title: Morphological and molecular characterisation of Twitcher mouse spermatogenesis: an update.
abstract: Spermatogenesis is a complex developmental program in which interactions between different cell types are finely regulated. Mouse models in which any of the sperm maturation steps are perturbed provide major insights into the molecular control of spermatogenesis. The Twitcher mouse is a model of Krabbe disease, characterised by the deficiency of galactosylceramidase, the enzyme that hydrolyses galactosylceramide and galactosylsphingosine. Galactosyl-alkyl-acyl-glycerol, a precursor of seminolipid, the most abundant glycolipid in spermatozoa, is also a substrate for galactosylceramidase. Altered sphingolipid metabolism has been suggested to be the cause of the morphological abnormalities reported previously in the spermatogenesis of Twitcher. However, given the frequency of infertility associated with neurological impairment, we hypothesised that an unbalanced hormonal profile could contribute to male infertility in this mutant. In order to clarify this issue, we investigated potential variations in the expression of hormones and hormone receptors involved in the regulation of spermatogenesis. Our data show that, in the brain of Twitcher mouse, gonadotrophin-releasing hormone (GnRH), LH and FSH gene expression is decreased, whereas expression of androgen receptor (AR) and inhibin ßA (INHßA) is increased. The changes in gene expression for the LH and FSH receptors and AR in the testes support the hypothesis that altered sphingolipid metabolism is not the only cause of Twitcher infertility.
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Erica
authors: E
authors: Puggioni
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Laura
authors: L
authors: Governini
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Martina
authors: M
authors: Gori
authors: Department of Medicine, Surgery and Neuroscience, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Giuseppe
authors: G
authors: Belmonte
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Paola
authors: P
authors: Piomboni
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors: Elvira
authors: E
authors: Costantino-Ceccarini
authors: Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.|Corresponding author. Email: luddi@unisi.it.
authors: Alice
authors: A
authors: Luddi
keywords: Krabbe disease; gene expression