Histometrical study of ovarian follicles of immature mice treated with methylphenidate

Authors

1 Department of Anatomy, Tehran Medical Sciences Branch, Islamic Azad University, Tehran-Iran

2 Department of Ophtalmology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran-Iran

3 Department of Basic Sciences, Faculty of Veterrinary Medicine, University of Tehran, Tehran-Iran

4 Department of Pediatrics, University of Medical Sciences, Zanjan-Iran

Abstract

BACKGROUND: The main part of ovary is consisted of follicles which certain drugs may cause change in them. OBJECTIVES: The purpose of this study was to investigate the effects of Methylphenidate on ovarian follicle of mice, treated by Ritalin before puberty. METHODS: 40 immature female mice at 3 weeks of age were divided into 4 groups, consisting of one control and 3 experimental groups. The experimental groups were gavaged by 2, 5 and 10 mg/kg methylphenidate respectively and the control group received only distilled water with the same method for 60 days. At the end of the experiment, the mice were weighed and then the serum levels of FSH and LH were assessed and structural changes of ovarian follicles and corpora lutea were studied. RESULTS: The mean difference of body weight in experimental groups compared with the control group which showed a significant reduction (p<0.05). In experimental groups compared with the control group, a significant reduction in pre enteral, enteral follicles, corpora lutea and a significant increase in atretic follicles were observed (p<0.05). CONCLUSIONS: Ritalin intake for a long period may increase the number of atretic follicles and decrease corpora lutea, so subsequently results in reduction of the growth of follicles and oocytes as well as inducing the atypical appearance of the cells in the luteinized cells.

Keywords

References

Ayalon, D., Nir, I., Cordova, T., Bauminger, S., Puder, M., Naor, Z., Kashi, R., Zor, U., Harell, A., Lindner, H.R. (1977) Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat. Neuroendocrinology. 42: 23-31.
Bolon, B., Bucc, T.J., Warbritton, A.R., Chen, J.J., Mattison, D.R., Heindel, J.J. (1997) Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: results from continuous breeding bioassays. Fundam Appl Toxicol. 39: 1-10.
Brit, K.L., Drummond, A.E., Cox, V.A., Dyson, M., Wreford, N.G., Jones, M.E. (2000) An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene Endocrinol. 141: 2614-2623.  
Chatterjee-Chakrabarty, S., Miller, B.T., Collins, T.J., Nagamani, M. (2005) Adverse effects of methylphenidate on the reproductive axis of adolescent female rats. Fertil Steril. 84: 1131-1138.
Clark, A.S., 5Kelton ,M.C., Whitney, A.C. (2003) (Chronic administration of anabolic steroids disrupts pubertal onset and estrous cyclicity in rats. Biol Reprod. 68: 465-471.
Elvin, J.A., Yan, C., Wang, P., 5Nishimori, K., Matzuk, M.M. (1999) Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Mol Endocrinol. 13: 1018-1034.
Gerschenson, M., Paik, C.Y., Gaukler, E.L., Diwan, B.A., Poirier, M.C. (2001) Cisplatin exposure induces mitochondrial toxicity in pregnant rats and their fetuses. Reprod Toxicol. 15: 525–531.
Himelstein-Braw, R., Byskov, A.G., Peters, H., Faber, M. (1976) Follicular atresia in the infant human ovary. Reprod Fertil. 46: 55-59.
Hoak, D.C., Schwartz, N.B. (1980) Blockade of recruitment of ovarian follicles by suppression of the secondary surge of follicle-stimulating hormone with porcine follicular field. PNAS. 77: 4953–4956.
Holtkamp, K., Wallraf, B., 5Wüller, S.R., 5Herpertz-Dahlmann, B. (2002) Methylphenidate-related growth impairment. J Child Adolesc Psychopharmacol. 12: 55-61.
Kurahashi, N., Kondo, T., Omura, M., Umemura, T., Ma, M., Kishi, R. (2005) The effects of subacute inhalation of di [2-ethylhexyl] phthalate (DEHP) on the testes of prepubertal Wistar rats. J Occup Health. 47: 437-444.
Lisska, M.C., Rivkees, S.A. (2003) Daily methylphenidate use slows the growth of children: a community based study. J Pediatr Endocrinol Metab. 16: 711-718.
Ludolph, A.G., Schaz, U., Storch, A., Liebau, S., Fegert, J.M., Boeckers, T.M. (2006) Methylphenidate exerts no neurotoxic, but neuroprotective effects in vitro. J Neural Transm. 113: 1927-1934.
Manjanatha, M.G., Shelton, S.D., Dobrovolsky, V.N., Shaddock, J.G., McGarrity, L.G., Doerge, D.R., Twaddle NW, Lin CJ, Chen JJ, Mattison DR, Morris SM. (2008) Pharmacokinetic,dose-range,and mutagenecity studies of methylphenidate hydrochloride in B6C3F1 mice. Environ Mol Mutagen. 49: 585-593.
Meller, W.H., Grambsch, P.L., Bingham, C., Tagatz, G.E. (2001) Hypothalamic pituitary gonadal axis dysregulation in depressed women. Psychoneuroendocrinology. 26: 253-259.
Moll, G.H., Hause, S., Rüther, E., Rothenberger, A., Huether, G. (2001) Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters. J Child Adolesc Psychopharmacol.   11: 15-24.
Myers, M.,  Britt, K.L., Ebling, F.J.P., %Kerr, J.B. (2004) Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 127: 569-580.
Schenk, J.O. (2002) The functioning neuronal transporter for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate. Prog Drug Res. 59: 111-131.
Thomas, P. (1990) Teleost model for studying the effects of chemicals on female reproductive endocrine function. Exp Zool. 256: 126–128.
Volkow, N.D., Ding, Y.S., Fowler, J.S., Wang, G.J., Logan, J, , J.S., Dewey, S., Ashby, C., Liebermann, J., 5Hitzemann, R. (1995) Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry. 52: 456-563.
Volkow, N.D., Fowler, J.S., Wang, G., Ding, Y., Gatley, S.J. (2002)  Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord. 6: 31-43.
Journal of Veterinary Research
Volume 70, Issue 3 - Serial Number 3
September 2015
Pages 301-307

Files

Share

How to cite

Statistics