Olanzapine induced reproductive toxicity in male rats

Abstract

Although it is reported that olanzapine (OLZ), which is an atypical antipsychotic drug, causes sexual dysfunction in men, it is noteworthy that there is not any study evaluating the toxic effects of OLZ on the male reproductive system. In the scope of this research, it was aimed to assess the reproductive toxic effects of OLZ by oral administration of 2.5, 5, or 10 mg/kg of it to male rats for 28 days. For this purpose, sperm concentration, motility and morphology, and DNA damage were determined, and histopathological examination of testis tissue was carried out in rats. Also, the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, which play roles in the regulation of reproductive functions, and the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) which play roles in reproductive pathologies as oxidative stress biomarkers, were determined. According to the results, normal sperm morphology was decreased in 5 ve 10 mg/kg OLZ-administered groups, and pathological findings were evident in the testicular structure of the OLZ-administered group when compared with the control group. It was determined that serum LH, FSH, and testosterone levels were decreased in the OLZ-administered group. Also, decreases of GSH levels in testis tissue were determined and evaluated as the markers of the oxidative stress induced by OLZ in the testis. In conclusion, it was determined that reproductive toxic effects were induced in rats by OLZ administration. This pathology was accompanied by alterations of the hormone levels and testicular oxidative stress.

Antipsychotics increase steroidogenic enzyme gene expression in the rat brainstem

“…adrenal glands and testes, as steroids can easily pass through the blood–brain barrier. For instance, olanzapine and to a lesser extent aripiprazole administration may directly decrease FSH, LH and testosterone levels and disturb spermatogenesis in male rats [ 24 ]. This effect may potentially be related with an inhibition of 3-βHSD activity in the Leydig cells.…”

Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis

“…The results of our current study show that clozapine, sertindole and ziprasidone caused changes in the seminiferous epithelium and affected stages of spermatogenesis. According to Ardiç and coworkers (2021) olanzapine also caused histopathological changes in rat testes [ 21 ]. The authors found disorganisation within seminiferous tubules (swelling of Leydig cells and intracytoplasmic vacuolisation of Sertoli’s cells in testicular parenchyma), exfoliation and degeneration of germ cells.…”

“…The authors found disorganisation within seminiferous tubules (swelling of Leydig cells and intracytoplasmic vacuolisation of Sertoli’s cells in testicular parenchyma), exfoliation and degeneration of germ cells. Olanzapine affected sperm morphology but did not affect sperm motility [ 21 ].…”

“…Other antipsychotics also impair antioxidant enzyme activity. Olanzapine increased SOD activity whilst decreasing glutathione in rat testicles, related to abnormal sperm morphology and histopathological changes [ 21 ]. Risperidone also decreased glutathione, reduced semen quality and induced histopathological changes [ 29 ].…”

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“…The unusual morphologies percent was established. Considerably, the cytoplasmic leftover of sperms was considered as an unusual morphology 24 . The abnormality is seen in the head, middle piece, and tail of spermatozoa was noticed and categorized accordingly.…”