Inhibition of sperm motility has recently become a promising target for male contraceptive development. AF- 2364, an analogue of Lonidamine （LND）, had a contraceptive effect when orally administered to adult Sprague...Inhibition of sperm motility has recently become a promising target for male contraceptive development. AF- 2364, an analogue of Lonidamine （LND）, had a contraceptive effect when orally administered to adult SpragueDawley rats. LND can also target mitochondria to inhibit oxygen consumption and block energy metabolism in tumour cells. However, there are no reports of the effects of AF-2364 on human sperm function. Herein we describe the action of AF-2364 on human sperm in vitro, as well as the mechanisms involved. AF-2364 specifically blocked human sperm motility in vitro. Further experiments revealed that AF-2364 can target sperm mitochondrial permeability transition （MPT） pores to induce the loss of sperm mitochondrial membrane potential （AqUm） and decrease ATP generation; however, no significant changes in the cytoskeletal network or the human sperm proteome were detected after exposure to AF-2364. Incubation of AF-2364 with other human or mouse cell lines indicated that the spermicidal effect at the lower concentration was specific. In summary, the spermicidal effect olAF-2364 involves direct action on sperm MPT pores, and this compound should be further investigated as a new spermicide candidate.展开更多
基金This study was supported by grants from 973 programs （No. 2006CB504002 and No. 2009CB941703）, National Natural Science Foundation of China （No. 30630030） and Program for Changjiang Scholars and Innovative Research Team in University （PCSIRT）. We thank Professor C. Yan Cheng of the Center for Biomedical Research, Population Council, New York, USA, for his generous gift of AF-2364.
文摘Inhibition of sperm motility has recently become a promising target for male contraceptive development. AF- 2364, an analogue of Lonidamine （LND）, had a contraceptive effect when orally administered to adult SpragueDawley rats. LND can also target mitochondria to inhibit oxygen consumption and block energy metabolism in tumour cells. However, there are no reports of the effects of AF-2364 on human sperm function. Herein we describe the action of AF-2364 on human sperm in vitro, as well as the mechanisms involved. AF-2364 specifically blocked human sperm motility in vitro. Further experiments revealed that AF-2364 can target sperm mitochondrial permeability transition （MPT） pores to induce the loss of sperm mitochondrial membrane potential （AqUm） and decrease ATP generation; however, no significant changes in the cytoskeletal network or the human sperm proteome were detected after exposure to AF-2364. Incubation of AF-2364 with other human or mouse cell lines indicated that the spermicidal effect at the lower concentration was specific. In summary, the spermicidal effect olAF-2364 involves direct action on sperm MPT pores, and this compound should be further investigated as a new spermicide candidate.
