β-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility.
β-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility.
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β-防御素 19/119 介导精子趋化性并与特发性不孕症相关
DOI：
10.1016/j.xcrm.2022.100825
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发表时间：
2022-12-20
影响因子：
14.3
通讯作者：
Fok, Kin Lam
中科院分区：
文献类型：
--
作者：
Li, Xiaofeng;Yuan, Chun;Shi, Jianwu;Kang, Hang;Chen, Yufei;Duan, Yonggang;Jin, Jing;Cheung, Lai Ping;Li, Tin Chiu;Liu, Ying;Cui, Yugui;Ruan, Ye Chun;Jiang, Xiaohua;Cai, Zhiming;Chan, Hsiao Chang;Ji, Ling;Zeng, Xuhui;Liu, Jiaying;Chen, Hao;Fok, Kin Lam
精子趋化性是引导精子向卵子运动所必需的。然而，生理化学引诱物的分子身份及其在不孕症中的作用仍然是难以捉摸的。在这里，我们确定DEFB 19/119（小鼠/人直系同源物）作为生理精子化学引诱物。雌性生殖道上皮细胞和卵丘-卵母细胞复合体分泌DEFB 19/119，其通过CatSper通道促进钙动员并诱导获能精子中的精子趋化性。操纵小鼠体内DEFB 19的水平决定了到达受精部位的精子数量。更重要的是，我们在卵泡液中DEFB 119水平低的特发性不孕妇女中鉴定了DEFB 119基因的外显子突变。DEFB 119水平与卵泡液的趋化能力相关，并与不孕结局呈正相关。本研究揭示了DEFB 19/119在精子趋化性中的关键作用，并展示了其在诊断特发性不育症中的潜在应用。DEFB 119/DEFB 19是人类和小鼠精子趋化性的生理化学引诱物，DEFB 19介导沿着女性生殖道的多阶段趋化性。描述了雌性生殖道中的多级趋化性，其通过生理化学引诱物DEFB 19/119将精子引导至受精位点和卵母细胞。DEFB 119基因突变可能是女性不明原因不孕的原因之一。
Sperm chemotaxis is required for guiding sperm toward the egg. However, the molecular identity of physiological chemoattractant and its involvement in infertility remain elusive. Here, we identify DEFB19/119 (mouse/human orthologs) as a physiological sperm chemoattractant. The epithelia of the female reproductive tract and the cumulus-oocyte complex secrete DEFB19/119 that elicits calcium mobilization via the CatSper channel and induces sperm chemotaxis in capacitated sperm. Manipulating the level of DEFB19 in mice determines the number of sperm arriving at the fertilization site. Importantly, we identify exon mutations in the DEFB119 gene in idiopathic infertile women with low level of DEFB119 in the follicular fluid. The level of DEFB119 correlates with the chemotactic potency of follicular fluid and predicts the infertile outcome with positive correlation. This study reveals the pivotal role of DEFB19/119 in sperm chemotaxis and demonstrates its potential application in the diagnosis of idiopathic infertility. DEFB119/DEFB19 are physiological chemoattractants for sperm chemotaxis in human and mouse DEFB19 mediates multistage chemotaxis along the female reproductive tract DEFB119 gene mutations are associated with idiopathic infertility in women Li et al. describe the multistage chemotaxis in the female reproductive tract that guides the sperm to the fertilization site and the oocyte by the physiological chemoattractant DEFB19/119. Mutations in DEFB119 gene may underlie unexplained infertility in women.
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影响因子：
64.5
作者：
Chung JJ;Shim SH;Everley RA;Gygi SP;Zhuang X;Clapham DE
通讯作者：
Clapham DE
DOI：
10.1126/science.aad6887
发表时间：
2016-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Miller MR;Mannowetz N;Iavarone AT;Safavi R;Gracheva EO;Smith JF;Hill RZ;Bautista DM;Kirichok Y;Lishko PV
通讯作者：
Lishko PV
影响因子：
3.7
作者：
Armon L;Caplan SR;Eisenbach M;Friedrich BM
通讯作者：
Friedrich BM
影响因子：
3.6
作者：
Goodson, Summer G.;Zhang, Zhaojun;O'Brien, Deborah A.
通讯作者：
O'Brien, Deborah A.
影响因子：
11.4
作者：
Brenker, Christoph;Goodwin, Normann;Struenker, Timo
通讯作者：
Struenker, Timo