Testicular Gene Expression Response to Icacina Trichantha Root Ethanol Extract Therapy in Paroxetine-Induced Reproductive Dysfunction in Male Wistar Rats

Abstract

Male infertility is increasingly linked to pharmacological agents, particularly selective serotonin reuptake inhibitors (SSRIs) such as paroxetine, which may disrupt spermatogenesis through endocrine and molecular mechanisms. Paroxetine is therefore used as an agent in studying some intervention strategy in male infertility in experimental animals.  This study investigated the effects of paroxetine on the expression of key spermatogenic genes, cyclic AMP response element modulator (CREM), protamine I (PRM I), and protamine II (PRM II) in male Wistar rats and evaluated the remedial potential of Icacina trichantha root ethanol extract (ITREE) in comparison wDith tadalafil and clomiphene citrate. Twenty-five rats were randomly assigned to five groups: control (Group A), paroxetine only (Group B), paroxetine + ITREE (Group C), paroxetine + tadalafil (Group D), and paroxetine + clomiphene (Group E). The oral treatment regimen spans through 56 days. Paroxetine significantly increased CREM (92.64 ± 2.35 vs. 28.80 ± 2.94), PRM I (58.17 ± 1.73 vs. 21.64 ± 1.29), and PRM II (66.08 ± 3.25 vs. 42.74 ± 1.91) compared with control, and elevated the PRM I/PRM II ratio from 0.51 in control to 0.88. Co-administration of ITREE partially restored expression levels (CREM 68.87 ± 1.46, PRM I 42.15 ± 1.63, PRM II 55.71 ± 3.28) and attenuated the PRM I/PRM II ratio to 0.76. Tadalafil and clomiphene produced varying degrees of modulation, with CREM expression of 66.96 ± 2.07 and 105.12 ± 3.85, respectively. These findings indicate that paroxetine disrupted spermatid differentiation and chromatin remodeling, while ITREE effectively mitigates these molecular alterations. The study highlights the therapeutic potential of I. trichantha roots in preventing SSRI-induced male reproductive toxicity and provides a molecular basis for plant-based interventions.

Keywords:  Paroxetine, Spermatogenesis, CREM, Protamines, Icacina trichantha