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.
02 - 04 Sep 2014
World Congress of Reproductive Biology