Structural features of sterols required to inhibit human sperm capacitation.
Structural features of sterols required to inhibit human sperm capacitation.
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抑制人类精子获能所需的甾醇的结构特征。
DOI：
10.1095/biolreprod.102.008607
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Cross,NicholasL
中科院分区：
文献类型：
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作者：
Nimmo,MatthewR;Cross,NicholasL
哺乳动物射出的精子必须经过最后的成熟（获能）才能与顶体反应并使卵子受精。胆固醇的损失是人类精子获能的重要步骤。在实验中，保持高水平的胆固醇会抑制获能，但其机制尚不清楚。本研究调查了胆固醇的抑制活性所需的结构特征。人类精子也含有大量的链甾醇，这是失去精子在获能。防止链甾醇的损失抑制获能（通过顶体反应性评估），其有效性约等于胆固醇的抑制活性。将其他结构类似物添加到孵育培养基中以替代精子胆固醇和链甾醇。大多数抑制获能，包括那些缺乏胆固醇的3β-OH基团（胆固醇甲基醚和表胆固醇）和那些修饰的C17基团（麦角固醇和薯蓣皂苷元）。两种类固醇不能很好地抑制获能。具有非平面类固醇核的粪甾烷醇具有低抑制活性，这可以通过升高的内源性胆固醇浓度来解释。表前列醇具有非平面环状结构和3α-OH基团，促进而不是抑制获能。类似物的抑制活性与它们促进卵磷脂的顺序的能力相关，通过荧光各向异性测量。总之，甾醇抑制活性需要平面环结构，但不需要C17上的3β-OH基团和饱和胆固醇样脂肪族尾部。本研究结果支持精子甾醇通过增加磷脂的顺序来阻断获能的假设。
Ejaculated mammalian sperm must undergo a final maturation (capacitation) before they can acrosome-react and fertilize eggs. Loss of cholesterol is an essential step in the capacitation of human sperm. Experimentally maintaining a high level of cholesterol inhibits capacitation, but the mechanism is unknown. The present study investigated the structural features that are required for cholesterol's inhibitory activity. Human sperm also contain much desmosterol, which is lost from sperm during capacitation. Preventing the loss of desmosterol inhibited capacitation (as assessed by acrosomal responsiveness), with an effectiveness approximately equal to cholesterol's inhibitory activity. Other structural analogs were added to the incubation medium to replace sperm cholesterol and desmosterol. Most inhibited capacitation, including those that lacked cholesterol's 3β-OH group (cholesteryl methyl ether and epicholesterol) and those with modified C17 groups (ergosterol and diosgenin). Two steroids did not inhibit capacitation well. Coprostanol, which has a nonplanar steroid nucleus, had low inhibitory activity that could be explained by an elevated endogenous cholesterol concentration. Epicoprostanol, which has a nonplanar ring structure and a 3α-OH group, promoted rather than inhibited capacitation. The inhibitory activity of the analogs was correlated with their ability to promote order of egg phosphatidylcholine as measured by fluorescence anisotropy. In summary, a planar ring structure is required for sterol inhibitory activity, but a 3β-OH group and a saturated cholesterol-like aliphatic tail on C17 are not required. The present results support the hypothesis that sperm sterols block capacitation by increasing order of phospholipids.