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      Korean Red Ginseng ( Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress–induced testicular damage in rats via multifunctional approach

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          Abstract

          Background

          Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress–induced testicular damage in experimental rats was evaluated.

          Methods

          Male rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 ± 1°C, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction.

          Results

          Significant ( p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly ( p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress–induced changes in rats significantly ( p < 0.05) at both concentrations.

          Conclusion

          KGC04P attenuated heat stress–induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility.

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          Most cited references47

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          Female subfertility.

          With an average monthly fecundity rate of only 20%, human beings are not fertile mammals. 10-15% of couples have difficulties conceiving, or conceiving the number of children they want, and seek specialist fertility care at least once during their reproductive lifetime. Dependent on the two main factors that determine subfertility, duration of childlessness and age of the woman, three questions need to be addressed before treatment is offered. Is it time to start the routine fertility investigation?--ie, has sufficient exposure to the chance of conception taken place? Are cost-effective, safe, and reliable treatments available for the disorder diagnosed? And, should the couple be referred straightaway for assisted reproduction?
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            Evidence for decreasing quality of semen during past 50 years.

            To investigate whether semen quality has changed during the past 50 years. Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). 14,947 men included in a total of 61 papers published between 1938 and 1991. Mean sperm density and mean seminal volume. Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
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              A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death.

              Spermatogenesis is a temperature-dependent process, and increases in scrotal temperature can disrupt its progression. We previously showed that heat stress causes DNA damage in germ cells, an increase in germ cell death (as seen on TUNEL staining), and subfertility. The present study evaluated the stress response in mouse testes following a single mild transient scrotal heat exposure (40 degrees C or 42 degrees C for 30 min). We investigated markers of three types of stress response, namely, hypoxia, oxidative stress, and apoptosis. Heat stress caused an increase in expression of hypoxia-inducible factor 1 alpha (Hif1a) mRNA expression and translocation of HIF1A protein to the germ cell nucleus, consistent with hypoxic stress. Increased expression of heme oxygenase 1 (Hmox1) and the antioxidant enzymes glutathione peroxidase 1 (GPX1) and glutathione S-transferase alpha (GSTA) was consistent with a robust oxidative stress response. Germ cell death was associated with an increase in expression of the effector caspase cleaved caspase 3 and a decrease in expression of the protein inhibitor of caspase-activated DNase (ICAD). Reduced expression of ICAD contributes to increased activity of caspase-activated DNase and is consistent with the increased rates of DNA fragmentation that have been detected previously using TUNEL staining. These studies confirmed that transient mild testicular hyperthermia results in temperature-dependent germ cell death and demonstrated that elevated temperature results in a complex stress response, including induction of genes associated with oxidative stress and hypoxia.
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                Author and article information

                Contributors
                Journal
                J Ginseng Res
                J Ginseng Res
                Journal of Ginseng Research
                Elsevier
                1226-8453
                2093-4947
                22 June 2018
                January 2019
                22 June 2018
                : 43
                : 1
                : 135-142
                Affiliations
                [1 ]Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea
                [2 ]Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea
                [3 ]Department of Biomedical Laboratory Science, College of Applied Science and Industry, Daejeon University, Daejeon, Republic of Korea
                Author notes
                []Corresponding author. Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Republic of Korea. skkim@ 123456kku.ac.kr
                [☆]

                Equally contributed to the study.

                Article
                S1226-8453(17)30382-2
                10.1016/j.jgr.2018.06.004
                6323164
                30662302
                e2d3e56c-7a03-4681-9dad-553dfb9f5bcd
                © 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 December 2017
                : 1 June 2018
                : 15 June 2018
                Categories
                Research Article

                antioxidants,heat stress,korean red ginseng,sex hormones,spermatogenesis

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