Early exposure to paracetamol reduces level of testicular testosterone and changes gonadal expression of genes relevant for steroidogenesis in rats offspring

Abstract

In this study, we investigated the effects of early paracetamol treatment on the testicular level of testosterone and expression of genes important for steroid biosynthesis and reproduction in male rats offspring. Rats were continuously exposed to paracetamol at doses of 5 or 15 mg/kg b.w. during pregnancy and the first two months of the postpartum development. Testosterone level was determined by ELISA. Profile of gene expression for the testicular steroidogenic factors were evaluated using the Real-Time PCR. Our results showed that paracetamol reduces testicular testosterone level and causes compensatory transactivation of genes important for steroidogenesis and reproductive capacity. We have observed significant over-expression of several genes involved in cholesterol transport and steroid biosynthesis e.g., genes for steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, luteinizing hormone subunit beta, gonadotropin and androgen receptors. Up-regulation of these genes with parallel testosterone reduction in the testicles could be the possible mechanism that maintains and prevents the loss of the steroidogenic function.

Keywords:

• Paracetamol
• acetaminophen
• prenatal
• testis
• testosterone
• mRNA

Acknowledgements

All authors approved the final manuscript. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Author contributions

Kamilla Blecharz-Klin: conceptualization, methodology, investigation, formal analysis, resources, data curation, writing – original draft supervision

Anna Sznejder-Pachołek: methodology, validation, formal analysis, investigation, data curation

Adriana Wawer: methodology, formal analysis, investigation, data curation

Justyna Pyrzanowska: investigation, methodology

Agnieszka Piechal: investigation, methodology

Ilona Joniec-Maciejak: methodology, validation

Dagmara Mirowska-Guzel: resources, writing – review & editing

Ewa Widy-Tyszkiewicz: conceptualization, investigation, writing – review & editing

Disclosure statement

The authors declare that they have no competing interests. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Additional information

Funding

Project implemented with CePT infrastructure was financed by the European Union – the European Regional Development Fund within the Operational Programme ‘Innovative economy’ for 2007–2013.