FSH和GDF-9在3D水凝胶培养中调节人窦前卵泡的细胞外基质重塑
FSH and GDF-9 modulate extracellular matrix remodeling in human preantral follicles in a 3D hydrogel culture.
FSH and GDF-9 modulate extracellular matrix remodeling in human preantral follicles in a 3D hydrogel culture.
背景:人类腔前卵泡的发育需要卵母细胞与颗粒细胞之间精细调控的信号传导,并依赖于结构化的细胞外基质(ECM)支持。本研究探讨了在三维细胞培养体系中,卵泡刺激素(FSH)与生长分化因子9(GDF-9)单独或联合使用对卵泡生长及ECM组织的影响。结果:所有培养条件在第1天和第7天均维持了较高的卵泡存活率,组间无显著差异;第7天各条件下的存活率约为69%~76%。第1天时,各组卵泡直径相当。至第7天,未添加FSH或GDF-9培养的卵泡平均直径(171.98 ± 61.05 μm)显著大于同时添加两种补充因子的组(130.22 ± 56.75 μm;p < 0.05);单因子补充组的直径介于两者之间,且与未补充组无显著差异。免疫荧光显示,仅添加FSH组和仅添加GDF-9组的卵泡周边及整个卵泡的层粘连蛋白表达显著高于未补充组和联合补充组。相比之下,IV型胶原呈现出不同的模式:仅添加GDF-9组的IV型胶原总量最低,而联合补充组在周边和总量上的IV型胶原荧光强度均高于仅添加GDF-9组,凸显了同步增殖与组织化信号的重要性。结论:这些发现强调了不仅通过生长情况、还应通过ECM完整性来评估卵泡质量的关键必要性。同时也进一步印证了富含生理性调节因子的无血清培养体系在支持卵母细胞-体细胞协调以及维持卵泡结构方面的转化价值,可应用于生殖工程和生育力保存领域。
BACKGROUND: Human preantral follicle development requires finely tuned signaling between oocytes and granulosa cells, supported by a structured extracellular matrix (ECM). This study investigates how follicle-stimulating hormone (FSH) and growth differentiation factor 9 (GDF-9), alone or combined, influence follicular growth and ECM organization in a 3D cell culture system. RESULTS: All culture conditions maintained high follicle viability on Days 1 and 7 with no significant intergroup differences; Day-7 viability ranged from ~ 69–76% across conditions. On Day 1, follicle diameters were comparable among groups. By Day 7, follicles cultured without added FSH or GDF-9 reached a significantly larger mean diameter (171.98 ± 61.05 μm) than those cultured with both supplements (130.22 ± 56.75 μm; p < 0.05); diameters in single-supplement groups were intermediate and not significantly different from the unsupplemented group. Immunofluorescence revealed that laminin expression at the follicle peripheral and across the whole follicle was significantly higher in the FSH-only and GDF-9-only groups than in the unsupplemented and combined-supplement groups. In contrast, collagen IV exhibited a distinct pattern: total collagen IV was lowest in the GDF-9-only group, whereas combined-supplemented group resulted in the higher collagen IV fluorescent intensity in both peripheral and total compared to GDF-9-only group, highlighting the importance of synchronized proliferative and organizational cues. CONCLUSION: These findings underscore the critical need to evaluate follicle quality not only by growth but also by ECM integrity. They also reinforce the translational value of serum-free systems enriched with physiological regulators to support oocyte-somatic coordination and preserve follicular architecture for reproductive engineering and fertility preservation applications.
Arezoo Dadashzadeh, Saeid Moghassemi, Christiani A Amorim. FSH and GDF-9 modulate extracellular matrix remodeling in human preantral follicles in a 3D hydrogel culture.. Journal of ovarian research. 2026; doi:10.1186/s13048-026-02080-3.
Arezoo Dadashzadeh, Saeid Moghassemi, Christiani A Amorim (2026). FSH and GDF-9 modulate extracellular matrix remodeling in human preantral follicles in a 3D hydrogel culture.. Journal of ovarian research. https://doi.org/10.1186/s13048-026-02080-3
Arezoo Dadashzadeh, Saeid Moghassemi, Christiani A Amorim. FSH and GDF-9 modulate extracellular matrix remodeling in human preantral follicles in a 3D hydrogel culture.[J]. Journal of ovarian research, 2026 doi:10.1186/s13048-026-02080-3.
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