ABSTRACT
In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated. A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25â¯mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR. Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (-0.01⯱â¯0.24, -0.007⯱â¯0.52 vs. 1⯱â¯0.50, Pâ¯=â¯0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (-0.24⯱â¯2.28, -4.49⯱â¯4.86 vs. 1⯱â¯0.50, Pâ¯=â¯0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93⯱â¯0.17, 1.54⯱â¯0.17 vs. 0.51⯱â¯0.11; Pâ¯≤â¯0.000). The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.
Subject(s)
Calcium Channels/genetics , Mercuric Chloride/toxicity , Organometallic Compounds/toxicity , Seminal Plasma Proteins/genetics , Spermatozoa/drug effects , Testis/drug effects , Animals , Down-Regulation , Male , Mice , Sperm Motility/drug effects , Spermatozoa/metabolism , Testis/metabolism , Testis/pathologyABSTRACT
The present study examined survival- and growth-enhancing effects of cortical cells on basal forebrain cholinergic neurons (BFCNs) in culture and the degree to which endogenous nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) contribute to those trophic effects. When fetal (17 days of gestation) basal forebrain (BF) cells were grown for 5 days in coculture with cortical neurons, staining for acetylcholinesterase (AChE) showed a threefold increase in the number of BFCNs relative to BF cultures without cortex. Most of these labeled cells also displayed enhanced somatic, dendritic, and axonal growth. Coculturing cortical neurons with BF cells taken from postnatal animals produced similar results but with a somewhat greater degree of morphologic enhancement. Function-neutralizing antibodies to NGF, BDNF, and NT-3 were employed to determine whether they would block the trophic effects of cortical neurons on postnatal BFCNs. Although no significant changes in numbers or morphological features of AChE(+) neurons were observed with treatment with individual antibodies, cocultures treated with a combination of all three antibodies displayed fewer morphologically enhanced AChE(+) cells and more nonenhanced cells; the total number of AChE(+) neurons was not significantly changed. Treatment of pure BF cultures with exogenous NGF, BDNF, and NT-3 increased the number of AChE(+) neurons but did not reproduce the morphologic enhancement of cortical cells on BFCNs. These results suggest that neurotrophins by themselves can increase survival of postnatal BFCNs in culture and may work in concert with other unknown cortically derived factors to enhance BFCN morphologic differentiation. The unidentified cortical factors may also have strong survival-enhancing effects on BFCNs that are independent of the known neurotrophins.
