Skip to content
2000
Volume 22, Issue 2
  • ISSN: 1570-1638
  • E-ISSN: 1875-6220

Abstract

Background

(PG) is a plant that contains ginsenosides, which are considered adaptogens that confer cellular protection. However, the impact of PG on pituitary-ovarian dysfunction and subsequent infertility is unknown. This study investigated the hypothesis that PG would attenuate pituitary-ovarian dysfunction associated with mobile phone’s Radiofrequency Electromagnetic Radiation (RF-EMR) in experimental rat models and the possible involvement of a cAMP Response Element Modulator (CREM)-dependent pathway.

Methods

Twenty adult female Wistar rats were divided randomly into four groups, each consisting of five rats. The control group was administered a vehicle (distilled water) orally, while the group received 200 mg/kg of extract orally. The RF-EMR group was exposed to 900MHz radiation, and the RF-EMR + PG group was exposed to the same radiation while also being treated with 200 mg/kg of orally. These treatments were administered daily for a period of 56 days.

Results

The RF-EMR group exhibited significant reductions in serum levels of LH, FSH, estradiol, and progesterone compared to the control group. Moreover, levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were significantly lower in the RF-EMR group compared to the control. Additionally, there was a notable decrease in the expression of the CREM gene, accompanied by disrupted pituitary/ovarian morphology in the RF-EMR group compared to the control. However, the administration of PG mitigated these changes.

Conclusion

The findings of this study indicate that extract shields against pituitary-ovarian impairment linked to RF-EMR exposure from cell phones by boosting antioxidant capacity and promoting the CREM-dependent pathway.

Loading

Article metrics loading...

/content/journals/cddt/10.2174/0115701638279386240425050818
2024-04-30
2025-03-15
Loading full text...

Full text loading...

