Neuroplastin Expression in Male Mice Is Essential for Fertility, Mating, and Adult Testosterone Levels

Area of Science:

• Neurobiology
• Reproductive Biology
• Molecular Endocrinology

Background:

• Male reproduction relies on hormonal regulation and specific genes for testicular function.
• Neuroplastin-deficient (Nptn) male mice exhibit infertility, unable to sire offspring.
• Understanding neuroplastin's role is crucial for male reproductive health.

Purpose of the Study:

• To investigate the role of neuroplastin (Np) in male reproductive functions.
• To characterize neuroplastin expression in testicular cells and its impact on fertility.
• To elucidate the mechanisms underlying infertility in Nptn male mice.

Main Methods:

• Immunohistochemistry to detect neuroplastin expression in testes.
• Analysis of breeding, mating behavior, hormonal profiles (LH, FSH, testosterone), testicular development, and spermatogenesis in Nptn mutant mice.
• Assessment of cell-type specific neuroplastin knockout effects on reproduction.

Main Results:

• Neuroplastin is expressed in Leydig, Sertoli, peritubular myoid, and germ cells.
• Spermatogenesis and sperm count remain unaffected in Nptn males.
• Nptn males display absent mounting behavior, low testosterone levels, and impaired testosterone rise, leading to infertility.
• Lack of neuroplastin in CNS neurons, spermatogonia, or Sertoli cells permits reproduction.
• Reduced Plasma Membrane Ca2+ ATPase 1 (PMCA1) in Nptn Leydig cells affects testosterone release.

Conclusions:

• Neuroplastin is essential for male reproduction, primarily impacting behavior and testosterone regulation.
• Infertility in Nptn males stems from behavioral immaturity and insufficient testosterone levels, not impaired spermatogenesis.
• Neuroplastin's role in Leydig cell function, potentially via PMCA-Np complexes, is critical for achieving adult testosterone levels necessary for reproduction.