👤 Elisabetta Mattioli

The metabolism of polyunsaturated fatty acids (PUFAs) plays an important role in male reproduction. Linoleic and alpha-linolenic acids need to be provided in the diet and they are converted into long chain polyunsaturated fatty acids by steps of elongation and desaturation, exerted by elongases 2 (ELOVL2) and 5 (ELOVL5) and Δ5- (FADS1) and Δ6-desaturase (FADS2). This study aims to assess the gene expression and localization of enzymes involved in the synthesis of n-3 and n-6 long-chain PUFAs in control rabbits and those fed diets containing 10% extruded flaxseed. Enzyme and PUFA localization were assessed in the testes and epididymis by immunofluorescence. Testes showed high gene expression of FADS2, ELOVL2 and ELOVL5 and low expression of FADS1. Intermediate metabolites, enzymes and final products were differently found in Leydig, Sertoli and germinal cells. FADS2 was localized in interstitial cells and elongated spermatids; ELOVL5 in meiotic cells; FADS1 was evident in interstitial tissue, Sertoli cells and elongated spermatids; ELOVL2 in interstitial cells. Epididymal vesicles were positive for FADS1, ELOVL2 and ELOVL5 as well as docosahexaenoic, eicosapentaenoic, and arachidonic acids. This knowledge of fatty acids (FA) metabolism in spermatogenesis and the influence of diet on FA profile could help identify causes of male infertility, suggesting new personalized therapy. Show less

Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P ≤ 10 The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia. Show less

Autosomal recessive mandibuloacral dysplasia [mandibuloacral dysplasia type A (MADA); Online Mendelian Inheritance in Man (OMIM) no. 248370] is caused by a mutation in LMNA encoding lamin A/C. Here we show that this mutation causes accumulation of the lamin A precursor protein, a marked alteration of the nuclear architecture and, hence, chromatin disorganization. Heterochromatin domains are altered or completely lost in MADA nuclei, consistent with the finding that heterochromatin-associated protein HP1beta and histone H3 methylated at lysine 9 and their nuclear envelope partner protein lamin B receptor (LBR) are delocalized and solubilized. Both accumulation of lamin A precursor and chromatin defects become more severe in older patients. These results strongly suggest that altered chromatin remodeling is a key event in the cascade of epigenetic events causing MADA and could be related to the premature-aging phenotype. Show less