Expression of Anion Exchanger 1 (AE1) and Its Potential Involvement in Human Granulosa Cell Physiology: An In Vitro Pilot Study

The anion exchanger 1 (AE1), traditionally known for its role in erythrocyte anion transport and acid-base homeostasis, has recently been identified in non-erythroid tissues, suggesting broader physiological functions. In the present study, we investigated for the first time the expression and potential role of AE1 in human ovarian granulosa cells (GCs) obtained from women with endometriosis (ENDO-GCs) or male factor infertility controls (MF-GCs). Cells were cultured in the presence of follicular fluid derived from control (FF-MF) or endometriosis patients (FF-ENDO), and DIDS-sensitive anion exchange activity was pharmacologically inhibited using 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). AE1 expression was evaluated at both protein and transcript levels together with markers of proliferation, inflammation, and steroidogenesis. The results demonstrate that AE1 is constitutively expressed in GCs and may contribute to granulosa cell homeostasis. Inhibition of DIDS-sensitive anion exchange activity inhibited cell proliferation, shifted cell morphology toward a fibroblast-like phenotype, and reduced estradiol and progesterone secretion and inflammatory (IL-6) gene transcription. Notably, MF-GCs cultured in FF-MF exhibited compensatory upregulation of AE1, whereas ENDO-GCs and cells exposed to FF-ENDO showed impaired adaptive responses and generalized transcriptional suppression. These findings provide preliminary evidence supporting a role for DIDS-sensitive anion exchange activity in granulosa cell physiology and warrant further studies to clarify the specific contribution of AE1 to follicular dysfunction associated with endometriosis. However, the specific mechanistic contribution of AE1 could not be established and will require further functional and genetic investigations.