Human follicular fluid elicits select dose- and age-dependent effects on mouse oocytes and cumulus-oocyte complexes in a heterologous in vitro maturation assay.
Human follicular fluid elicits select dose- and age-dependent effects on mouse oocytes and cumulus-oocyte complexes in a heterologous in vitro maturation assay.
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在异源体外成熟测定中，人卵泡液对小鼠卵母细胞和卵丘-卵母细胞复合物产生选择性剂量和年龄依赖性影响。
DOI：
10.1093/molehr/gaad039
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发表时间：
2023
影响因子：
4
通讯作者：
Duncan,FrancescaE
中科院分区：
文献类型：
--
作者：
Dipali,ShwetaS;Suebthawinkul,Chanakarn;Burdette,JoannaE;Pavone,MaryEllen;Duncan,FrancescaE
卵泡液（FF）是窦卵泡内卵母细胞的主要微环境。尽管一些研究已经定义了人类 FF 在正常生理学中的组成，并确定了它在疾病状态下如何改变，但人类 FF 对卵母细胞的直接影响尚不清楚。获得合适数量的人类卵母细胞用于研究非常困难，这使得解决这一问题具有挑战性。因此，我们使用异源模型，在人类 FF 中培养小鼠卵母细胞。为了确定 FF 对配子质量是否具有剂量依赖性影响，我们对来自中期生育年龄（32-36 岁）参与者的 10%、50% 或 100% FF 的幼龄小鼠（6-12 周）的裸露卵母细胞进行了体外成熟。 FF 以剂量依赖性方式影响减数分裂能力，浓度 >10% 会抑制减数分裂进展并导致纺锤体和染色体排列缺陷。我们之前证明，人类 FF 随着年龄的增长而获得纤维炎症细胞因子特征。因此，为了确定暴露于衰老的 FF 微环境是否会导致配子质量的年龄依赖性下降，我们使年轻（28-30 岁）和老年（40-42 岁）参与者的 FF 中的裸露卵母细胞和卵丘-卵母细胞复合物（COC）成熟。 FF 以年龄依赖性方式减少了年轻和年老（9-12 个月）小鼠的 COC 减数分裂进程，但不减少卵母细胞的减数分裂进程。此外，FF 对裸卵母细胞中的线粒体聚集和 COC 中的卵丘层扩张动力学具有适度的年龄依赖性影响，这可能会影响受精或早期胚胎发育。总体而言，这些发现表明，急性人类 FF 暴露可以以剂量和年龄依赖性方式影响小鼠卵母细胞质量的选择标记。
Follicular fluid (FF) is a primary microenvironment of the oocyte within an antral follicle. Although several studies have defined the composition of human FF in normal physiology and determined how it is altered in disease states, the direct impacts of human FF on the oocyte are not well understood. The difficulty of obtaining suitable numbers of human oocytes for research makes addressing such a question challenging. Therefore, we used a heterologous model in which we cultured mouse oocytes in human FF. To determine whether FF has dose-dependent effects on gamete quality, we performedin vitromaturation of denuded oocytes from reproductively young mice (6–12 weeks) in 10%, 50%, or 100% FF from participants of mid-reproductive age (32–36 years). FF impacted meiotic competence in a dose-dependent manner, with concentrations >10% inhibiting meiotic progression and resulting in spindle and chromosome alignment defects. We previously demonstrated that human FF acquires a fibro-inflammatory cytokine signature with age. Thus, to determine whether exposure to an aging FF microenvironment contributes to the age-dependent decrease in gamete quality, we matured denuded oocytes and cumulus–oocyte complexes (COCs) in FF from reproductively young (28–30 years) and old (40–42 years) participants. FF decreased meiotic progression of COCs, but not oocytes, from reproductively young and old (9–12 months) mice in an age-dependent manner. Moreover, FF had modest age-dependent impacts on mitochondrial aggregation in denuded oocytes and cumulus layer expansion dynamics in COCs, which may influence fertilization or early embryo development. Overall, these findings demonstrate that acute human FF exposure can impact select markers of mouse oocyte quality in both dose- and age-dependent manners.