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

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids Pub Date : 2025-05-01 DOI:10.1016/j.steroids.2025.109626

Karina Sequeira , Soledad Henríquez , Paulina Kohen , Ariel Fuentes , Alejandro Tapia-Pizarro , Pablo Céspedes , Ana Godoy , Luigi Devoto

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引用次数: 0

Abstract

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.

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在体外受精周期控制卵巢过度刺激的波塞冬4组妇女的颗粒细胞中，类固醇硫酸酯酶和硫酸类固醇转运蛋白上调

目的脱氢表雄酮硫酸酯（DHEA-S）循环水平降低与卵巢反应不良有关。35岁，处于可控卵巢过度刺激周期的低卵巢储备（POSEIDON组4，PG4）。在卵巢中，脱氢表雄酮- s的摄取是由跨膜有机阴离子转运多肽OATP2B1促进的，而在细胞质中，无活性的前体脱氢表雄酮- s水解成具有生物活性的类固醇脱氢表雄酮是由类固醇硫酸酯酶（STS）催化的。本研究的目的是评估PG4期女性血清和卵泡液中DHEA和DHEA- s以及颗粒细胞中STS和OATP2B1的表达水平，并与年龄匹配的正常卵巢储备和对控制性卵巢过度刺激反应的对照组（对照）进行比较。方法前瞻性研究纳入23例体外受精妇女。我们比较了PG4女性（n = 13）和对照组（n = 8）。在取卵时收集的颗粒细胞中分别采用qPCR和免疫荧光检测STS和OATP2B1转运体的转录水平和细胞分布。根据年龄、循环AMH、窦卵泡计数（AFC）、血清和卵泡液中脱氢表雄酮（DHEA- s）和脱氢表雄酮（DHEA）分析基因表达。结果血清和卵泡液分析显示，与对照组相比，PG4组DHEA- s显著降低，而DHEA浓度无显著差异。PG4组女性的STS和OATP2B1 mRNA表达明显增高(n = 13, p <；0.05)。结论PG4期女性颗粒细胞中STS和OATP2B1的上调可能是一种代偿机制，以克服循环中DHEA- s水平的降低，而DHEA- s可能是卵巢内生成DHEA所必需的底物。

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来源期刊

Steroids 医学-内分泌学与代谢

CiteScore

5.10

自引率

3.70%

发文量

120

审稿时长

73 days

期刊介绍： STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.