The effect of methoxychlor on IGF-I signaling pathway in rat ovary

Follicular development and ovarian functions are regulated by growth factors incluiding in IGF's. In addition, some foods and exogenic agents can also affect follicular development and ovarian function. One of the exogenic agents is MXC which is known endocrine disruptor. MXC which has estrogenic, antiestrogenic and antiandrogenic effects is a organochloride pesticid and it causes infertility in female by changing many reproductive parameters and ovarian functions. In this study, our aim is to detect how MXC effects proportional distribution of the follicle stages in adult rats after MXC treatment (100 mg/kg/day) between embryonal (E)18- postanatal day (PND) 7, and also determine stage specific IGF-I and IGF-IR expressions in ovarian follicles and relationship between follicular development and the levels of IGF-I and IGF-IR expression, and investigate if MXC changes levels of IGF-I and IGF-IR protein in ovary. An increase in secondary, preantral follicles (p<0,01) and a decrease in primordial and antral follicles (p<0,05 ) were detected in follicular composition. IGF-I expression in oocyte and granlosa cells of follicles, and the luteal and interstitial cells, theca externa and interna and also smooth muscle of ovary vessels were showed by using immunohistochemical staining. IGF-IR was expressed in same localizations with IGF-I in ovary except for theca externa. An increase in both IGF-I and IGF-IR expressions were indicated during follicular development. It was observed that MXC treatment decreased IGF-I expression in preantral and antral follicles (p<0,05) and increased IGF-IR expression in oocytes of secondary follicles and granulosa cells of secondary and preantral follicles (p<0,05). In conclusion, MXC exposure to fetal and neonatal rats causes morphological and molecular alterations in adult ovary. MXC changes stage specific IGF-I and IGF-IR expressions in ovarian follicles, accordingly some differences can be seen in follicular composition of MXC treatment group when compared to that of control group. IGF signal pathway may be a significant role in MXC induced ovary disfunction and female infertility. Key Words: Endocrine Disruptors, IGF-I, IGF-IR, Methoxychlor, Ra