Effects of E2/ERβ on follicular granulosa cells and on AMH/Smad signalling in endometriosis

Patients with endometriosis have greater risk of infertility, which is associated with compromised ovarian function. Dysfunction in follicular granulosa cells and hyperactivation of oestrogen receptor beta (ERβ) are evident in endometriosis. It is also known that anti-Müllerian hormone (AMH)/Smad signalling pathway regulates ovarian activity. In this study, we aimed to explore effects of oestradiol (E2)/ERβ on follicular granulosa cells and on AMH/Smad signalling in endometriosis. The human ovarian granulosa cells were obtained from patients with tubal factor infertility and ovarian endometriosis, respectively, who underwent IVF/ICSI-ET using GnRH antagonist protocol in our hospital. A human ovarian granulosa tumour cell line (KGN) was cultured and subject to treatments with oestradiol and/or PHTPP (a selective ERβ antagonist). Cell viability, apoptosis, migration, and invasion were assessed. The mRNA and protein expressions were also investigated. It was found that AMH/Smad signalling pathway was suppressed in human ovarian granulosa cells in patients with ovarian endometriosis. Then, in KGN cells, E2 treatment (10−10  mol/L for 72 h) did not alter cell viability or apoptosis, but E2 decreased migration and invasion via ERβ. Further, E2 inhibited AMH/Smad signalling pathway via ERβ in KGN cells. Conversely, selective inhibition of ERβ could reverse these effects. In conclusion, activation of E2/ERβ compromised the function of follicular granulosa cells in endometriosis, which may be mediated by AMH/Smad signalling pathway.