Tubal cytokine changes accompany the epithelial atypia of letrozole-stimulated ovaries

Letrozole (LTZ), one of ovulation induction medications, is increasingly prescribed in many gynecological conditions. Although its hazardous effect on the ovarian surface epithelium (OSE) as well as tubal epithelium cells (TEC) has been previously studied, the associated changes occurring in the inflammatory cytokines have not been elucidated. Therefore, the objective of our study is to investigate these changes that may accompany LTZ-induced tubo-ovarian epithelial abnormalities. A total of 45 Sprague-Dawley rats were used in this study, divided equally into; control, LTZ6 and LTZ12 groups (received saline, 6 and 12 cycles LTZ i.p. respectively). Samples from ovaries (OVs) as well as fallopian tubes (FTs) were histologically studied for the associated changes. An increased proliferative activity, Ki67 immunoexpression and abnormal invaginations were observed in the OSE of LTZ6 group accompanied with occasional pseudostratification and loss of cilia of TEC. These changes became more pronounced in the LTZ12 where micropapillae, hyperchromasia, frequent deep invaginations, cysts of OSE as well as papillae and multilayering of TEC were noticed. The tubal level of IL-1β, IL-6, TNF-α and serum MCP-1 progressively increased in LTZ6 and LTZ12 groups compared with the control group. The significant positive correlation observed between these cytokines in the LTZ6 group became stronger in the LTZ12 one. However, no significant changes in the tubal IL-10 and TGF-β were detected. Therefore, further studies are required to consider these cytokines as objective markers to precisely assess severity of the associated epithelial changes particularly in long periods of stimulation.