Reversible Contraceptive Potential of FDA Approved Excipient N, N-Dimethylacetamide in Male Rats

Nupur Khera; Chafik Ghayor; Anna K Lindholm; Ekaterina Pavlova; Nina Atanassova; Franz E Weber

doi:10.3389/fphys.2020.601084

Reversible Contraceptive Potential of FDA Approved Excipient N, N-Dimethylacetamide in Male Rats

Front Physiol. 2020 Nov 10:11:601084. doi: 10.3389/fphys.2020.601084. eCollection 2020.

Authors

Nupur Khera^{1

2}, Chafik Ghayor¹, Anna K Lindholm³, Ekaterina Pavlova⁴, Nina Atanassova⁴, Franz E Weber^{1

2

5}

Affiliations

¹ Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zurich, Zurich, Switzerland.
² Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
³ Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
⁴ Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.
⁵ Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.

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.

Keywords: BET inhibitor; bromodomain (BRD); excipient; male contraception; rat; reproduction.