title: An in vitro study of the effect of mifepristone and ulipristal acetate on human sperm functions.
abstract: Ulipristal acetate (UPA) and mifepristone are currently well-established agents for emergency contraception. Both drugs are selective progestogen receptor modulators which have been shown to have better efficacy than the widely used levonorgestrel in prevention of pregnancy. However, there is only limited information on the action of UPA on sperm function. The present study compared the in vitro biological effects of mifepristone and UPA on human sperm functions. Spermatozoa from semen samples with normal semen parameters were isolated. Capacitated spermatozoa were pre-incubated with 0.04, 0.4, 4 and 40 μM mifepristone or UPA for 1 h. Sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, zona pellucida (ZP) binding capability and intracellular calcium concentration ([Ca(2+)]i) were determined. The effects of mifepristone and UPA on progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i were also studied. Our results showed that mifepristone and UPA dose-dependently suppressed progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i at concentrations ≥0.4 μM in human spermatozoa. Both compounds did not affect sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, ZP binding capability and [Ca(2+)]i. This study demonstrated that UPA and mifepristone modulate human sperm functions by acting as progesterone antagonists. The results enable us to gain a better understanding of the mechanisms by which mifepristone and UPA work for emergency contraception, and provide a scientific basis for their clinical application.
authors.affiliation: Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: J K Y
authors.initials: JK
authors.lastname: Ko
authors.forename: V W
authors.initials: VW
authors.lastname: Huang
authors.forename: R H W
authors.initials: RH
authors.lastname: Li
authors.forename: W S B
authors.initials: WS
authors.lastname: Yeung
authors.forename: P C
authors.initials: PC
authors.lastname: Ho
authors.forename: P C N
authors.initials: PC
authors.lastname: Chiu
mesh_terms: D020101:Acrosome Reaction; D002118:Calcium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009649:Norpregnadienes / Q000494:pharmacology*; D013075:Sperm Capacitation; D013081:Sperm Motility; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D009649:Norpregnadienes; D015735:Mifepristone; D002118:Calcium; C555622:ulipristal acetate
keywords: fertilization; mifepristone; progesterone; spermatozoa; ulipristal acetate