Direct effects of progesterone and antiprogesterone on human sperm hyperactivated motility and acrosome reaction.

Abstract:

OBJECTIVE:To study the direct effects of progesterone (P) and its antagonist RU486 (mifepristone) on sperm hyperactivation (HA) and acrosome reaction. DESIGN:Prospective evaluation of semen samples incubated in capacitation media with P and/or RU486. SETTING:University-affiliated tertiary care center. PATIENTS:Normal healthy volunteers. INTERVENTIONS: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. MAIN OUTCOME MEASURES: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. CONCLUSION: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. :Reproductive endocrinologists at the University of California, Los Angeles Medical Center, obtained semen samples from healthy volunteers to examine the direct effects of progesterone and the antiprogesterone RU-486 on sperm hyperactivation and acrosome reaction, which they hoped would elucidate progesterone's mechanism of action. They used progesterone concentrations which match those of the female reproductive tract. Progesterone induced a considerable increase in sperm hyperactivation at 10 millionths M and 1 millionth M after 10 minutes (9.27% and 9.39% vs. 5.62% for untreated spermatozoa; p .05). The ability of progesterone to increase sperm hyperactivation was only temporary, however. In fact, progesterone had no effect at 1, 5, and 24 hours. RU-486 alone did not affect sperm hyperactivation. Addition of RU-486 at 1 millionth M to progesterone further did strengthen the stimulatory effect, however, but it was not significant (13.52% vs. 9.39%). When progesterone or RU-486 were coincubated with spermatozoa during the process by which they become able to fertilize the ovum after they are at the ampullar portion of the uterine tube, neither chemical stimulated the acrosome reaction, regardless of the concentration. These results indicated that progesterone can only directly stimulate sperm hyperactivation temporarily and rapidly (within about 10 minutes) and does not influence acrosome reaction during capacitation. They also demonstrated that RU-486 cannot counteract progesterone. Thus, specific progesterone receptors do not mediate progesterone's mechanism of action.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

Uhler ML,Leung A,Chan SY,Wang C

keywords:

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

1191-8

issue

6

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(16)55568-X

journal_volume

58

pub_type

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