Front cover image for Effets de la consommation d'Allium Sativum sur les fonctions testiculaires chez le rat adulte : mise en évidence d'une altération des fonctions Leydigiennes et Sertoliennes et d'une apoptose des cellules germinales

Effets de la consommation d'Allium Sativum sur les fonctions testiculaires chez le rat adulte : mise en évidence d'une altération des fonctions Leydigiennes et Sertoliennes et d'une apoptose des cellules germinales

During these last decades, therapeutic effects of plants have taken attention of general public and of pharmaceutical firms looking for new active molecules. Numerous health benefits have been attributed to different plants such as garlic and serious experimentations are necessary to confirm them and also to investigate possible harmful secondary effects particularly to male fertility which was rarely studied. In this context we were interested by the effects of Allium sativum (As), or garlic, which is a frequently used plant in Mediterranean cooking with a growing therapeutic reputation due to its hypolipidaemic virtues. We tested the effects of different doses of crude garlic (5,10,15 and 30%) on various biochemical and molecular parameters of male fertility in adult rats. In the first part of the study, we showed that As modifies biochemical parameters of prostate and seminal vesicles without any effect on epididymis. Such consequences on accessory sexual glands could be linked to the decrease of testosterone production we observed after garlic treatment. Garlic effect was probably peripheral since LH serum levels (at 10-30% As) were increased and expression of enzymes implicated in steroid genesis was inhibited in Leydig cells. In the second part of this work, we showed that As induces an increased apoptosis of spermatocytes I (in pachytene stage) and of spermatids. Western blottings evidenced an increase in the expression of pro-apoptotic molecules - active caspase-3 and Smac/DIABLO- and of anti-apoptotic molecules -cIAP1 and cIAP2. Nevertheless, action of cIAPs was inhibited by Smac, so allowing caspase-3 apoptotic action on germ cells. Finally, As lead to a decrease in testosterone and FSH serum levels, these two hormones being known as regulators of Sertoli cell functions. As expression of Sertoli cell specific cytoskeleton tubulin-3 was not modified, it was argued that Sertoli cells number remained the same after garlic treatment as in control rats. Moreover, apoptosis was not detected in Sertoli cells using TUNEL technique and active caspase-3 immunodetection. But Sertoli cells functions may be affected by As treatment since some protein expressions were modified. AMH (whose production is controlled by testosterone and FSH) and p27kip (also controlled by testosterone) ARN levels were decreased at 10-30%As. On the other side, GATA4 expression was increased at 10-30%As. As GATA4 controls Star expression, it is possible that this transcription factor was increased in order to restore normal testosterone production by a paracrine interaction between Sertoli and Leydig cells. In conclusion, we identified adverse effects of crude garlic consumption on testis functions and evidenced some of its cellular and molecular mechanisms of action
Thesis, Dissertation, French, 2009