Seipin deficiency increases chromocenter fragmentation and disrupts acrosome formation leading to male infertility.
Seipin deficiency increases chromocenter fragmentation and disrupts acrosome formation leading to male infertility.
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DOI：
10.1038/cddis.2015.188
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发表时间：
2015-07-16
影响因子：
9
通讯作者：
Ye X
中科院分区：
文献类型：
--
作者：
El Zowalaty AE;Baumann C;Li R;Chen W;De La Fuente R;Ye X
Berardinelli-Seip先天性脂肪营养不良2型（Bscl 2，seipin）基因参与脂肪形成。Bscl 2 −/−雄性不育，但有正常的交配行为。Bscl 2 −/−尾部附睾精子计数和精子活力均比对照组低约20倍。Bscl 2 −/−生精小管中精原细胞和精母细胞相对正常，但精子细胞和精子减少。时空表达分析Bscl 2 +/+睾丸表现出突出的Bscl 2转录活性在精母细胞与高原达到出生后第28天左右。Seipin蛋白定位在减数分裂后精子细胞中最丰富，表明精母细胞中Bscl 2 mRNA的翻译抑制。与对照组相比，原位末端标记加检测到Bscl 2 −/−睾丸中精子细胞凋亡增加，膜联蛋白V检测到阳性Bscl 2 −/−圆形精子细胞百分比增加。标记蛋白联会复合体蛋白3和1的免疫荧光（SYCP 3和SYCP 1）和H3 K9 me 3（组蛋白H3在赖氨酸9处三甲基化）在Bscl 2 −/−精母细胞中检测到正常的减数分裂染色体配对和同源染色体联会，但显着增加了具有染色中心碎片的圆形精子细胞和晚期精子细胞以及具有染色质空泡的精子的百分比，表明Bscl 2 −/−精子细胞中的染色质凝聚缺陷。Bscl 2 −/−晚期精子细胞在生精上皮内排列紊乱，尽管波形蛋白免疫荧光检测到支持细胞外观正常。花生凝集素染色显示Bscl 2-/-晚期精子细胞顶体存在各种异常，包括顶体缺失、形状不规则和破碎，表明Bscl 2-/-晚期精子细胞顶体形成缺陷，这可能影响晚期精子细胞在生精上皮中的取向。Mitotracker强烈染色对照精子的中段，但仅非常弱地标记Bscl 2 −/−精子的中段，表明线粒体活性缺陷最有可能导致Bscl 2 −/−精子活力降低。这些数据表明seipin在精子染色质完整性，顶体形成和线粒体活性中的新作用。精子细胞凋亡增加、染色中心断裂增加、染色质凝聚缺陷、顶体形成异常和线粒体活性缺陷导致精子产量减少和精子缺陷，导致Bscl 2 −/−男性不育。
The Berardinelli–Seip congenital lipodystrophy type 2 (Bscl2, seipin) gene is involved in adipogenesis. Bscl2−/− males were infertile but had normal mating behavior. Both Bscl2−/− cauda epididymis sperm count and sperm motility were ~20 × less than control. Bscl2−/− seminiferous tubules had relatively normal presence of spermatogonia and spermatocytes but had reduced spermatids and sperm. Spatiotemporal expression analyses in Bscl2+/+ testes demonstrated prominent Bscl2 transcriptional activity in spermatocytes with a plateau reached around postnatal day 28. Seipin protein localization was most abundant in postmeiotic spermatids, suggesting translational repression of Bscl2 mRNA in spermatocytes. In situ end-labeling plus detected increased spermatid apoptosis in Bscl2−/− testis and annexin V detected increased percentage of positive Bscl2−/− round spermatids compared with control. Immunofluorescence of marker proteins synaptonemal complex proteins 3 and 1 (SYCP3 and SYCP1), and H3K9me3 (histone H3 trimethylated at lysine 9) in germ cell spreads detected normal meiotic chromosome pairing and homologous chromosome synapsis in Bscl2−/− spermatocytes, but significantly increased percentages of round spermatids with chromocenter fragmentation and late spermatids and sperm with chromatin vacuoles, indicating defective chromatin condensation in Bscl2−/− spermatids. Bscl2−/− late spermatids were disorganized within the seminiferous epithelium, despite normal appearance of Sertoli cells detected by vimentin immunofluorescence. Peanut agglutinin staining revealed various abnormalities of acrosomes in Bscl2−/− late spermatids, including the absence, irregular-shaped, and fragmented acrosomes, indicating defective acrosome formation in Bscl2−/− late spermatids, which may affect late spermatid orientation in the seminiferous epithelium. Mitotracker strongly stained the midpiece of control sperm but only very weakly labeled the midpiece of Bscl2−/− sperm, indicating defective mitochondrial activity that most likely contributed to reduced Bscl2−/− sperm motility. These data demonstrate novel roles of seipin in spermatid chromatin integrity, acrosome formation, and mitochondrial activity. Increased spermatid apoptosis, increased chromocenter fragmentation, defective chromatin condensation, abnormal acrosome formation, and defective mitochondrial activity contributed to decreased sperm production and defective sperm that resulted in Bscl2−/− male infertility.
影响因子：
3.7
作者：
Wang R;Sperry AO
通讯作者：
Sperry AO