Direct effects of progesterone and antiprogesterone on human sperm hyperactivated motility and acrosome reaction.
OBJECTIVE
To study the direct effects of progesterone (P) and its antagonist RU486 (mifepristone) on sperm hyperactivation (HA) and acrosome reaction.


METHODS
Prospective evaluation of semen samples incubated in capacitation media with P and/or RU486.


METHODS
University-affiliated tertiary care center.


METHODS
Normal healthy volunteers.


METHODS
Semen samples were incubated in media with P or RU486 alone or in combination, and aliquots were taken at 10 minutes, 1, 5, and 24 hours for HA analyses by computer-aided sperm analysis system, and at 0, 5, and 24 hours for assessment of acrosome reaction by fluorescein-labeled Pisum sativum (pea) agglutinin.


METHODS
HA and acrosome reaction.


RESULTS
Sperm HA was significantly increased at 10 minutes by P both at 10(-7) M (9.27 +/- 1.59%; mean +/- SEM) and 10(-6) M (9.39 +/- 1.94%) when compared with untreated spermatozoa (5.62 +/- 1.59%). The stimulatory effect of P on sperm HA was transient because this was not observed after 1, 5, and 24 hours of incubation. The antiprogesterone RU486 (10(-6) M) alone had no effect and did not abolish the stimulatory effect of P on HA. The %HA was further enhanced by the addition of RU486 at 10(-6) M to P at 10(-7) M (12.43 +/- 3.31%) or P at 10(-6) M (13.52 +/- 4.10%); however, this effect was not significantly different from P alone. Coincubation of P or RU486 with spermatozoa during capacitation did not stimulate the acrosome reaction in the concentrations tested.


CONCLUSIONS
Progesterone directly stimulates human sperm HA transiently. Progesterone has no significant effect on acrosome reaction in capacitating spermatozoa. The effects of P are rapid and not counteracted by RU486, suggesting that the mechanism of action of P may not be mediated by specific P nuclear receptors.
Uhler
M L
ML
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Leung
A
A
Chan
S Y
SY
Wang
C
C
D000177:Acrosome / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D011374:Progesterone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011446:Prospective Studies; D013075:Sperm Capacitation / Q000502:physiology; D013081:Sperm Motility / Q000187:drug effects*
D015735:Mifepristone; D011374:Progesterone