Fluoride Interferes with the Sperm Fertilizing Ability via Downregulated SPAM1, ACR, and PRSS21 Expression in Rat Epididymis

Abstract

Fluoride is a widespread environmental pollutant that can induce low sperm quality and fertilizing ability; however, the underlying mechanism still remains unclear. Hence, we aimed to investigate the influence of fluoride on the sperm fertilizing ability via some key proteins in the epididymis. For this, 40 adult rats were assigned randomly into four groups. The control group was given distilled water, while the other three groups were given 25, 50, and 100 mg of NaF/L via drinking water for 56 days, respectively. After 1 day, epididymides were processed for sperm–egg binding, RNA extraction, western blot, and immunofluorescence analysis. Fluoride exposure reduced the ability of sperm to break down the egg cumulus cell layer. A further study revealed that fluoride altered the expression levels of genes and proteins related to acrosome reaction in vivo, including SPAM1, ACR, and PRSS21. However, fluoride only affected the expression of the ACR protein only in the epididymis but not in the testis. Fluoride also affected the expression levels of the membrane proteins CD9 and CD81 of epididymosomes in the epididymis. From the results, it can be concluded that fluoride exposure reduced the ability of sperm to break down the egg cumulus cell layer, which could be one of the reasons for decreased fertility ability in males treated with fluoride. These results provide some theoretical guidance and new ideas for treatments of low fertility, infertility, and other reproductive diseases.

IL-17A deficiency alleviate fluoride-induced injury by inhibiting immune response and apoptosis in testis

“…In our study, the use of different genotype animal models of uorosis revealed that excessive NaF intake in the testes of WT mice could induce sperm count reduction and increase the rate of abnormal spermatozoa. In addition, it was found that the distance between seminiferous tubules increased and the number of cells in spermatozoa and stroma decreased in testis of uorosis mice [19]. However, IL-17A de cient mice treated with 50 mg/L NaF for 90 days could effectively suppress these abnormal changes of semen quality and structure.…”

Molecular perspective concerning fluoride and arsenic mediated disorders on epididymal maturation of spermatozoa: A concise review

“…54 Recent report also revealed that fluoride downregulates the expression of SPAM1, CD9 and CD81 proteins in entire cauda epididymis, which cause obstruction of the sperm maturation and as well as inhibition of sperm egg binding. 46 This study has revealed that spermatozoa deficient with ACR protein show decreased progressive motility toward the cumulus cells than wild type spermatozoa and PRSS21 disrupted spermatozoa exhibit fragile neck in addition to slower motility rate. The study further states that fluoride exposure down-regulates both mRNA and protein expression of ACR and PRSS21 protein in cauda epididymis 46 and this might be one possible mechanism by which fluoride affects spermatozoal progressive motility and fertilizing ability.…”

“…45 Beside these proteins, SPAM1 protein, secreted from epididymal epithelial cells is incorporated in spermatozoal head through epididymosome and this protein helps to break the cumulus layer of egg. 46 Apart from SPAM1, Other two proteins serine protease PRSS21 and acrosin (ACR) play pivotal role in fertilization process by promoting spermatozoal motility and acrosome reaction. 46 Other transmembrane proteins, CD9 and CD81, which also represent epididymosome and promote signal transduction.…”

“…46 Apart from SPAM1, Other two proteins serine protease PRSS21 and acrosin (ACR) play pivotal role in fertilization process by promoting spermatozoal motility and acrosome reaction. 46 Other transmembrane proteins, CD9 and CD81, which also represent epididymosome and promote signal transduction. MFGE8 is also present in epididymosome and is responsible for maturation of spermatozoa.…”

Quercetin Affects Spermatogenesis-Related Genes of Mouse Exposed to High-Cholesterol Diet

“…Adam29 is also involved in sperm-oocyte interaction, and reduced expression of Adam29 is considered a potential indicator of male infertility (Schiza et al, 2019). Therefore, SPAM1, ADAM5, and ADAM29 are considered molecular markers of sperm maturation and sperm fertilizing ability (Jaiswal et al, 2015;Liu et al, 2019). SRD5A1 and SRD5A2 belong to the steroid 5α-reductase family and are responsible for producing dihydrotestosterone, a derivative of testosterone (Saartok et al, 1984).…”