Abstract
Mammalian spermatogenesis is a complex hormone-dependent developmental program where 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 for the Krabbe disease, characterized by the deficiency of galactosylceramidase (GALC), a lysosomal enzyme that hydrolyzes the terminal galactose from galactosylceramide, a typical component of the myelin membrane. In addition, GALC catalyzes the hydrolysis of the terminal galactose from galactosyl-alkyl-acyl-glycerol, precursor of seminolipids, specifically expressed on the membrane of germ cells. Previous data reported by our group demonstrated that glycolipids play an important role in sperm maturation and differentiation. Moreover, we hypothesized that the severe impairment of the central nervous system that affects the Twitcher mouse could interfere with the hypothalamus-pituitary-gonadal axis function, contributing to infertility. To highlight this hypothesis we have determined, at molecular level, the potential variation in expression pattern of brain hormones involved in spermatogenesis regulation.
Highlights
Infertility is a major medical problem worldwide
It is known that spermatogenesis in mammals requires the action of a complex assortment of peptides and hormones each of which plays an important role in the normal functioning of the seminiferous epithelium [6, 7]
luteinizing hormone (LH) stimulates the interstitial steroidogenic Leydig cells to produce testosterone, which has a local effect on interstitium and seminiferous tubules resulting in sperm production and maturation [9]
Summary
Infertility is a major medical problem worldwide. Male infertility affects 1 in 25 men in the Western world and is the cause of considerable social and financial burden [1]. FSH exerts its effect directly on the Sertoli cells whose direct contact with proliferating and differentiating germ cells within the seminiferous tubules makes them essential for providing both physical and nutritional support for spermatogenesis [10,11,12]. Testosterone and estradiol, the latter converted through aromatase in the testis interstitium as well as in germ cells [13], are direct negative feedback modulators of GnRH, LH, and FSH [14]. GALC is a lysosomal enzyme that hydrolyzes the terminal galactose from galactosylceramide, a typical component of the myelin membrane, and from galactosyl-alkyl-acyl-glycerol (GalAAG), precursor of seminolipids, glycolipids expressed on the membrane of germ cells www.frontiersin.org
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