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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P194 | DOI: 10.1530/repabs.1.P194

High-throughput screening revealed a clinically relevant drug to induce sperm motility

Clair Cochrane, Halil Ruso, Anthony Hope, Rosemary G Clarke, Christopher Barratt & Sarah Martins da Silva

University of Dundee, Dundee, UK.

Introduction: Sperm dysfunction is the commonest cause of infertility, yet there is currently no drug a man can take, or be added to his sperm in-vitro, to improve fertility. The rationale of drug discovery research is to find a drug which increases sperm motility and success of ART. Despite limitations in understanding of sperm physiology, it is acknowledged calcium is central to motility and function. Validated high-throughput screening of compounds from University of Dundee Drug Discovery Unit has identified Trequinsin, a potent phosphodiesterase III inhibitor, to induce significant intracellular calcium ([Ca2]i) in human spermatozoa.

Experimental design: Semen from healthy volunteer donors and patients attending Ninewells Assisted Conception Unit (ethical approval 08/S1402/6) was prepared by percoll gradient. Effects of Trequinsin were evaluated in-vitro using CASA. Kremer testing was used to assess functional motility response.

Flow cytometry (FACS) determined the proportion of cells that responded to Trequinsin and evaluated acrosome reaction.

Results: Trequinsin significantly increased total and progressive motility in 40 and 80% sperm fractions from healthy donors under capacitating and non-capacitating conditions (P<0.05). Motility was significantly increased in sperm from a patient affected by failed fertilisation following ICSI.

FACS demonstrated Trequinsin induced an increase in [Ca2]i in a higher proportion of 80% fraction cells (78%) compared to 40% (35%). Acrosome reaction was not significantly increased.

Discussion: Increase in [Ca2]i induced by Trequinsin causes an increase in motility parameters of spermatozoa, including patient samples, without significantly affecting acrosome reaction. Increasing data may provide evidence to justify its use in a clinical setting.

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