Abstract
Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.
Highlights
About 12% of reproductive-aged couples are suffering from infertility [1]
There was no significant difference between age, BMI, smoking and drinking between different groups while compared with Group 1
We found that in infertile male subjects, sperm motility was lower in relative higher GEN dose group (Group3) while the relative expression levels of seminal plasma miR-19b-1, miR-20a and miR92a-1 were higher in corresponding groups
Summary
About 12% of reproductive-aged couples are suffering from infertility [1]. Male infertility is defined as failure to father a child successfully after 12 months or more of regular intercourse [2]. Endocrine disrupting chemicals (EDCs) are some chemicals that may disrupt endogenous hormone to reduce adverse effects on immune response, development and reproduction in mammals [3]. As a class of EDCs, phytoestrogens (PEs) are natural plantderived non-steroidal compounds [4]. Because of their ability to mimic the structure of oestradiol, they can bind both estrogen receptors (ER-α and ER-β) [5]. Isoflavones, coumestans, naringin and lignans are four major classes of www.impactjournals.com/oncotarget
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