Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

Area of Science:

• Endocrinology
• Reproductive Biology
• Toxicology

Background:

• Anabolic-androgenic steroid (AAS) abuse, including nandrolone decanoate (ND), is prevalent among athletes.
• Potential adverse effects on male reproductive health, such as suppressed testosterone production and testicular damage, are a significant concern.

Purpose of the Study:

• To investigate the impact of nandrolone decanoate (ND) on testosterone biosynthesis and testicular morphology in trained and sedentary mice.
• To elucidate the molecular mechanisms underlying ND-induced testicular dysfunction, focusing on steroidogenic enzymes and the blood-testis barrier (BTB).

Main Methods:

• Mice models (trained and sedentary) were treated with ND or vehicle for 6 weeks.
• Testosterone levels were quantified using liquid chromatography-mass spectrometry.
• Gene and protein expression of steroidogenic enzymes and BTB components were analyzed via Western blot and qRT-PCR.
• Testicular morphology was assessed using immunohistochemistry and immunofluorescence.

Main Results:

• Moderate to high ND doses significantly reduced serum testosterone levels.
• ND altered the expression of key enzymes involved in testosterone biosynthesis.
• ND induced BTB degradation by targeting tight junction protein-1 (TJP1).
• ND deregulated metalloproteinases (MMP-2, MMP-9) and caused mucin-1 mislocalization.

Conclusions:

• ND abuse impairs testosterone production and testicular integrity.
• ND disrupts the BTB, potentially through TJP1 internalization and MMP-2 deregulation.
• ND use poses risks for male infertility and low endogenous testosterone levels.