Paternal Finasteride Treatment Can Influence the Testicular Transcriptome Profile of Male Offspring-Preliminary Study.

Agnieszka Kolasa,Dorota Rogińska,Bogusław Machaliński,Sylwia Rzeszotek,Barbara Wiszniewska

doi:10.3390/cimb43020062

Agnieszka Kolasa, Dorota Rogińska + Show 3 more

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https://doi.org/10.3390/cimb43020062

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Abstract

(1) Background: Hormone-dependent events that occur throughout spermatogenesis during postnatal testis maturation are significant for adult male fertility. Any disturbances in the T/DHT ratio in male progeny born from females fertilized by finasteride-treated male rats (F0:Fin) can result in the impairment of testicular physiology. The goal of this work was to profile the testicular transcriptome in the male filial generation (F1:Fin) from paternal F0:Fin rats. (2) Methods: The subject material for the study were testis from immature and mature male rats born from females fertilized by finasteride-treated rats. Testicular tissues from the offspring were used in microarray analyses. (3) Results: The top 10 genes having the highest and lowest fold change values were mainly those that encoded odoriferous (Olfr: 31, 331, 365, 633, 774, 814, 890, 935, 1109, 1112, 1173, 1251, 1259, 1253, 1383) and vomeronasal (Vmn1r: 50, 103, 210, 211; Vmn2r: 3, 23, 99) receptors and RIKEN cDNA 5430402E10, also known as odorant-binding protein. (4) Conclusions: Finasteride treatment of male adult rats may cause changes in the testicular transcriptome of their male offspring, leading to a defective function of spermatozoa in response to odorant-like signals, which are recently more and more often noticed as significant players in male fertility.

Highlights

Without a doubt, the morphology and function of the male gonad are controlled by the hypothalamic–pituitary–gonad axis and locally produced androgens—testosterone (T) and more biologically active dihydrotestosterone (DHT) [1]
Any disturbances in the T/DHT ratio in male progeny born from females fertilized by finasteride-treated male rats (F0:Fin) can result in the impairment of testicular physiology
In the 1990s, finasteride was introduced to medical care and was considered a safe drug, without any “side effects” on male fertility, and this view is still maintained among dermatologists [7,8]

Summary

Introduction

The morphology and function of the male gonad are controlled by the hypothalamic–pituitary–gonad axis and locally produced androgens—testosterone (T) and more biologically active dihydrotestosterone (DHT) [1]. One year after the cessation of finasteride treatment, the meiotic pattern did not change, and elevated diploidy and sex chromosome disomy were still present; motility and sperm morphology were improved [17]. This so-called post-finasteride syndrome (PFS) was recently added to the list of genetic and rare diseases by the United States National Institutes of Health (NIH) [18,19]

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