Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate.
Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate.
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DOI：
10.1095/biolreprod.108.072942
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Richardson, Richard T.
中科院分区：
文献类型：
--
作者：
O'Rand, Michael G.;Widgren, Esther E.;Beyler, Stan;Richardson, Richard T.
Eppin（附睾蛋白酶抑制剂;官方符号SPINLW 1）因其在人类精子表面的特异性和位置而成为男性避孕靶点。我们已经研究了不育雄性猴的抗eppin抗体的效果和重组人精液凝固素（SEMG 1）对人精子活力的影响。抗eppin抗体显著降低人类精子的前向运动力，如通过减少总行进距离、减少直线距离和减少速度所测量的。精子的抗eppin处理显著增加了存在于非进行性精子中的cAMP的量;然而，通过添加cAMP-AM可以拯救约25%的抗体处理的精子，这表明抗eppin处理的精子利用cAMP的能力受损。添加重组人精液凝固蛋白对前向运动具有浓度依赖性抑制作用（弯曲度增加和速度降低）。我们测试了以下假设：与eppin结合的抗eppin抗体随后会阻断SEMG 1与eppin结合。来自不育猴的抗eppin抗体抑制eppin与SEMG 1结合。添加针对eppin（S21 C）的优势C-末端表位制备的亲和纯化抗体对前向运动具有抑制作用（增加的弯曲度、降低的速度和直线距离）。我们的研究结果表明，eppin-精液凝固蛋白结合位点是至关重要的精液液化过程中的精液凝固蛋白在体内的去除和启动的前向运动。我们的结论是eppin-精液凝固蛋白结合位点的人精子表面是一个理想的目标，非甾体男性避孕药。
Eppin (epididymal protease inhibitor; official symbol SPINLW1) is of interest as a male contraceptive target because of its specificity and location on the human sperm surface. We have examined the effect of anti-eppin antibodies from infertile male monkeys and the effect of recombinant human semenogelin (SEMG1) on human sperm motility. Anti-eppin antibodies significantly decreased the progressive motility of human spermatozoa as measured by decreased total distance traveled, decreased straight line distance and decreased velocity. Anti-eppin treatment of spermatozoa significantly increased the amount of cAMP present in non-progressive spermatozoa; however, approximately 25% of antibody treated spermatozoa could be rescued by the addition of cAMP-AM, indicating that anti-eppin treated spermatozoa have a compromised ability to utilize cAMP. Addition of recombinant human semenogelin has a concentration dependent inhibitory effect on progressive motility (increased tortuosity and decreased velocity). We tested the hypothesis that anti-eppin antibodies bound to eppin would subsequently block SEMG1 binding to eppin. Anti-eppin antibodies from infertile monkeys inhibited eppin from binding to SEMG1. Addition of affinity purified antibodies made to the dominant C-terminal epitope of eppin (S21C) had an inhibitory effect on progressive motility (increased tortuosity, decreased velocity and straight distance). Our results suggest that the eppin-semenogelin binding site is critical for the removal of semenogelin in vivo during semen liquefaction and the initiation of progressive motility. We conclude that the eppin-semenogelin binding site on the surface of human spermatozoa is an ideal target for a non-steroidal male contraceptive.
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DOI：
10.1073/pnas.0400050101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Esposito, G;Jaiswal, BS;Gossen, JA
通讯作者：
Gossen, JA
影响因子：
3.6
作者：
Luconi, M;Porazzi, I;Baldi, E
通讯作者：
Baldi, E
影响因子：
4.1
作者：
O'Rand, M. G.;Widgren, E. E.;Richardson, R. T.
通讯作者：
Richardson, R. T.
影响因子：
6.1
作者：
ROBERT, M;GAGNON, C
通讯作者：
GAGNON, C
影响因子：
6.1
作者：
Sloter, E.;Schmid, T. E.;Wyrobek, A. J.
通讯作者：
Wyrobek, A. J.