated disruption of neurulation-critical gene modules, establishing sheep as a robust translational model for mechanistic dissection of neural tube defect biology.

genetics↗

bioRxiv2021

Construction of functional biliary epithelial branched networks with predefined geometry using digital light stereolithography

Cholangiocytes, biliary epithelial cells, are known to spontaneously self-organize into spherical cysts with a central lumen. In this work, we explore a promising biocompatible stereolithographic approach to encapsulate cholangiocytes into geometrically-controlled 3D hydrogel structures to guide them towards the formation of branched tubular networks. We demonstrate that within the appropriate mix of hydrogels, normal rat cholangiocytes can proliferate, migrate and organize into branched tubular structures, form walls consisting of a cell monolayer, transport fluorescent dyes into the luminal space and show markers of epithelial maturation such as primary cilia. The resulting structures have dimensions typically found in the intralobular and intrahepatic bile ducts and are stable for weeks, without any requirement of bulk supporting material, thereby offering total access to the basal side of these biliary epithelial constructs.

bioengineering↗