Novel hydrogen‐producing Si‐based agent reduces oxidative stress, and improves sperm motility and in vitro fertilization rate in varicocoele

Abstract

Background Varicocoele‐induced male infertility potentially involves oxidative stress. Although varicocoelectomy is recommended for varicocoele patients presenting abnormal semen findings, no pharmacotherapeutic methods currently exist. We have recently developed a silicon‐based agent that produces hydrogen by the reaction with water. Objectives This study aimed to investigate the therapeutic effects of oral administration of a Si‐based agent on varicocoele rat. Materials and methods Twenty‐one rats were divided into four groups: varicocoele + normal diet (n = 5), varicocoele + Si‐based agent‐supplemented diet (n = 6), sham + normal diet (n = 5), and sham + Si‐based agent‐supplemented diet (n = 5). All rats were euthanized four weeks after surgery. Results The mean left epididymal sperm motility was 74.4% in the sham group, 72.3% in the sham + Si group, 57.6% in the varicocoele group, and 66.9% in the varicocoele + Si group. Epididymal sperm motility was significantly lower in the varicocoele group, but was significantly higher upon Si‐based agent ingestion (P < .01). The mean left testicular weight, Johnsen's score, and left epididymal sperm concentration did not differ significantly between groups. The 8‐OHdG concentration and DNA fragmentation rate were significantly increased in the varicocoele group, but were significantly decreased in the Si‐based agent intake group (P < .01). Additionally, the IVF rate was significantly lower in the varicocoele group (26.3%) compared with the sham group (73.4%; P < .01), and was significantly higher in the varicocoele + Si group (51.8%) compared with the varicocoele group (P < .05), indicating that the Si‐based agent improves IVF rates. Discussion and conclusion Oral intake of the silicon‐based agent improves epididymal sperm motility and in vitro fertilization rates through hydrogen production and subsequent reduction of oxidative stress. Considering the lack of effective noninvasive methods, this Si‐based agent is potentially applicable for treating varicocoele‐induced abnormal semen parameters.

Visualization of Spatial Distribution of Spermatogenesis in Mouse Testes Using Creatine Chemical Exchange Saturation Transfer Imaging

“…Testicular tissues were examined using a Keyence BZ-X800 microscope (Keyence, Corporation, Osaka, Japan). For the histological evaluation of spermatogenesis, we evaluated at least 20 seminiferous tubules per testis using Johnsen's scoring system, 25,26 a 10-point evaluation method for quantifying spermatogenesis according to the profile of the cells encountered along the seminiferous tubules. A Johnsen score was evaluated by two urologists with more than 5 years of clinical experience (S.F.…”

Diverse Possibilities of Si-Based Agent, a Unique New Antioxidant

“…Since Si-based agents inhibit the increase in urinary 8-hydroxy-2-deoxyguanosine in renal disease [22,[35][36][37], these results indicate that Si-based agents eliminate various oxidative metabolites, especially lipid peroxides.…”

“…In rat models of kidney IR injury, the downregulation of the apoptotic signaling system was observed in the Si-based-agent-treated group compared to the non-treated group [37]. In fact, the Si-based agent alleviated renal IR injury, cell death in renal failure, and the fragmentation of sperm DNA in testicular varicose veins [22,[35][36][37]. Moreover, a Si-based agent suppressed cell death caused by IR injury during flap transplantation, resulting in a reduced flap necrosis area and the alleviation of flap injury [50].…”

Hydrogen Gas: A Novel Type of Antioxidant in Modulating Sexual Organs Homeostasis

“…Varicocele-induced male infertility potentially involves oxidative stress [ 87 ]. Recently, Inagaki developed a silicon-based agent that produces H 2 by the reaction with water [ 87 – 89 ]. By using this agent, they have investigated the therapeutic effects of H 2 on a varicocele rat model.…”

“…By using this agent, they have investigated the therapeutic effects of H 2 on a varicocele rat model. They found that oral intake of the silicon-based agent improves epididymal sperm motility and in vitro fertilization rates via H 2 production and subsequent reduction of oxidative stress [ 87 ]. The protective effect of H 2 on sperm was also confirmed in normal young and aged male mice.…”