Serine protease inhibitor disrupts sperm motility leading to reduced fertility in female mice

被引:10
作者
Barton, Brooke E. [1 ]
Rock, Jenna K. [1 ]
Willie, Anna M. [1 ]
Harris, Emily A. [1 ]
Finnerty, Ryan M. [1 ]
Herrera, Gerardo G. [1 ]
Anamthathmakula, Prashanth [1 ]
Winuthayanon, Wipawee [1 ]
机构
[1] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Ctr Reprod Biol, Pullman, WA 99164 USA
基金
美国国家卫生研究院;
关键词
protease inhibitor; contraceptive; spermicide; sperm motility; fertility; semen liquefaction; vaginal toxicity; VAGINAL MICROBICIDE; IN-VITRO; NONOXYNOL-9; TRANSMISSION; SEMENOGELIN; VIVO; GEL;
D O I
10.1093/biolre/ioaa049
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Inhibition of the sperm transport process in the female reproductive tract could lead to infertility. We previously showed that a pan-serine protease inhibitor, 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), blocked semen liquefaction in vivo and resulted in a drastic decrease in the number of sperm in the oviduct of female mice. In this study, we used a mouse model to test the efficacy of AEBSF as a reversible contraceptive, a sperm motility inhibitor, and a spermicide. Additionally, this study evaluated the toxicity of AEBSF on mouse vaginal tissues in vivo and human endocervical cells in vitro. We found that female mice treated with AEBSF had significantly less pups born per litter as well as fertilization rates in vivo compared to the vehicle control. We then showed that AEBSF reduced sperm motility and fertilization capability in vitro in a dose-dependent manner. Furthermore, AEBSF also exhibited spermicidal effects. Lastly, AEBSF treatment in female mice for 10 min or 3 consecutive days did not alter vaginal cell viability in vivo, similar to that of the vehicle and non-treated controls. However, AEBSF decreased cell viability of human ectocervical (ECT) cell line in vitro, suggesting that cells in the lower reproductive tract in mice and humans responded differently to AEBSF. In summary, our study showed that AEBSF can be used as a prototype compound for the further development of novel non-hormonal contraceptives for women by targeting sperm transport in the female reproductive tract.
引用
收藏
页码:400 / 410
页数:11
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