Follicle-Stimulating Hormone Glycosylation Variants Distinctly Modulate Pre-antral Follicle Growth and Survival.
Follicle-Stimulating Hormone Glycosylation Variants Distinctly Modulate Pre-antral Follicle Growth and Survival.
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DOI：
10.1210/endocr/bqac161
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发表时间：
2022-10-23
期刊：
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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卵泡刺激素(FSH)是卵巢功能的重要内分泌调节因子。FSH以两种大糖基化形式分泌：部分糖基化的FSH(FSH21/18)和完全糖基化的FSH(FSH24)。FSH21/18在结合和激活FSH受体(R)方面比FSH24更有效。FSH21/18/FSH24比值随年龄增长而变化，生殖盛期以FSH21/18为主，围绝经期以FSH24为主。这些FSH糖基化变体如何调节卵巢卵泡功能在很大程度上仍不清楚。本研究的目的是探讨FSH糖基化突变体对腔前卵泡功能的影响。分离3~5周龄C57BL/6小鼠的腔前卵泡，分别处理±10 ng/mLFSH21/18、FSH24、80：20FSH21/18：FSH24(模拟生殖原始期)、50：50FSH21/18：FSH24(围绝经期)或20：80FSH21/18：FSH24(绝经)96h。FSH21/18和80：20FSH21/18：FSH24促进卵泡生长，与对照组相比，与FSH24和20：80FSH21/18：FSH24相比，FSH21/18：FSH24促进卵泡生长。FSH24或20：80FSH21/18：FSH24处理的卵泡存活率降低，卵泡基底膜破裂，卵母细胞排出，Caspase3基因和蛋白表达增加，细胞增殖标志减少。此外，这与调节卵泡功能的关键基因的不同调控有关。关键的FSH信号通路的药物抑制剂提示FSH21/18和FSH24启动了不同的FSHR信号通路激活，这可能决定了它们对卵泡生长和存活的不同影响。这些数据表明，FSH糖基化的性质调节了卵泡细胞环境，以调节卵泡的生长和存活，并可能支持在衰老过程中观察到的卵巢对FSH抵抗力的增加。
Follicle-stimulating hormone (FSH) is a key endocrine regulator of ovarian function. FSH is secreted as 2 macroglycosylation variants: partially glycosylated FSH (FSH21/18) and fully glycosylated FSH (FSH24). FSH21/18 is more potent than FSH24 at binding to and activating the FSH receptor (R). The ratio of FSH21/18:FSH24 has been shown to change with age, with FSH21/18 predominant at reproductive prime, and FSH24 predominant during perimenopause/menopause. How these FSH glycosylation variants modulate ovarian follicle functions remains largely unknown. The aim of this study was to investigate the effect of FSH glycosylation variants of pre-antral follicle function. Pre-antral follicles were isolated from 3- to 5-week-old C57BL/6 mice and treated ±10 ng/mL FSH21/18, FSH24, a ratio of 80:20 FSH21/18:FSH24 (to mimic reproductive prime), 50:50 FSH21/18:FSH24 (perimenopause), or 20:80 FSH21/18:FSH24 (menopause) for up to 96 hours. FSH21/18 and 80:20 FSH21/18:FSH24 increased follicle growth, in comparison with control, contrasting with FSH24 and 20:80 FSH21/18:FSH24. Survival rates were decreased in follicles treated with FSH24 or 20:80 FSH21/18:FSH24, with follicles undergoing basement membrane rupture and oocyte extrusion, increased Caspase3 gene and protein expression, and decreased markers of cell proliferation in FSH24 or 20:80 FSH21/18:FSH24–treated follicles. Moreover, this correlated with differential regulation of key genes modulating follicular functions. Pharmacological inhibitors of key FSH signal pathways suggests FSH21/18 and FSH24 initiate different FSHR signal pathway activation, which may determine their differential effects on follicle growth and survival. These data suggest that the nature of FSH glycosylation modulates the follicular cellular environment to regulate follicle growth and survival and may underpin the increasing ovarian resistance to FSH observed during aging.
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DOI：
10.3791/52458
发表时间：
2015-03-17
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Morgan S;Campbell L;Allison V;Murray A;Spears N
通讯作者：
Spears N
影响因子：
3.8
作者：
Abel, MH;Huhtaniemi, I;Charlton, HM
通讯作者：
Charlton, HM
影响因子：
4.8
作者：
Donaubauer, Elyse M.;Hunzicker-Dunn, Mary E.
通讯作者：
Hunzicker-Dunn, Mary E.
影响因子：
4.1
作者：
Faddy, MJ
通讯作者：
Faddy, MJ
影响因子：
2.9
作者：
Dalpathado, Dilusha S.;Irungu, Janet;Desaire, Heather
通讯作者：
Desaire, Heather