References

  1. BaanR. GrosseY. Lauby-SecretanB. El GhissassiF. BouvardV. Benbrahim-TallaaL. GuhaN. IslamiF. GalichetL. StraifK. WHO International Agency for Research on Cancer Monograph Working Group Carcinogenicity of radiofrequency electromagnetic fields.Lancet Oncol.201112762462610.1016/S1470‑2045(11)70147‑421845765
    [Google Scholar]
  2. VolkowN.D. TomasiD. WangG.J. VaskaP. FowlerJ.S. TelangF. AlexoffD. LoganJ. WongC. Effects of cell phone radiofrequency signal exposure on brain glucose metabolism.JAMA2011305880881310.1001/jama.2011.18621343580
    [Google Scholar]
  3. KesariK.K. KumarS. BehariJ. Effects of radiofrequency electromagnetic wave exposure from cellular phones on the reproductive pattern in male Wistar rats.Appl. Biochem. Biotechnol.2011164454655910.1007/s12010‑010‑9156‑021240569
    [Google Scholar]
  4. MerhiZ.O. Challenging cell phone impact on reproduction: A review.J. Assist. Reprod. Genet.201229429329710.1007/s10815‑012‑9722‑122350528
    [Google Scholar]
  5. BatellierF. CoutyI. PicardD. BrillardJ.P. Effects of exposing chicken eggs to a cell phone in “call” position over the entire incubation period.Theriogenology200869673774510.1016/j.theriogenology.2007.12.00618255134
    [Google Scholar]
  6. DiemE. SchwarzC. AdlkoferF. JahnO. RüdigerH. Non-thermal DNA breakage by mobile-phone radiation (1800MHz) in human fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro.Mutat. Res. Genet. Toxicol. Environ. Mutagen.2005583217818310.1016/j.mrgentox.2005.03.00615869902
    [Google Scholar]
  7. GulA. ÇelebiH. UğraşS. The effects of microwave emitted by cellular phones on ovarian follicles in rats.Arch. Gynecol. Obstet.2009280572973310.1007/s00404‑009‑0972‑919241083
    [Google Scholar]
  8. OralB. GuneyM. OzgunerF. KarahanN. MunganT. ComlekciS. CesurG. Endometrial apoptosis induced by a 900-MHz mobile phone: Preventive effects of vitamins E and C.Adv. Ther.200623695797310.1007/BF0285021717276964
    [Google Scholar]
  9. ZareenN. KhanM.Y. MinhasL.A. Dose related shifts in the developmental progress of chick embryos exposed to mobile phone induced electromagnetic fields.J. Ayub Med. Coll. Abbottabad200921113013420364761
    [Google Scholar]
  10. BortkiewiczA. Health effects of radiofrequency electromagnetic fields (RF EMF).Ind. Health201957440340510.2486/indhealth.57_40031378769
    [Google Scholar]
  11. PacchierottiF. ArdoinoL. BenassiB. ConsalesC. CordelliE. EleuteriP. MarinoC. SciortinoM. BrinkworthM.H. ChenG. McNameeJ.P. WoodA.W. HooijmansC.R. de VriesR.B.M. Effects of radiofrequency electromagnetic field (RF-EMF) exposure on male fertility and pregnancy and birth outcomes: Protocols for a systematic review of experimental studies in non-human mammals and in human sperm exposed in vitro.Environ. Int.202115710680610.1016/j.envint.2021.10680634454359
    [Google Scholar]
  12. BachH.V. KimJ. MyungS.K. ChoY.A. Efficacy of ginseng supplements on fatigue and physical performance: A meta-analysis.J. Korean Med. Sci.201631121879188610.3346/jkms.2016.31.12.187927822924
    [Google Scholar]
  13. ArringN.M. MillstineD. MarksL.A. NailL.M. Ginseng as a treatment for fatigue: A systematic review.J. Altern. Complement. Med.201824762463310.1089/acm.2017.036129624410
    [Google Scholar]
  14. LimK.H. LimD.J. KimJ.H. Ginsenoside-Re ameliorates ischemia and reperfusion injury in the heart: A hemodynamics approach.J. Ginseng Res.201337328329210.5142/jgr.2013.37.28324198653
    [Google Scholar]
  15. MancusoC SantangeloR Panax ginseng and Panax quinquefolius: From pharmacology to toxicology. Food Chem Toxicol2017107Pt A362372
    [Google Scholar]
  16. LiuH. LuX. HuY. FanX. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy.Pharmacol. Res.202016110526310.1016/j.phrs.2020.10526333127555
    [Google Scholar]
  17. SmithI. WilliamsonE.M. PutnamS. FarrimondJ. WhalleyB.J. Effects and mechanisms of ginseng and ginsenosides on cognition.Nutr. Rev.201472531933310.1111/nure.1209924666107
    [Google Scholar]
  18. ShinE.J. JoS. ChoiS. ChoC.W. LimW.C. HongH.D. LimT.G. JangY.J. JangM. ByunS. RheeY. Red ginseng improves exercise endurance by promoting mitochondrial biogenesis and myoblast differentiation.Molecules202025486510.3390/molecules2504086532079067
