Effect of apigenin on the reproductive system in male mice

Hui Li, Hong-Bo Li, Ming Zhang, Fang Yan, Zhong-Xian Zhang, Zhi-Lan Li

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DOI: 10.4236/health.2010.25065                

Abstract

This study aimed to characterize the effect of apigenin on the reproductive system in male mice. Adult male mice were treated with intraperitoneal injection of apigenin at the dose levels of 5, 10, 15, 20 and 25 mg/kg.bw, 0.05% DMSO and 0.9% normal saline daily for seven days. Then, testis and epididymis sperms in sperm motility, sperm morphology, the percentages of ploidy cells and seminiferous epithelium cells at the cell-circle phase, and the ratio of ploidy cells were evaluated. The results showed that sperm density significantly reduced in the 25 mg/kg group compared with the solvent control group. The abnormal sperms were mainly amorphous; non-hook sperms took the second largest group; and banana, double-tail and folded-tail sperms were rare. Abnormal sperms were mainly in the head sperm. Moreover, after intraperitoneal injection of 5 mg/kg apigenin, the percentage of 1C population increased, and the percentage of 4C declined, leading to a significant increase of the 1C:4C ratio, compared with the solvent and negative control groups. The percentage of seminiferous epithelium cells at the cell-circle phase of G0/G1 exhibited a significant increase in the 25 mg/kg group compared with the control groups. Taken together, that apigenin has adverse effects on the reproductive system in adult male mice is demonstrated.

Keywords

Apigenin; Male Mice;Intraperitoneal Injection; Sperm Motility;Sperm Morphology; Flow Cytometry

