AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility.
AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility.
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DOI：
10.1038/s41420-021-00738-z
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发表时间：
2021-11-11
影响因子：
7
通讯作者：
Gui Y
中科院分区：
文献类型：
--
作者：
Ma Q;Cao C;Zhuang C;Luo X;Li X;Wan H;Ye J;Chen F;Cui L;Zhang Y;Wen Y;Yuan S;Gui Y
精子发生是一个复杂的过程，依赖于无数睾丸丰富的基因调控的复杂协调。协调这一过程的调控途径还没有得到很好的理解，我们在这里证明，AXDND 1，作为一种新的睾丸富集基因是精子发生和男性生育力所必需的。AXDND 1仅在人和小鼠的圆形和伸长精子细胞中表达。我们通过选择性外显子测序确定了非梗阻性无精子症（NOA）患者特有的AXDND 1的两个潜在有害突变。重要的是，Axdnd1基因敲除的雄性不育，睾丸大小减少，这是由生殖细胞凋亡增加和脱落引起的，表现出与少弱畸形精子症一致的表型。Axdnd1突变的晚期精子细胞表现为头部变形，轴丝中的外部双重微管缺乏，以及相应的附属结构，包括外部致密纤维（ODF）和线粒体鞘的丢失。这些表型可能是由于扰乱行为的manchette，一个动态的结构，AXDND 1本地化。我们的研究结果表明，AXDND 1可能是一个新的睾丸富集基因，它可能通过调节精子的柄动态、精子细胞头部的形成和精子鞭毛的组装而对精子发生和男性生育力至关重要。
Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.
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影响因子：
4.5
作者：
Liu Y;DeBoer K;de Kretser DM;O'Donnell L;O'Connor AE;Merriner DJ;Okuda H;Whittle B;Jans DA;Efthymiadis A;McLachlan RI;Ormandy CJ;Goodnow CC;Jamsai D;O'Bryan MK
通讯作者：
O'Bryan MK
影响因子：
2.5
作者：
Kierszenbaum, Abraham L.;Rivkin, Eugene;Tres, Laura L.;Yoder, Bradley K.;Haycraft, Courtney J.;Bornens, Michel;Rios, Rosa M.
通讯作者：
Rios, Rosa M.
影响因子：
4.8
作者：
Gingras, D;White, D;Gagnon, C
通讯作者：
Gagnon, C
影响因子：
4.8
作者：
Pleuger, Christiane;Lehti, Mari S.;O'Bryan, Moira K.
通讯作者：
O'Bryan, Moira K.
DOI：
10.1006/bbrc.2001.5776
发表时间：
2001-10-26
影响因子：
3.1
作者：
Yanagisawa, H;Kamiya, R
通讯作者：
Kamiya, R