    [Google Scholar]
  19. HuangJ. LiuD. WangY. LiuL. LiJ. YuanJ. JiangZ. JiangZ. HsiaoW.L.W. LiuH. KhanI. XieY. WuJ. XieY. ZhangY. FuY. LiaoJ. WangW. LaiH. ShiA. CaiJ. LuoL. LiR. YaoX. FanX. WuQ. LiuZ. YanP. LuJ. YangM. WangL. CaoY. WeiH. LeungE.L.H. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy.Gut202271473474510.1136/gutjnl‑2020‑32103134006584
    [Google Scholar]
  20. KarmazynM. GanX.T. Ginseng for the treatment of diabetes and diabetes-related cardiovascular complications: A discussion of the evidence.Can. J. Physiol. Pharmacol.201997426527610.1139/cjpp‑2018‑044030395481
    [Google Scholar]
  21. BaikI.H. KimK.H. LeeK.A. Antioxidant, anti-inflammatory and antithrombotic effects of ginsenoside compound K enriched extract derived from ginseng sprouts.Molecules20212613410210.3390/molecules2613410234279442
    [Google Scholar]
  22. YiY.S. New mechanisms of ginseng saponin-mediated anti-inflammatory action via targeting canonical inflammasome signaling pathways.J. Ethnopharmacol.202127811429210.1016/j.jep.2021.11429234089812
    [Google Scholar]
  23. ShinK.O. SeoC.H. ChoH.H. OhS. HongS.P. YooH.S. HongJ.T. OhK.W. LeeY.M. Ginsenoside compound K inhibits angiogenesis via regulation of sphingosine kinase-1 in human umbilical vein endothelial cells.Arch. Pharm. Res.20143791183119210.1007/s12272‑014‑0340‑624687256
    [Google Scholar]
  24. OyewopoA.O. BadejogbinO.C. AjadiI.O. AturamuA. AjadiM.B. EbuwaI.V. AlebiosuI.A. AreloegbeS.E. OlaniyiK.S. Panax ginseng supplementation protects against testicular damage induced by radiofrequency electromagnetic radiation from cell phone.Nutrire20234824710.1186/s41110‑023‑00234‑7
    [Google Scholar]
  25. ShinK. GuoH. ChaY. BanY.H. SeoD.W. ChoiY. KimT.S. LeeS.P. KimJ.C. ChoiE.K. YonJ.M. KimY.B. Cereboost™, an American ginseng extract, improves cognitive function via up-regulation of choline acetyltransferase expression and neuroprotection.Regul. Toxicol. Pharmacol.201678535810.1016/j.yrtph.2016.04.00627112419
    [Google Scholar]
  26. LeeC.H. KimJ.H. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases.J. Ginseng Res.201438316116610.1016/j.jgr.2014.03.00125378989
    [Google Scholar]
  27. WonY.J. KimB. ShinY.K. JungS.H. YooS.K. HwangS.Y. SungJ.H. KimS.K. Pectinase-treated Panax ginseng extract (GINST) rescues testicular dysfunction in aged rats via redox-modulating proteins.Exp. Gerontol.201453576610.1016/j.exger.2014.02.01224594315
    [Google Scholar]
  28. GrayS.L. LackeyB.R. BooneW.R. Effects of Panax ginseng, zearalenol, and estradiol on sperm function.J. Ginseng Res.201640325125910.1016/j.jgr.2015.08.00427616901
    [Google Scholar]
  29. YuW.J. LeeB.J. NamS.Y. YangD.C. YunY.W. Modulating effects of Korean ginseng saponins on ovarian function in immature rats.Biol. Pharm. Bull.200326111574158010.1248/bpb.26.157414600404
    [Google Scholar]
  30. LeeS.R. KimM.R. YonJ.M. BaekI.J. LeeB.J. AhnB. KimY.B. KwackS.J. LeeR.D. KimS.S. ChoD.H. HurG.H. YunY.W. NamS.Y. Effects of ginsenosides on organogenesis and expression of glutathione peroxidase genes in cultured rat embryos.J. Reprod. Dev.200854316417010.1262/jrd.1915218305367
    [Google Scholar]
  31. YunB.H. ChoiY.S. ChoS. LeeB.S. KimS.K. SeoS.K. Effects of ginseng on fertility.Biomed. J. Sci. Tech. Res.201811182348237
    [Google Scholar]
  32. MinegishiT. TanoM. ShinozakiH. NakamuraK. AbeY. IbukiY. MiyamotoK. Dual coupling and down regulation of human FSH receptor in CHO cells.Life Sci.199760232043205010.1016/S0024‑3205(97)00191‑49180358
    [Google Scholar]
  33. KaprioH. HeuserV.D. OrteK. TukiainenM. LeivoI. GardbergM. Expression of transcription factor CREM in human tissues.J. Histochem. Cytochem.202169849550910.1369/0022155421103200834261344
    [Google Scholar]
  34. Sánchez-JassoD.E. López-GuzmánS.F. Bermúdez-CruzR.M. OviedoN. Novel aspects of cAMP-response element modulator (CREM) role in spermatogenesis and male fertility.Int. J. Mol. Sci.202324161255810.3390/ijms24161255837628737
    [Google Scholar]
  35. FoulkesN.S. SchlotterF. PévetP. Sassone-CorsiP. Pituitary hormone FSH directs the CREM functional switch during spermatogenesis.Nature1993362641726426710.1038/362264a07681549