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Nelson, C.M.K. and Bunge, R.G. (1974) Semen analysis: Evidence for changing parameters of male fertility potential. Fertility and Sterility, 25(6), 503-507.
[2]	Carlsen, E., Giwereman, A., Keiding, N. and Skakkebaek, N.E. (1992) Evidence fordecreasing quality of semen during past 50 years. British Medical Journal, 305(6854), 609-613.
[3]	Sharpe, R.M. (1993) Declining sperm counts in men—is there an endocrine cause? Journal of Endocrinology, 136, 357-360.
[4]	Hertog, M.G., Hollman, P.C. and Katan, M.B. (1992) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. Journal of Agricultural and Food Chemistry, 40(12), 2379-2383.
[5]	Havsteen, B.H. (2002) The biochemistry and medicinal significance of the flavonoids. Pharmacology & Therapeutics, 96(2-3), 67-202.
[6]	Le Bail, J.C., Varnat, F., Nicolas, J.C. and Habrioux, G. (1998) Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Letters, 130(1), 209-216.
[7]	Breinholt, V.M., Offord, E.A., Brouwer, C., Nielsen, S.E., Brosen, K. and Friedberg, T. (2002) In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food and Chemical Toxicology, 40(5), 609- 616.
[8]	Havsteen, B.H. (2002) The biochemistry and medicinal significance of the flavonoids. Pharmacology & Therapeutics, 96(2-3), 67-202.
[9]	Breinholt, V., Hossaini, A., Svendsen, G.W., Brouwer, C. and Nielsen, E. (2000) Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability. Food and Chemical Toxicology, 38(7), 555-564.
[10]	Stroheker, T., Cabaton, N., Berges, R., Lamothe, V., Lhuguenot, J.C. and Chagnon, M.C. (2003) Influence of dietary soy isoflavones on the accessory sex organs of the Wistar rat. Food and Chemical Toxicology, 41(8), 1175-1183.
[11]	Birt, D.F., Hendrich, S. and Wang, W. (2001) Dietary agents in cancer prevention: Flavonoids and isoflavonoids. Pharmacology & Therapeutics, 90(2-3), 157-177.
[12]	Hiremath, S.P., Badami, S., Hunasagatta, S.K. and Patil, S.B. (2000) Antifertility and hormonal properties of flavones of Striga orobanchioides. European Journal of Pharmacology, 391(1-2), 193-197.
[13]	Miksicek, R.J. (1995) Estrogenic flavonoids: Structural requirements for biological activity. Proceedings of the Society for Experimental Biology and Medicine, 208(1), 44-50.
[14]	Dai, R., Jacobson, K.A., Robinson, R.C. and Friedman, F.K. (1997) Differential effects of flavonoids on testosterone-metabolizing cytochrome P450s. Life Sciences, 61, L75-L80.
[15]	Ibrahim, A.R. and Abul-Hajj, H.Y. (1990) Aromatase inhibition by flavonoids. Journal of Steroid Biochemistry and Molecular Biology, 37(2), 257-260.
[16]	Suschetet, M., Siess, M.H., Le Bon, A.M. and Canivenc- Lavier, M.C. (1998) Anticarcinogenic properties of some flavonoids, In: Vercauteren, J., Che`se, C. and Triaud, J. Eds., Polyphenols 96, INRA Editions, Versailles, 165- 204.
[17]	Wang, I.K., Lin-Shiau, S.Y. and Lin, J.K. (1999) Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukae mia HL-60 cells. European Journal of Cancer, 35(10), 1517-1525.
[18]	Huang, X. and Chen, X. (1985) Methodology of mutagenic, teratogenic and carcinogenic environmental chemicals, Zhejiang Science & Technology Press, Hangzhou, 64.
[19]	Perreault, S.D. (1997) The mature spermatozoa as a target for reproductive toxicants. In: Oekelheide, K., Chapin, R.E., Hoyer, P.B. and Harris, C., Eds., Comprehensive toxicology, Reproductive and Endocrine Toxicology, 10, 165-179.
[20]	Seed, J., Chapin, R.E., Clegg, E.D., Dostal, L.A., Foote, R.H., Hurtt, M.E., et al. (1996) Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report. Reproductive Toxicology, 10(3), 237-244.
[21]	Slott, V.L., Suarez, J.D. and Perreault, S.D. (1991) Rat sperm motility analysis: Methodologic considerations. Reproductive Toxicology, 5(5), 449-458.
[22]	Toth, G.P., Stober, J.A., George, E.L., Read, E.J. and Smith, M.K. (1991) Sources of variation in the computer-assisted motion analysis of rat epididymal sperm. Reproductive Toxicology, 5(6) 487-495.
[23]	Chapin, R.E., Filler, R.S., Gulati, D., Heindel, J.J., Katz, D.F., Mebus, C.A., et al. (1992) Methods for assessing rat sperm motility. Reproductive Toxicology, 6(3), 267- 273.
[24]	Slott, V.L., Suarez, J.D., Poss, P.M., Linder, R.E., Strader, L.F. and Perreault, S.D. (1993) Optimization of the Hamilton-Thorn computerized sperm motility analysis system for use with rat spermatozoa in toxicological studies. Fundamental and Applied Toxicology, 21(3), 298-307.
[25]	Slott, V.L., Linder, R.E. and Dyer, C.J. (1994) Method of euthanasia does not affect sperm motility in the laboratory rat. Reproductive Toxicology, 8(4), 371-374.
[26]	Wier, P.J. and Rumberger, D. (1995) Isolation of rat sperm from the vas deferens for sperm motion analysis. Reproductive Toxicology, 9(3), 327-330.
[27]	Dostal, L.A., Faber, C.K. and Zandee, J. (1996) Sperm motion parameters in vas deferens and cauda epididymal rat sperm. Reproductive Toxicology, 10(3), 231-235.
[28]	Pu, Y., Li, Z., Zhao, J., Wang, X., Dang, Y. and An, J. (2007) The experimental study on the effect of celery on sperm quality in mice. Health Vocational Education, 25, 122-124.
[29]	Wang, H., Meng, Z. and Chang, F. (2006) The toxic effects of in vivo derivatives of sulfur dioxide on sperms in male mice. Journal of Application and Environmental Biology, 12, 363-366.
[30]	Petim, J.M., Ratinaud, M.H., Cordelli, E., Spano, M. and Julien, R. (1995) Mouse testis cell sorting according to DNA and mitochondrial changes during spermatogenesis. Cytometry, 19(4), 304-312.
[31]	Suter, L., Bechter, R., Koch, E. and Bohadilla, M. (1998) Three parameter flow cytometric analysis of rat spermatogenesis. Cytometry, 27(2), 161-168.
[32]	Spano, M., Baroleschi, C., Cordelli, E., Leter, G., Tiveron, C. and Pacchierotti, F. (1996) Flow cytometric assessment of trophosophamide toxicity on mouse spermatogenesis. Cytometry, 24, 174.