Contribution à l’étude de l’impact d’un fongicide (Dithiocarbamate de manganèse : Manèbe) sur quelques paramètres de la fertilité masculine chez le lapin : Oryctolagus cuniculus

Ce travail vise à étudier l’effet d’un fongicide organométallique -le Manèbe- sur les paramètres de la fertilité chez le lapin male Oryctolagus cuniculus. Le fongicide a été appliqué a raison de deux doses: 1g /L et 2 g /L pendant 04 semaines successives. Les paramètres de fertilité y compris le poids testiculaire, quelques caractères biologiques des spermatozoïdes et le taux de la testostérone ont été étudiés. Les résultats révèlent qu’il y a une diminution significative dans le poids des testicules, la concentration et la mobilité des spermatozoïdes, et une augmentation significative dans les malformations morphologiques des spermatozoïdes chez les individus traités. D’autre part l’administration du Manèbe entraîne une diminution significative dans le taux de la testostérone.Mots-clés : Environnement, manèbe, lapin, fertilite - toxicite

The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin

Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT) mutation within exon 11 of LMNA, activating a splice donor site that results in production of a dominant negative form of lamin A protein, denoted progerin. Screening 150 skin biopsies from unaffected individuals (newborn to 97 years) showed that a similar splicing event occurs in vivo at a low level in the skin at all ages. While progerin mRNA remains low, the protein accumulates in the skin with age in a subset of dermal fibroblasts and in a few terminally differentiated keratinocytes. Progerin-positive fibroblasts localize near the basement membrane and in the papillary dermis of young adult skin; however, their numbers increase and their distribution reaches the deep reticular dermis in elderly skin. Our findings demonstrate that progerin expression is a biomarker of normal cellular aging and may potentially be linked to terminal differentiation and senescence in elderly individuals

Defective Lamin A-Rb Signaling in Hutchinson-Gilford Progeria Syndrome and Reversal by Farnesyltransferase Inhibition

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

Investigation of the activity of a family of fusion proteins that cause aggressive leukemia suggests transcriptional elongation as a new mechanism for oncogenic transformation