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Clinical and Experimental Obstetrics & Gynecology  2019, Vol. 46 Issue (3): 387-393    DOI: 10.12891/ceog4550.2019
Original Research Previous articles | Next articles
Effects of nicotine exposure on clomiphene citrate induced rats: morphological and immunohistochemical analysis in the ovaries
N. Karaca1, *(), Y.K. Akpak2, A. Cakır3, M. Marasli1, H. Aktun4
1Department of Obsterics and Gynaecology, School of Medicine, Bezmialem Vakif University, Istanbul, Turkey
2Department of Obstetrics and Gynaecology, Tepecik Training and Research Hospital, University of Health Sciences, Izmir
3Department of Pathology, School of Medicine, Medipol University Hospital, Istanbul, Turkey
4Department of Obsterics and Gynaecology, School of Medicine, Medipol University, Istanbul, Turkey
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Objective: The most common use of ovulation induction in clomiphene citrate (CC) administered rats is to investigate whether there is any morphologically and immunohistochemically difference in nicotine exposure between rats not exposed to nicotine and with no CC. Materials and Methods: A total of 24 healthy rats were randomly divided into three groups: Group 1 was the group that received transdermal nicotine patched followed by clomiphene citrate. Group 2 was the only intraperitoneally CC applied group. Group 3 was the normal saline administered intraperitoneally group. On the fourth day of the cycle animals were sacrificed and bilateral salpingo-oophorectomy was performed. Sections were taken and stained with standard haematoxylin for histopathological examination. For immunohistochemical evaluation, sections were stained with Ki-67 and CD34. Results: There were no significant differences between the groups in terms of ovarian follicular number and types, and follicle-stroma immunohistochemical staining Ki-67 expression. There was also no significant difference in the thickness of granulosa cell between the groups. However, among the groups, CD34 expressions in group 1 were statistically less in the secondary follicle (p = 0.000), corpus luteum (p = 0.012), and more in the ovarian stroma (p = 0.001). Conclusion: In the CC-stimulated animal model, the authors did not observe that transdermal nicotine exposure was morphologically deleterious to the follicular count and types. They also could not detect the thickness of granulosa cell. Perhaps the effect on over-stimulation with CC may be less than expected, depending on the route and dose of nicotine administered.

Key words:  Nicotine      Clomiphene citrate      Ki67 and CD34 expression      Ovulation induction     
Published:  10 June 2019     
*Corresponding Author(s):  N. KARACA     E-mail:

Cite this article: 

N. Karaca, Y.K. Akpak, A. Cakır, M. Marasli, H. Aktun. Effects of nicotine exposure on clomiphene citrate induced rats: morphological and immunohistochemical analysis in the ovaries. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(3): 387-393.

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