    [Google Scholar]
  36. ParkW.S. ShinD.Y. KimD.R. YangW.M. ChangM.S. ParkS.K. Korean ginseng induces spermatogenesis in rats through the activation of cAMP-responsive element modulator (CREM).Fertil. Steril.20078841000100210.1016/j.fertnstert.2006.12.01417418830
    [Google Scholar]
  37. Percie du SertN. AhluwaliaA. AlamS. AveyM.T. BakerM. BrowneW.J. ClarkA. CuthillI.C. DirnaglU. EmersonM. GarnerP. HolgateS.T. HowellsD.W. HurstV. KarpN.A. LazicS.E. LidsterK. MacCallumC.J. MacleodM. PearlE.J. PetersenO.H. RawleF. ReynoldsP. RooneyK. SenaE.S. SilberbergS.D. StecklerT. WürbelH. Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.PLoS Biol.2020187e300041110.1371/journal.pbio.300041132663221
    [Google Scholar]
  38. KopalliS.R. ChaK.M. RyuJ.H. LeeS.H. JeongM.S. HwangS.Y. LeeY.J. SongH.W. KimS.N. KimJ.C. KimS.K. Korean red ginseng improves testicular ineffectiveness in aging rats by modulating spermatogenesis-related molecules.Exp. Gerontol.201790263310.1016/j.exger.2017.01.02028126553
    [Google Scholar]
  39. EkpukO.W.O.H. Electromagnetic field levels associated with selected mobile phones.J. Int. Environ. Appl. Sci.20201526267
    [Google Scholar]
  40. NarayananS.N. KumarR.S. PotuB.K. NayakS. MailankotM. Spatial memory performance of Wistar rats exposed to mobile phone.Clinics200964323123410.1590/S1807‑5932200900030001419330250
    [Google Scholar]
  41. NarayananS.N. MohapatraN. JohnP. KN. KumarR.S. NayakS.B. BhatP.G. Radiofrequency electromagnetic radiation exposure effects on amygdala morphology, place preference behavior and brain caspase-3 activity in rats.Environ. Toxicol. Pharmacol.20185822022910.1016/j.etap.2018.01.00929413766
    [Google Scholar]
  42. OyewopoA. AdelekeO. JohnsonO. AkingbadeA. Quercetin upregulates CREM gene expression in cyanide-induced endocrine dysfunction.Heliyon202175e0690110.1016/j.heliyon.2021.e0690134027151
    [Google Scholar]
  43. MailankotM. KunnathA.P. JayalekshmiH. KoduruB. ValsalanR. Radio frequency electromagnetic radiation (RF-EMR) from GSM (0.9/1.8GHz) mobile phones induces oxidative stress and reduces sperm motility in rats.Clinics (São Paulo)200964656156510.1590/S1807‑5932200900060001119578660
    [Google Scholar]
  44. DesaiN. SharmaR. MakkerK. SabaneghE. AgarwalA. Physiologic and pathologic levels of reactive oxygen species in neat semen of infertile men.Fertil. Steril.20099251626163110.1016/j.fertnstert.2008.08.10918937945
    [Google Scholar]
  45. OtitolojuA.A. ObeI.A. AdewaleO.A. OtubanjoO.A. OsunkaluV.O. Preliminary study on the induction of sperm head abnormalities in mice, Mus musculus, exposed to radiofrequency radiations from global system for mobile communication base stations.Bull. Environ. Contam. Toxicol.2010841515410.1007/s00128‑009‑9894‑219816647
    [Google Scholar]
  46. KesariK.K. KumarS. BehariJ. Mobile phone usage and male infertility in Wistar rats.Indian J. Exp. Biol.2010481098799221299041
    [Google Scholar]
  47. GutschiT. Mohamad Al-AliB. ShamloulR. PummerK. TrummerH. Impact of cell phone use on men’s semen parameters.Andrologia201143531231610.1111/j.1439‑0272.2011.01075.x21951197
    [Google Scholar]
  48. LiJ. IchikawaT. JinY. HofsethL.J. NagarkattiP. NagarkattiM. WindustA. CuiT. An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions in cardiomyocytes.J. Ethnopharmacol.2010130222223010.1016/j.jep.2010.03.04020447451
    [Google Scholar]
  49. SohnS.H. KimS.K. KimY.O. KimH.D. ShinY.S. YangS.O. KimS.Y. LeeS.W. A comparison of antioxidant activity of Korean White and Red Ginsengs on H 2 O 2 -induced oxidative stress in HepG2 hepatoma cells.J. Ginseng Res.201337444245010.5142/jgr.2013.37.44224233437
    [Google Scholar]
  50. BakM.J. JunM. JeongW.S. Antioxidant and hepatoprotective effects of the red ginseng essential oil in H2O2-treated hepG2 cells and CCl(4)-treated mice.Int. J. Mol. Sci.20121322314233010.3390/ijms1302231422408456
    [Google Scholar]
  51. KesariK.K. AgarwalA. HenkelR. Radiations and male fertility.Reprod. Biol. Endocrinol.201816111810.1186/s12958‑018‑0431‑130445985
    [Google Scholar]
