Ethnopharmacological communicationCynomorium songaricum induces spermatogenesis with glial cell-derived neurotrophic factor (GDNF) enhancement in rat testes
Graphical abstract
Cynomorium songaricum (CS) treatment induces sperm count and GDNF expression in rat testes. After 56 days of treatment with CS, the epididymal sperm counts were significantly higher than those in the control group. The testes of rats treated with CS exhibited a significant increase in GDNF mRNA levels compared to the control group, and Western blotting revealed a significant increase in the GDNF-immunoreactive band in CS-treated rats compared to the control group.
Introduction
The incidence rates of male infertility are increasing worldwide, the leading cause of which is low sperm count. It has been reported that sperm counts in Western countries have decreased by 1% annually over the last 50 years (Carlsen et al., 1992). Although there have been many clinical trials aim at improving the number and quality of sperm, they have met with only limited success. Recent studies on rats have indicated that male fertility, including sexual dysfunction, can be improved by medicinal herbs (Yeh et al., 2008).
Glial cell-derived neurotrophic factor (GDNF) is an important growth factor that facilitates communication between Sertoli cells and spermatogonia. GDNF induces the proliferation of undifferentiated spermatogonia under in vivo and in vitro conditions (Meng et al., 2000). In the testis, the GDNF dosage controls the cell fate of undifferentiated spermatogonia (Airaksinen and Saarma, 2002). Gene-targeted mice with one GDNF-null allele show partial depletion of spermatogenic stem cells, whereas those overexpressing GDNF show clusters of undifferentiated spermatogonia. GDNF stimulates DNA synthesis in spermatogonia (Viglietto et al., 2000).
Cynomorium songaricum (CS) is used in traditional Korean medicine as an herbal remedy for kidney and intestinal ailments, as well as impotence (Nickrent et al., 2005) which is a fleshy, monoecious or dioecious, holoparasitic herb that often produces swollen tuberous haustorial root connections to its host plants (Kuijt, 1969). Its chemical constituents include steroids, triterpenes, fructosides, flavonoids, and condensed tannins (Jiang et al., 2001). Several studies have examined the effects of CS extracts on mammalian reproductive cells. In addition, a water extract of CS induced a significant increase in sperm count, improved the percentage of live sperm and their motility, and decreased the number of abnormal sperm (Abdel-Rahman et al., 1999), and there was a marked increase in testicular weight in animals treated with the extracts, which also had a direct spermatogenic influence on the seminiferous tubules of immature rats, presumably by exerting a testosterone-like effect (Abdel-Magied et al., 2001).
However, the relationship between CS and its effects on male reproductive tract malfunction associated with GDNF gene expression and spermatogenesis in vivo have not been elucidated. To investigate the effects of CS on male reproductive system in rats, we performed sperm analysis, including testicular weight, sperm count, and sperm motility. In addition, we assessed GDNF expression at the mRNA and protein levels.
Section snippets
Preparation of CS extract
Cynomorii Herba is the dried fleshy stem of Cynomorium songaricum Ruprecht (Fam. Cynomoiaceae). CS, produced in China, was purchased from Wonkwang Herbal Dug Co. Ltd. (Seoul, Korea). A 300 g sample of dried CS was boiled in 6 L water at 100 °C for 2 h and the suspension was filtered. The filtrate was concentrated under reduced pressure and then lyophilised. The final yield was 26% (dry weight 76.60 g), and the sample was stored at 4 °C. A voucher specimen (SK003) was deposited in our laboratory.
Effects of CS on body and testicular weights
None of the animals died during the study and no noticeable adverse effects were observed in any of the animals after administration of the extract or vehicle. Rats treated with CS showed a slight change in body weight compared to the control group (429.2 ± 34.5 and 420.5 ± 26.9 g, respectively). The absolute weights of the testes of the CS-treated group were slightly but significantly greater than those of the control group (1.64 ± 0.05 and 1.52 ± 0.18 g, respectively; 7.89% increase, P < 0.05).
Effects of CS on sperm counts and sperm motility
After 56
Discussion and conclusion
Infertility is an increasing worldwide concern. The leading cause of male infertility is a low sperm count, and sperm counts in Western countries have decreased by 1% annually over the last 50 years (Carlsen et al., 1992). Although many clinical trials have been performed to improve the number and quality of sperm, they have had limited success. We believe that some medicinal herbs may improve male fertility with relatively few side effects.
CS has been used in traditional Korean medicine to
Acknowledgement
This research was supported by the Kyung Hee University Research Fund in 2008. (KHU-20081565)
References (15)
- et al.
The effect of aqueous extracts of Cynomorium coccineum and Withania somnifera on testicular development in immature Wistar rats
Journal of Ethnophamacology
(2001) - et al.
Disruption of murine Tenr results in teratospermia and male infertility
Developmental Biology
(2005) - et al.
Ginkgo biloba extract enhances male copulatory behavior and reduces serum prolactin levels in rats
Hormones and Behavior
(2008) - et al.
In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms
Journal of Ethnophamacology
(2005) - et al.
The effect of the aqueous extract of Cynomorium cocconieum on the epydidymal sperm pattern of the rat
Phytotherapy Research
(1999) - et al.
The GDNF family: signalling, biological functions and therapeutic value
Nature Reviews Neuroscience
(2002) Chinese Herbal Medicine
(1986)
Cited by (32)
Dietary folic acid supplementation improves semen quality and spermatogenesis through altering autophagy and histone methylation in the testis of aged broiler breeder roosters
2022, TheriogenologyCitation Excerpt :Similar results were obtained by Iman et al. [29] who showed that supplementation of FA improved spermatogenesis and semen quality in rats. To further investigate the effects of FA supplementation on the spermatogenesis of aged roosters, we examined the mRNA expression levels of spermatogenesis-related genes (CREM [38], PCK2 [39], DDX4 [40], and GDNF [41]). FA supplementation dramatically improved the mRNA expression levels of spermatogenesis-related genes.
Successful treatment of oligoasthenozoospermia using traditional Korean medicine resulting in spontaneous pregnancy: Two case reports
2016, Explore: The Journal of Science and HealingCitation Excerpt :A study has shown that the oligosaccharides from Morinda officinalis were a protective agent for the oxidative damaged sperm DNA.21 Epimedium koreanum Nakai had shown antioxidant activity,22 and Cynomorium songaricum Rupr showed significant increases in epididymal sperm count and absolute testes in rat testes.23 This effect might be a result of their antioxidative properties, which help restore the imbalance of excessive levels of ROS.
The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study
2016, European Journal of Integrative MedicineCitation Excerpt :Extracts of Epimedium koreanum Nakai had shown antioxidant activities, which included free radical- and ferric-reducing power and lipid peroxidation inhibition [24], and improved erectile function in aged rats [25]. Cynomorium songaricum Rupr showed significant increases in epididymal sperm counts and absolute testes in rat testes [26]. All of these effects might be a result of their antioxidative properties, which help restore the imbalance in excessive levels of ROS.
Yang-tonifying traditional Chinese medicinal plants and their potential phytoandrogenic activity
2014, Chinese Journal of Natural MedicinesChemical constituents and pharmacologic actions of cynomorium plants
2013, Chinese Journal of Natural Medicines