一種能夠讓未成熟的精子細(xì)胞過早逃離睪丸的化合物或許為避孕藥提供了新的線索。
通過關(guān)閉睪丸所獨(dú)有的基因和蛋白質(zhì),那些從事“男性避孕藥”研究的科學(xué)家最近發(fā)現(xiàn)了許多能夠阻礙精子生成的方法,。
如今,,由美國(guó)紐約市人口理事會(huì)生物醫(yī)學(xué)研究中心的C. Yan Cheng率領(lǐng)的一個(gè)研究小組發(fā)現(xiàn)了一種阻礙精子發(fā)生的新途徑:破壞血液—睪丸屏障——這是睪丸與血液循環(huán)之間的一道細(xì)胞防火墻。
當(dāng)Cheng的研究小組向小鼠的睪丸中注入一種特殊的蛋白質(zhì)片段后,,血液—睪丸屏障便被瓦解了,。
這導(dǎo)致未成熟的精子在它們有能力讓卵子受精之前就過早地離開了睪丸,。
更重要的是,這些變化是可逆的,。研究人員在11月13日的《自然—通訊》網(wǎng)絡(luò)版上報(bào)告了他們的研究成果。
任何潛在的男性避孕藥都需要許多年的驗(yàn)證,,并經(jīng)歷許多的測(cè)試,。
例如,Cheng的研究小組并沒有測(cè)試小鼠爸爸在注入了這種蛋白質(zhì)片段后是否會(huì)有更少的后代,。
但Cheng表示,,與其他潛在的避孕藥相比,,這種蛋白質(zhì)的優(yōu)勢(shì)在于它能夠被生物體自然而少量地生成,從而可能具有良好的耐受性,。(生物谷Bioon.com)
doi:10.1038/ncomms2171
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PMID:
A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
Linlin Su, Dolores D. Mruk, Pearl P.Y. Lie, Bruno Silvestrini & C. Yan Cheng
Cellular events that occur across the seminiferous epithelium in the mammalian testis during spermatogenesis are tightly coordinated by biologically active peptides released from laminin chains. Laminin-γ3 domain IV is released at the apical ectoplasmic specialization during spermiation and mediates restructuring of the blood–testis barrier, which facilitates the transit of preleptotene spermatocytes. Here we determine the biologically active domain in laminin-γ3 domain IV, which we designate F5 peptide, and show that the overexpression of this domain, or the use of a synthetic F5 peptide, in Sertoli cells with an established functional blood–testis barrier reversibly perturbs blood–testis barrier integrity in vitro and in the rat testis in vivo. This effect is mediated via changes in protein distribution at the Sertoli and Sertoli–germ–cell cell interface and by phosphorylation of focal adhesion kinase at Tyr407. The consequences are perturbed organization of actin filaments in Sertoli cells, disruption of the blood–testis barrier and spermatid loss. The impairment of spermatogenesis suggests that this laminin peptide fragment may serve as a contraceptive in male rats.