  52. BortkiewiczA. A study on the biological effects of exposure mobile-phone frequency EMF.Med. Pr.200152210110611761657
    [Google Scholar]
  53. SofikitisN. GiotitsasN. TsounapiP. BaltogiannisD. GiannakisD. PardalidisN. Hormonal regulation of spermatogenesis and spermiogenesis.J. Steroid Biochem. Mol. Biol.20081093-532333010.1016/j.jsbmb.2008.03.00418400489
    [Google Scholar]
  54. RezkA.Y. AbdulqawiK. MustafaR.M. Abo El-AzmT.M. Al-InanyH. Fetal and neonatal responses following maternal exposure to mobile phones.Saudi Med. J.200829221822318246230
    [Google Scholar]
  55. CelikO. HascalikS. Effect of electromagnetic field emitted by cellular phones on fetal heart rate patterns.Eur. J. Obstet. Gynecol. Reprod. Biol.20041121555610.1016/S0301‑2115(03)00288‑414687739
    [Google Scholar]
  56. OgawaK. NabaeK. WangJ. WakeK. WatanabeS. KawabeM. FujiwaraO. TakahashiS. IchiharaT. TamanoS. ShiraiT. Effects of gestational exposure to 1.95‐GHz W‐CDMA signals for IMT‐2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats.Bioelectromagnetics200930320521210.1002/bem.2045619194858
    [Google Scholar]
  57. TsaiS.C. ChiaoY.C. LuC.C. WangP.S. Stimulation of the secretion of luteinizing hormone by ginsenoside-Rb1 in male rats.Chin. J. Physiol.20034611712817698
    [Google Scholar]
  58. SalvatiG. GenovesiG. MarcelliniL. PaoliniP. De NuccioI. PepeM. ReM. Effects of Panax ginseng C.A. Meyer saponins on male fertility.Panminerva Med.19963842492549063034
    [Google Scholar]
  59. YoshimuraH. KimuraN. SugiuraK. Preventive effects of various ginseng saponins on the development of copulatory disorder induced by prolonged individual housing in male mice.Methods Find. Exp. Clin. Pharmacol.1998201596410.1358/mf.1998.20.1.4856339575484
    [Google Scholar]
  60. JungJ.H. ParkH.T. KimT. JeongM.J. LimS.C. NahS.Y. ChoI.H. ParkS.H. KangS.S. MoonC.J. KimJ.C. KimS.H. BaeC.S. Therapeutic effect of korean red ginseng extract on infertility caused by polycystic ovaries.J. Ginseng Res.201135225025510.5142/jgr.2011.35.2.25023717068
    [Google Scholar]
  61. ZhuL. LiJ. XingN. HanD. KuangH. GeP. American ginseng regulates gene expression to protect against premature ovarian failure in rats.BioMed Res. Int.201520151810.1155/2015/76712425705687
    [Google Scholar]
  62. FoulkesN.S. MellströmB. BenusiglioE. Sassone-CorsiP. Developmental switch of CREM function during spermatogenesis: from antagonist to activator.Nature19923556355808410.1038/355080a01370576
    [Google Scholar]
  63. YangW.M. ParkS.Y. KimH.M. ParkE.H. ParkS.K. ChangM.S. Effects of Panax ginseng on glial cell‐derived neurotrophic factor (GDNF) expression and spermatogenesis in rats.Phytother. Res.201125230831110.1002/ptr.323920625988
    [Google Scholar]
  64. StegerK. BehrR. KleinerI. WeinbauerG.F. BergmannM. Expression of activator of CREM in the testis (ACT) during normal and impaired spermatogenesis: Correlation with CREM expression.Mol. Hum. Reprod.200410212913510.1093/molehr/gah01214742698
    [Google Scholar]
  65. LeungK.W. WongA.S.T. Ginseng and male reproductive function.Spermatogenesis201333e2639110.4161/spmg.2639124381805
    [Google Scholar]
  66. ClemensJ.W. JaquelineK.M. AllistonT. RichardsJ.S. FitzpatrickS.L. SiroisJ. Ovarian cell differentiation: A cascade of multiple hormones, cellular signals, and regulated genes.Recent Prog Horm Res.19955022325410.1016/B978‑0‑12‑571150‑0.50014‑7
    [Google Scholar]
  67. LalliE. LeeJ.S. LamasM. TamaiK. ZazopoulosE. NantelF. PennaL. FoulkesN.S. Sassone-CorsiP. The nuclear response to cAMP: Role of transcription factor CREM.Philos. Trans. R. Soc. Lond. B Biol. Sci.1996351133620120910.1098/rstb.1996.00178650267
    [Google Scholar]
/content/journals/cddt/10.2174/0115701638279386240425050818
Loading
/content/journals/cddt/10.2174/0115701638279386240425050818
Loading

Data & Media loading...

Supplements

ARRIVE checklist is available as supplementary material on the publisher’s website along with the published article.


  • Article Type:
    Research Article
Keyword(s): Cell phone; CREM; electromagnetic radiation; ovary; Panax ginseng; pituitary gland
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test