Effect of genistein administration on the recovery of spermatogenesis in the busulfan-treated rat testis

Abstract

ObjectiveImpairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan.MethodsBusulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally.ResultsThe weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group.ConclusionGenistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.

β-carotene Rescues Busulfan Disrupted Spermatogenesis Through Elevation in Testicular Antioxidant Capability

“…In current investigation, 1∼300 mg/kg β-carotene was used with or without busulfan for dosing mice, we found that busulfan (single dose 40 mg/kg BW at 3 weeks of age) resulted in azoospermia in mice during adulthood (8 weeks of age). The result was consistent with lots of previous reports ( Chi et al, 2013 ; Jung et al, 2015 ; Liu et al, 2019 ). Moreover, β-carotene increased sperm concentration and motility after busulfan treatment.…”

“…Many investigations have attempted to improve spermatogenesis and male fertility using a busulfan treated animal model. Busulfan can cause azoospermia by destroying testicular germ cells and increasing sperm abnormalities ( Chi et al, 2013 ; Jung et al, 2015 ; Liu et al, 2019 ). It has been reported that molybdenum (Mo) rescued mouse spermatogenesis by the improvement of male germ cell development s, and maintaining of blood hormone levels (testosterone, estradiol, and luteinizing hormone) ( Liu et al, 2019 ).…”

“…Korean red ginseng can rescue busulfan induced the disruption of spermatogenesis ( Jung et al, 2015 ). Genistein has been reported to decrease intra-testicular testosterone (ITT) level and to rescue busulfan disrupted spermatogenesis in rats ( Chi et al, 2013 ). Furthermore, Zhao et al (2020) found that alginate oligosaccharides (AOS) improved busulfan disrupted spermatogenesis at the single cell level.…”

Intra-Testicular Signals Regulate Germ Cell Progression and Production of Qualitatively Mature Spermatozoa in Vertebrates

“…However, gynecomastia and cardiovascular problems are secondary effects related to E 2 treatment and represent the major impediment to clinical application. Recently, it has been suggested that the phytoestrogen genistein may be a true substitute for E 2 ( 135 ).…”

Genistein up-regulates miR-20a to disrupt spermatogenesis via targeting Limk1

“…In 2014, Jones et al, [ 26 ] demonstrated that simultaneous gestational exposure to GEN and DEHP induced long-term alterations in testis development and function. Besides, GEN has also been reported to mitigate radiation-induced testicular damage in male C3H/HeN mice with 200 mg/kg body weight administration [ 27 ] as well as recover spermatogenesis in the busulfan-treated rat testis orally daily at a dose of either 50 or 100 mg/kg [ 28 ]. In our present study, we found that ICR mice orally at a dose of 5 mg/kg/day for 35 days could induce abnormal spermatogenesis to some extent, mainly on mice VAP, VSL and VCL.…”