Abstract
Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.
Highlights
Infertility, which can be explained as the failure of a couple in trying to conceive after one year of frequent, unprotected sexual intercourse, is a serious clinical issue that affects 13– 15% of couples worldwide [1]
We found that significant increases of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were exhibited in the treatment group compared with the control group by the second and fourth weeks (Figure 5(a))
There were no significant differences in Nrf2 and HO-1 mRNA in the control group across time points, but mRNA transcript levels were significantly higher in the treatment group compared with the control group by the second and fourth weeks (Figure 5(b))
Summary
Infertility, which can be explained as the failure of a couple in trying to conceive after one year of frequent, unprotected sexual intercourse, is a serious clinical issue that affects 13– 15% of couples worldwide [1]. Observation study on male infertility with oligozoospermia or azoospermia, in particular, suggests that some patients may have testicular heat exposure due to an intrinsic defect in scrotal thermoregulation, varicocele, or work hazard [3]. Several studies report that testicular hyperthermia above normal ranges causes impaired spermatogenesis due to heat-related oxidative stress on the seminiferous tubules [4, 5]. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in preventing the development of oxidative stress in spermatogenesis [6]. Decursin plays a major role as free radical scavenger and activated the upregulation of heme oxygenase (HO-1) expression through stimulation of Nrf, conferring protection against oxidative damage in rat pheochromocytoma (PC12) cells [11]. We hypothesized that decursin-induced HO-1 expression would protect against heat stress-induced degeneration of testicular germ cells and apoptosis
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