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Teratogenic and Embryotoxic Effects of Clomiphene Citrate in Developing Mice
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 Title & Authors
Teratogenic and Embryotoxic Effects of Clomiphene Citrate in Developing Mice
Ara, Chaman; Asmatullah, Asmatullah;
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The objective of this study was to assess the teratogenic and embryotoxic effects of clomiphene citrate in mice. The pregnant mice were administered a single dose of clomiphene citrate at different concentrations i.e 1.0, 2.0, 4.0 and 6.0 BW on day 8 of gestation. Fetuses recovered on day 18 of gestation were analyzed on morphological, morphometric and histological basis. Morphological observations showed defects like open eyelids, anophthalmia, fore and hindlimb micromelia, meromelia, amelia, sacral hygroma, hydrocephaly, hemorrhagic spots, kyphosis and clubbed feet. Morphometric analysis indicated a significant (p<0.001) reduction in fetal body weight, crown rump length, head circumference, eye circumference, forelimb and hindlimb lengths and tail size against controls. The histological observations showed brain defects like hydrocephaly, enlarged ventricles and undifferentiated neuroglial cells in cerebellum. Cleft palate, underdeveloped pharynx and atrophy of jaw muscles were the common anatomical defects of pharyngeal region. It is concluded that the concentrations of clomiphene citrate used during the present study proved teratogenic in mice fetuses.
Clomiphene Citrate;Teratogenicity;Embryotoxicity;Mice Development;
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Adashi, E. Y. 1993. Clomiphene citrate: the case of monoisomeric preparations. Baillieres. Clin. Obstet. Gynaecol. 7:331-347. crossref(new window)

Aker, H. and O. M. Bulay. 1985. Three Neon et al Ca Taract Cases produced in rats with clomiphene citrate. J. Med. Bes. 3(2): 185-188.

Alatas, C., E. Aksoy, B. Cenglz and M. Bahceci. 1995. Clomiphene citrate and phocomelia. Arch. Genaecol. Obstet. 256(1):33-34. crossref(new window)

Arriaga-Alba, M., R. Flores-Paz, R. Diaz-Hernandez and M. E. Gonzalez-Patino. 2001. Assesssment of genetic toxicity of the exposure of clomiphene citrate, with various bacterial test systems. Teratog. Carcing. Mutagen. 21(3):213-221. crossref(new window)

Asch, R. H. and R. B. Greenblatt. 1976. Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. J. Reprod. Med. 17(3):175-180.

Banhidy, F., N. Acs and A. E. Czeizel. 2008. Ovarian cysts, clomiphene therapy and the risk of neural tube defects. Int. J. Obstet. Genecol. 100(1):86-88. crossref(new window)

Bernstein, H. N. 1970. Some tatrogenic ocular diseases from systemically administered drugs. Int. Ophthalmol. Clin. 10: 553-618.

Brackett, N. L., M. Abae, O. D. Padron and C. M. Lynne. 1995. Treatment by assisted conception of severe male factor infertility due to spinal cord injury or other neurologic impairment. J. Assist. Reprod. Genet. 12(3):210-216. crossref(new window)

Casper, R. E. 2007. Aromatase inhibitors in ovarian stimulation. Steriod. Biochem. Mol. Biol. 106(1-5):71-75. crossref(new window)

Clark, J. H. and B. M. Markaverich. 1982. The agonistic-antagonistic properties of clomiphene: a review. Pharmacol. Therapeut. 15:467-519.

Csemiczky, G., J. Harlin and G. Fried. 2002. Predictive power of clomiphene citrate challenge test for failure of in vitro fertilization treatment. Acta. Obstet. Gynecol. Scand. 81(10): 954-961. crossref(new window)

CSGN. 2006. http:/

Deveci, E., H. S. Inaloz, S. S. Inaloz and B. Unal. 2000. Effect of clomiphene citrate on neonatal rat skin. Clin. Exp. Obstel. Gynecol. 27(3-4):238-240.

