Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI

Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI
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DOI:
10.1093/humrep/dei169
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发表时间:
2005-11-01
期刊:
影响因子:
6.1
通讯作者:
Meistrich, ML
Meistrich, ML
中科院分区:
医学1区
文献类型:
--
作者:
Suganuma, R;Yanagimachi, R;Meistrich, ML

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背景技术背景:最近的研究表明,分别用不育小鼠或男性的附睾尾部或射出精子进行ICSI,在受精和正常胚胎发育方面不如用睾丸精子进行ICSI有效。这些研究表明,精子从睾丸中释放后核质量下降,但这种生育能力丧失的部位尚未定位。方法:我们对来自不育Tnp 1-/-Tnp 2 +/-突变小鼠的睾丸、附睾头和附睾尾精子进行了ICSI,这些小鼠具有最低水平的过渡核蛋白,并且通过自然交配不育。研究结果:将Tnp 1-/-Tnp 2 +/-雄性小鼠睾丸或附睾头的活动精子头部注射到去核小鼠卵母细胞中时,精子染色体与野生型小鼠的精子染色体没有差异,但突变雄性小鼠附睾尾的精子染色体异常增加。将来自Tnp 1-/-Tnp 2 +/-雄性小鼠的睾丸或附睾头精子注射到完整的卵母细胞中,导致正常的胚胎和胎儿发育,活产率与野生型相当,但来自Tnp 1-/-Tnp 2-/-小鼠的尾部精子产生的着床率和活产率低于野生型小鼠。结论:这些结果表明,在精子染色质异常的小鼠中,ICSI精子的生育力下降发生在附睾头之后。在某些情况下,使用附睾头精子进行ICSI的优势可能被认为是人类辅助生殖的一种方法。
BACKGROUND: Recent studies showed that ICSI with cauda epididymal or ejaculated sperm of infertile mice or men, respectively, was less effective in fertilization and normal embryo development than ICSI using sperm from the testes. These studies suggested that sperm nuclear quality declined after release from the testis, but the site where this loss of fertility occurs has not been localized. METHODS: We performed ICSI with testicular, caput, and cauda epididymal sperm from infertile Tnp1-/-Tnp2+/- mutant mice, which have a minimal level of transition nuclear proteins and are sterile by natural mating. RESULTS: When the heads of motile sperm from the testis or caput epididymis of Tnp1-/-Tnp2+/- males were injected into enucleated mouse oocytes, sperm chromosomes showed no difference from those of wild-type mice, but the chromosomes from sperm taken from the cauda epididymis of mutant males showed increased abnormalities. Injection of testicular or caput epididymal sperm from Tnp1-/-Tnp2+/- males into intact oocytes resulted in normal embryonic and fetal development and yields of liveborn equivalent to wild-type, but cauda sperm from Tnp1-/-Tnp2-/- mice produced lower implantation rates and yields of liveborn than did those from wild-type mice. CONCLUSIONS: These results demonstrate that in mice with sperm chromatin abnormalities, the decline in fertility of sperm with ICSI occurs after the caput epididymis. The advantage of using caput epididymal sperm for ICSI in certain situations may be considered as an approach to be tested in human assisted reproduction.