Steroid sulfatase and the transporter of sulfated steroids are upregulated in granulose cells from women of POSEIDON group 4 in controlled ovarian hyperstimulation for in vitro fertilization cycles.

PURPOSE: The reduced circulating levels of dehydroepiandrosterone sulphate (DHEA-S) are associated with women with poor ovarian response, > 35 years old and low ovarian reserve (POSEIDON group 4, PG4) in cycles of controlled ovarian hyperstimulation. In the ovary, the uptake of DHEA-S is facilitated by the transmembrane organic anion-transporting polypeptide, OATP2B1, whereas in the cytoplasm, the hydrolysis of the inactive precursor DHEA-S into the biologically active steroid DHEA is catalyzed by the steroid sulfatase enzyme (STS). The objective of the present study was to evaluate DHEA and DHEA-S in serum and follicular fluid as well as the expression levels for STS and OATP2B1 in granulosa cells from women in PG4 compared to a control group (control) of age matched women with normal ovarian reserve and response to controlled ovarian hyperstimulation.

METHODS

Prospective study which included 23 women who underwent in vitro fertilization. We compared women in PG4 (n = 13) with a control (n = 8). Transcript levels and the cellular distribution of STS and OATP2B1 transporter were determined by qPCR and immunofluorescence respectively in granulosa cells collected at the time of oocyte pick-up. Gene expression was analyzed according to age, circulating AMH, antral follicle count (AFC) along with DHEA-S and DHEA in serum and follicular fluid.

RESULTS

Serum and follicular fluid analysis showed that DHEA-S was significantly decreased in PG4 compared to control, whereas no differences in DHEA concentrations were observed. Women in PG4 had significantly higher expression of STS and OATP2B1 mRNA (n = 13, p < 0.05) compared with those of the control.

CONCLUSION

Our results suggest that up-regulation of STS and OATP2B1 in granulosa cells from women in PG4 could be a compensatory mechanism to overcome the decreased circulating levels of DHEA-S possibly required as substrate for intraovarian production of DHEA.