Clomiphene citrate impairs the endometrial CD98 expression in ovariectomized and non-ovariectomized rats: Role of HCG

Abstract

Background: Clomiphene citrate (CC) is one of the widely used drugs as an ovulation stimulant, but its adverse effects on the endometrium results in lowering down the pregnancy rate. Endometrium CD98 is also important in the process of implantation.

Objective: To evaluate the immunohistochemistry expression levels of endometrial CD98 following injection of CC with and without Human chorionic gonadotropin (HCG) in ovariectomized and non-ovariectomized rats.

Materials and methods: Seventy two (12-14 wk old) female Wistar rats were randomly divided into two groups (n = 36): (a) ovariectomized and (b) non-ovariectomized. Each group was further divided into six subgroups (n = 6/each): (1) CC 10 mg/kg, (2) CC 20 mg/kg, (3) HCG, (4) CC 10 mg/kg with HCG, (5) CC 20 mg/kg with HCG, and (6) control. The experimental subgroups received a single dose of CC (daily, five days) and HCG (after the last injection of CC) alone or in combination. Immunohistochemistry staining was performed on paraffin-embedded endometrial tissues to evaluate the expression levels of CD98.

Results: Animals undergoing ovariectomy presented a significantly lower expression level of endometrial CD98 (p $<$ 0.001) when compared with non-ovariectomized in the same condition that groups were subdivided. There was also a dose-dependent reduction (p $<$ 0.001) in the expression of CD98 in non-ovariectomized subgroups when compared with control group. In addition, injection of HCG following treatment with CC improved its expression.

Conclusion: It was concluded that CC impairs CD98 expression in endometrium and this impairment is intensified with the removal of the ovary. Also, an injection of HCG following treatment with CC can slightly improve the expression of CD98.

Keywords: CD98.; Clomiphene citrate; Human chorionic gonadotropin; Endometrium.

Figure 1

Microscopic images (10$\times$) of rat uterus tissues in different groups one day after mating; consider the expression levels due to chromogenic severity of the apex of endothelial cells. I. Ovariectomized subgroup: (a) CC10 group; (b) CC20 group; (c) CC10 + HCG group; (d) CC20 + HCG group; (e) HCG group; (control) Control group. II. Non-ovariectomized subgroup: (a') CC10 group; (b') CC20 group; (c') CC10 + HCG group; (d') CC20 + HCG group; (e') HCG group; (control') Control group.