Studies On The Alteration Of Whole Genome Level In Testicles Development Of SD Rats Induced By Linuron

Objective:To explore the reproductive toxicity mechanism of linuron on Fl male ratsMethod:Pregnant female rats were exposed to linuron (linuron was dissolved to peanut oil in 24 mg/ml) at dose of 120 mg/kg (1.5ml) by body weight everyday during the period of gestation day(GD) 12 to 17. Meanwhile, the similar test of peanut oil explosure was set up, as the negative control. The three fetuses of each group were anatomized on gestation day 21. The total RNA was extracted from the testicle respectively and the whole genome microarray was hybridized to filter the differently expressing genes in the testicle from fetuses. Furthermore, the Gene Ontology and Pathway of the differently expressing genes were analyzed with DAVID software. After maturation, the semen from F1 male rats was analyzed, at the same time, we detected the tissue development of testicle, prostate, epididymis, spermatica from F1 male rats through HE stain and testicle through transmission electron microscopyResult:1. These experiments illustrated that compared to peanut oil explosure, the negative control group, there were 168 differently expressing genes in the testicle from the linuron explosure group, and 89 genes got up-regulated and 79 genes got down-regulated. There are some genes such as StAR, P450scc,3β-HSD, ABP,5a-R, Cox7a2 relating to T synthesis and some genes, c-myc, S6K, Apafl, TSC1 relating to cell proliferation and cell apoptosis. Biological process analysis of all of the differently expressing genes demostrated that 6 genes involved in the process of reproduction, and the Pathway analysis found that the products of the differently expressing genes participated in the PI3K, AMPK, insulin, mTOR signalling.2. Semen analysis showed that in the linuron explosure group, the number of sperm significantly decreased (P<0.01) and there was obvious malformation in the acrosome from the F1 male rats, compared to the peanut oil explosure group. There were some structural damage in seminiferous tubules, some spermatogenic cells and sperm overflowed and some plasma cells infiltrated in the testicle, furthermore, there were some cavity secretions accumulating and lumen expansion in spermatic cord tissue from the F1 male rats through HE staining. However, there were no obvious differences in prostate and epididymis between two group.Conclusion:Our results demonstrated that linuron inducing testicle development malformation, significant decrease of sperm and increase of sperm malformation in F1 male rats, could be through altering the expression of genes relating to testicle development and testosterone synthesis, as well as altering the PI3K and mTOR signaling pathway. Furthermore, combined with the results of gene chip and animal experiments, our research illustrated that besides as a kind of classic antiandrogen competing recptor with testosterone, linuron can serve its male reproductive toxicity via altering the expression of genes relating to synthesis of testosterone and dihydrotestosterone, as well as cell proliferation and cell apoptosis.