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

IF 1.8 4区 生物学 Q3 DEVELOPMENTAL BIOLOGY Reproduction, fertility, and development Pub Date : 2023-11-01 DOI:10.1071/RD22287
Viviane de Fátima Mestre, Caio Cezar Nantes Martins, Lorrany Victor de Brito, Aline Campos Zeffa, Camila Salvador Sestário, Maria José Sparça Salles
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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, 200mg/kg of pregabalin diluted in distilled water daily, for a period of 45days. 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.

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普瑞巴林会改变雄性小鼠的生殖能力,并导致后代的先天性异常。
背景:普瑞巴林是一种具有镇痛活性的抗惊厥药物,用于神经性疼痛的治疗。目的:评价普瑞巴林对小鼠后代生殖参数、精子发生和致畸性的毒性。方法:雄性小鼠20只,随机分为PGB组和C组,每组10只。PGB组每天灌胃用蒸馏水稀释普瑞巴林200mg/kg,连续45天。C组采用蒸馏水,实验设计相同。关键结果:在PGB组的父系参数中,睾丸大小明显增加,精子形态改变,Johnsen评分下降,间质细胞增加,血清睾酮水平下降。雌性与PGB雄性交配后的宫内发育参数中,胎盘重量、胎重、胎长及胎儿存活率均显著降低。再吸收和种植后损失的数量显著增加。在后代中观察到的显著异常是肾脏大小的改变,掌骨和指骨的缺失,胸骨的改变和胸椎的多余。结论:普瑞巴林对雄性小鼠生殖功能有毒性作用,具有致畸潜能。意义:考虑到男性生殖和后代健康的风险收益比,本研究的发现可能提供新的假设。
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来源期刊
CiteScore
2.10
自引率
10.50%
发文量
317
审稿时长
2 months
期刊介绍: Reproduction, Fertility and Development is an international journal for the publication of original and significant contributions on vertebrate reproductive and developmental biology. Subject areas include, but are not limited to: physiology, biochemistry, cell and molecular biology, endocrinology, genetics and epigenetics, behaviour, immunology and the development of reproductive technologies in humans, livestock and wildlife, and in pest management. Reproduction, Fertility and Development is a valuable resource for research scientists working in industry or academia on reproductive and developmental biology, clinicians and veterinarians interested in the basic science underlying their disciplines, and students. Reproduction, Fertility and Development is the official journal of the International Embryo Technology Society and the Society for Reproductive Biology. Reproduction, Fertility and Development is published with the endorsement of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the Australian Academy of Science.
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