Presence of transforming growth factor alpha and epidermal growth factor in human ovarian tissue and follicular fluid

Intra-ovarian regulation of follicular maturation is modulated by various factors. Among these, growth factors are important local actors. We examined the immunohistochemical localization of transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in 18 human ovaries. The concentration of TGF-alpha and EGF in follicular fluid was measured by ELISA. TGF-alpha was detected in oocytes of primordial and early preantral follicles. Furthermore, staining was observed in granulosa cells of preantral follicles and in theca cells of preantral, antral and preovulatory follicles. EGF showed a similar distribution as TGF-alpha. Atretic follicles were strongly positive for TGF-alpha and EGF. In the corpus luteum, theca lutein cells were strongly positive for TGF-alpha and EGF. Immunoreactivity for EGF-R was observed only in the granulosa cells of antral follicles. Follicular fluids from patients undergoing in-vitro fertilization (IVF) were examined for their content of TGF-alpha and EGF. TGF-alpha was detected in 37% of the samples. The concentration ranged from 43 pg/ml to 602 pg/ml. EGF was not detected in any of the follicular fluids tested. These observations support the participation of EGF/TGF-alpha in follicular maturation. Furthermore, the presence of TGF-alpha in follicular fluid and the simultaneous absence of EGF suggests that TGF-alpha plays a more pronounced role than EGF in oocyte maturation during late follicular phase.