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Serine protease inhibitor disrupts sperm motility leading to reduced fertility in female mice†.
Biology of Reproduction ( IF 3.1 ) Pub Date : 2020-04-18 , DOI: 10.1093/biolre/ioaa049
Brooke E Barton 1 , Jenna K Rock 1 , Anna M Willie 1 , Emily A Harris 1 , Ryan M Finnerty 1 , Gerardo G Herrera 1 , Prashanth Anamthathmakula 1 , Wipawee Winuthayanon 1
Affiliation  

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.

中文翻译:

丝氨酸蛋白酶抑制剂破坏精子活力,导致雌性小鼠生育能力降低†。

女性生殖道中精子运输过程的抑制可能导致不育。我们以前表明,泛丝氨酸蛋白酶抑制剂 4-(2-氨基乙基) 苯磺酰氟 (AEBSF) 在体内阻止精液液化并导致雌性小鼠输卵管中精子数量急剧减少。在这项研究中,我们使用小鼠模型来测试 AEBSF 作为可逆避孕药、精子活力抑制剂和杀精子剂的功效。此外,本研究还评估了 AEBSF 对体内小鼠阴道组织和体外人宫颈管细胞的毒性。我们发现,与载体对照相比,用 AEBSF 治疗的雌性小鼠每窝出生的幼崽以及体内受精率显着减少。然后我们发现 AEBSF 以剂量依赖性方式降低体外精子活力和受精能力。此外,AEBSF 还表现出杀精子作用。最后,AEBSF 在雌性小鼠中处理 10 分钟或连续 3 天不会改变体内阴道细胞的活力,类似于载体和未处理的对照。然而,AEBSF 降低了体外人宫颈 (ECT) 细胞系的细胞活力,表明小鼠和人类下生殖道中的细胞对 AEBSF 的反应不同。总之,我们的研究表明,AEBSF 可作为原型化合物,通过靶向女性生殖道中的精子运输,进一步开发新型女性非激素避孕药。AEBSF 在雌性小鼠中处理 10 分钟或连续 3 天不会改变体内阴道细胞的活力,类似于载体和未处理的对照。然而,AEBSF 降低了体外人宫颈 (ECT) 细胞系的细胞活力,表明小鼠和人类下生殖道中的细胞对 AEBSF 的反应不同。总之,我们的研究表明,AEBSF 可作为原型化合物,通过靶向女性生殖道中的精子运输,进一步开发新型女性非激素避孕药。AEBSF 在雌性小鼠中处理 10 分钟或连续 3 天不会改变体内阴道细胞的活力,类似于载体和未处理的对照。然而,AEBSF 降低了体外人宫颈 (ECT) 细胞系的细胞活力,表明小鼠和人类下生殖道中的细胞对 AEBSF 的反应不同。总之,我们的研究表明,AEBSF 可作为原型化合物,通过靶向女性生殖道中的精子运输,进一步开发新型女性非激素避孕药。表明小鼠和人类下生殖道中的细胞对 AEBSF 的反应不同。总之,我们的研究表明,AEBSF 可作为原型化合物,通过靶向女性生殖道中的精子运输,进一步开发新型女性非激素避孕药。表明小鼠和人类下生殖道中的细胞对 AEBSF 的反应不同。总之,我们的研究表明,AEBSF 可作为原型化合物,通过靶向女性生殖道中的精子运输,进一步开发新型女性非激素避孕药。
更新日期:2020-04-18
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