Abstract
Development of an effective male contraceptive agent remains a challenge. The present study evaluates the potential of N, N-Dimethylacetamide (DMA), a FDA approved excipient as a male contraceptive agent. Male Sprague Dawley rats injected with DMA for a period of 8 weeks (one injection per week) showed a significant alteration of reproductive parameters. Furthermore, DMA treated animals showed complete infertility in a dose dependent manner, as no pups were born despite proper mating between females and DMA treated males. However, stopping the DMA treatment for a period of 8 weeks (after the initial treatment) restored the reproductive parameters to normal. Moreover, the fertility was resumed to normal as pups were born in the groups where DMA treatment was halted after initial DMA treatment. All these changes had no effect on the level of reproductive hormones FSH, LH and testosterone. Taken together, our results indicate that DMA acts in a reversible and non-hormonal manner to achieve contraception in rats. Therefore, repurposing the use of DMA could lead in a short time to an inexpensive and safer male contraceptive option.
Highlights
The rate of unwanted pregnancies is globally increasing
We examined the effects of DMA treatment on spermatogenesis and infertility in vivo with emphasis on a possible recovery once the treatment is halted
Since the process of spermatogenesis is conserved over species, results from our rat model could be indicative for a possible use of DMA as a non-hormonal, post meiotically acting and reversible male contraceptive in humans
Summary
The rate of unwanted pregnancies is globally increasing. About 40% of all pregnancies were unintended in 2012 (Sedgh et al, 2014). Certain fraction of women who take the female contraceptive pills have to quit it due to development of high risk of venous thromboembolism, breast cancer and other side effects (McDaid et al, 2017) Another major and often neglected reason leading to unintended pregnancies is the lack of a reliable male contraceptive method (Plana, 2017), leaving couples with limited contraceptive options. The sensitivity of the spermatogenesis process to hormonal regulation was long believed to be a promising route for the development of a male contraceptive (Wang and Swerdloff, 2010) To this end, Testosterone and its analogs have been injected to signal the hypothalamus to stop producing GnRH and inhibiting intra testicular testosterone release. Since the process of spermatogenesis is conserved over species, results from our rat model could be indicative for a possible use of DMA as a non-hormonal, post meiotically acting and reversible male contraceptive in humans
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