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RESEARCH ARTICLE
Contents Vol 35(18)

Pregabalin alters reproductive performance in male mice and causes congenital anomalies in offspring

Viviane de Fátima Mestre https://orcid.org/0000-0001-5675-6577 A B * , Caio Cezar Nantes Martins https://orcid.org/0000-0002-7873-3533 B , Lorrany Victor de Brito https://orcid.org/0000-0003-0504-526X B , Aline Campos Zeffa https://orcid.org/0000-0002-9072-2925 A B , Camila Salvador Sestário https://orcid.org/0000-0002-9730-3061 A B and Maria José Sparça Salles https://orcid.org/0000-0001-5976-9787 B
+ Author Affiliations
- Author Affiliations

A Graduate Program in Health Sciences, State University of Londrina, Londrina, Paraná, Brazil.

B Department of General Biology, Center for Biological Sciences, State University of Londrina, Londrina, Brazil.

* Correspondence to: vivianemestre@yahoo.com.br

Handling Editor: Andrew Pask

Reproduction, Fertility and Development 35(18) 750-759 https://doi.org/10.1071/RD22287
Submitted: 8 December 2022  Accepted: 31 October 2023  Published online: 24 November 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing

Abstract

Context

Pregabalin is an anticonvulsant drug with analgesic activity for the treatment of neuropathic pain.

Aims

To valuate the toxicity of pregabalin in reproductive parameters, spermatogenesis, and teratogenicity in the offspring of mice.

Methods

Twenty male mice were randomly distributed into two groups: PGB group and group C (n = 10 per group). The animals in the PGB group received, via gavage, 200 mg/kg of pregabalin diluted in distilled water daily, for a period of 45 days. Group C received distilled water under the same experimental design.

Key results

In the paternal parameters of the PGB group, there was a significant increase in the size of the testicles, morphological alterations in the spermatozoa, a decrease in the Johnsen score, an increase in the Leydig cells, and a decrease in the serum level of testosterone. In the intrauterine development parameters of females mated with males from the PGB group, a significant decrease in placental weight, weight and length of fetuses, and fetal viability rate was observed. There was a significant increase in the number of resorptions and post-implantation losses. The significant anomalies observed in the offspring were alteration in the size of the kidneys, absent metacarpals and phalanges, alteration in the sternum, and supernumerary thoracic vertebrae.

Conclusion

Results suggest that pregabalin had toxic effects on the reproductive function of male mice and teratogenic potential.

Implications

The findings of this study may provide new hypotheses, taking into account the risk–benefit ratio for male reproduction and offspring health.

Keywords: congenital malformations, infertility, pregabalin, pregnancy, reproductive performance, spermatogenesis, spermiogenesis, teratozoospermia.

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