Dickey, R. P. and D. E. Holtkamp. 1996. Development, pharmacology and clinical experience with clomiphene citrate. Hum. Reprod. Update. 2(6):483-506. crossref(new window)

Duncan, D. B. 1955. Multiple range and multiple F tests. Biometrics 11:1-42. crossref(new window)

Dziadek, M. 2005. Preovulatory administration of clomiphene citrate to mice causes fetal growth retardation and neural tube defects (exencephaly) by an indirects maternal effect. Exp. Teratol. 47(4):263-273.

Elizur, S. E. and T. Tulandi. 2008. Drugs in fertility and fetal safety. Fertil. Steril. 89(6):1595-1602. crossref(new window)

ESHRE Capri Workshop Group, 1995. Anovulatory infertility. Hum. Reprod. 10:1549-1553. crossref(new window)

Haring, D. A. J. P., M. C. Cornel, J. C. Van der Linden, J. M. G. Van Vugt and M. L. Kwee. 2005. Acardius acephalus after induced ovulation: a case report. Clin. Teratol. 47(4):257-262.

Harmon, J. R., W. S. Branham and D. M. Sheehan. 2005. Transplacental estrogen responses in the fetal rat: Increased uterine weight and ornithine decarboxylase activity. Dev. Pharmacol. Toxicol. 39(3):253-260.

Kennedy, J. L. and E. Y. Adashi. 1987. Ovulation induction. Obstet. Gynecol. Clin. North Am. 14(4):831-864.

Lerner- Geva, L., L. Keinan-Boker, T. Blumstein, V. Boyko, L. Olmar, S. Mashiac, J. Rabinovici, G. Potashnick, E. Lunenfeld, J. G. Schenker, A. Shushan, A. Fishman, I. Cohen, I. Vagman and B. Lunenfeld. 2006. Infertility, ovulation induction treatments and the incidence of breast cancer-A historical prospective cohort of Israeli Women. Breast Cancer Res. Treat. 100(2):201-212. crossref(new window)

Macklon, N. S., R. L. Stoufer, L. C. Giudice and B. C. J. M. Fauser. 2006. The science behind 25 years of ovarian stimulationfor in vitro fertilization. Endocr. Rev. 27(2):170-207. crossref(new window)

Martikainen, H., L. Ronnberg, A. Roukonen and A. Kauppila. 2006. Effect of clomiphene citrate on prolactin and gonadotropin release during GnRH- analog treatment. Theriogenology 66(6-7):1560-1567. crossref(new window)

Mckenna, M. and R. J. Pepperell. 1988. Anti-oestrogens. Obstel. Gynaecol. 2:545-561.

Morris, J. M. 1970. Postcoital antifertility agents and their teratogenic effects. Contraception 2:85-97. crossref(new window)

Motta, C. M. and J. S. Hutchinson. 1991. Effects of clomiphene citrate on early pregnancy in guinea pigs. J. Reprod. Fertil. 92: 65-73. crossref(new window)

Orgeas, C. C., K. Sanner, P. Hall, P. Conner, J. Holte, S. J. Nilson, K. Sundfeldt, I. Persson, K. S. Chia, S. Wedron, P. W. Dickman and K. Czene. 2009. Breast cancer incident after hormonal treatment of infertility in Sweden: a cohort study. Am. J. Obstel. Gynecol. 200(1):72-77.

Plourde, P. V., H. E. Kulin and S. J. Santner. 1983. Clomiphene in treatment of adolescent gynacomastia: Clinical and endocrine studies. Am. J. Dis. Child. 137(11):1080-1082. crossref(new window)

Randal, J. M. and A. Templeton. 1991. The effects of clomiphene citrate upon ovulation and endocrinology when administered to patients with unexplained infertility. Hum. Reprod. 6(5):659-664.

Schardein, J. L. 1980. Congenital abnormalities and harmones during pregnancy: A clinical review. Clin. Teratol. 22(3):251-270. crossref(new window)