Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study
نویسندگان
1 Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya
2 Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim, University, Buraydah, Saudi Arabia
3 Department of Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
4 Department of Gynecology and Obstetrics, School of Medicine, Zagazig University, Zagazig, Egypt
5 Department of Anatomy and Embryology, Faculty of Medicine, Alasmarya Islamic University, Zliten, Libya
6 Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
7 Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia
8 5. Department of Obstetrics and Gynecology, College of Medicine, Jouf University, Sakaka, Kingdom of Saudi Arabia
9 Department of Biology, College of Science, University of Jeddah, Jeddah, Kingdom of Saudi Arabia
10 Department of Histology and Cell Biology, School of Medicine, Tanta University, Tanta, Egypt
11 Department of Pathology, School of Medicine, Beni-Suef University, Beni-Suef, Egypt
doi
10.30476/ijms.2023.96905.2853چکیده
Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey’s post hoc test and Chi square test. P<0.05 was considered statistically significant.Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.
