Neurogenetics, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany.
Department of Anatomy, University Hospital, University Duisburg-Essen, Hufelandstr. 55, D-45147 Essen, Germany.
Int J Mol Sci. 2023 Dec 22;25(1):177. doi: 10.3390/ijms25010177.
Male reproduction depends on hormonally driven behaviors and numerous genes for testis development and spermatogenesis. Neuroplastin-deficient () male mice cannot sire offspring. By immunohistochemistry, we characterized neuroplastin expression in the testis. Breeding, mating behavior, hormonal regulation, testicular development, and spermatogenesis were analyzed in cell-type specific neuroplastin mutant mice. Leydig, Sertoli, peritubular myoid, and germ cells express Np, but spermatogenesis and sperm number are not affected in males. Neuroplastin lack from CNS neurons or restricted to spermatogonia or Sertoli cells permitted reproduction. Normal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) blood levels in males support undisturbed hormonal regulation in the brain. However, males lack mounting behavior accompanied by low testosterone blood levels. Testosterone rise from juvenile to adult blood levels is absent in males. LH-receptor stimulation raising intracellular Ca in Leydig cells triggers testosterone production. Reduced Plasma Membrane Ca ATPase 1 (PMCA1) in Leydig cells suggests that Leydig cells produce sufficient testosterone for testis and sperm development, but a lack of PMCA-Np complexes prevents the increase from reaching adult blood levels. Behavioral immaturity with low testosterone blood levels underlies infertility of males, revealing that Np is essential for reproduction.
雄性生殖依赖于激素驱动的行为和许多基因，这些基因对于睾丸发育和精子发生至关重要。神经粘连蛋白缺失（）的雄性小鼠无法生育后代。通过免疫组织化学，我们对睾丸中的神经粘连蛋白表达进行了特征描述。在细胞类型特异性神经粘连蛋白突变小鼠中分析了繁殖、交配行为、激素调节、睾丸发育和精子发生。Leydig、Sertoli、小管周肌样细胞和生殖细胞表达 Np，但在 雄性小鼠中，精子发生和精子数量不受影响。CNS 神经元中缺乏神经粘连蛋白或仅限于精原细胞或 Sertoli 细胞的缺失允许繁殖。正常的黄体生成素（LH）和卵泡刺激素（FSH）血液水平支持脑中未受干扰的激素调节。然而， 雄性小鼠缺乏伴随着低睾酮血液水平的交配行为。 雄性小鼠的睾酮从青少年到成年血液水平的升高是不存在的。LH 受体刺激在 Leydig 细胞中引发细胞内 Ca 的升高，从而触发睾酮的产生。 减少的 Plasma Membrane Ca ATPase 1（PMCA1）在 Leydig 细胞中表明， Leydig 细胞产生足够的睾酮用于睾丸和精子发生，但缺乏 PMCA-Np 复合物可防止其增加达到成年血液水平。低睾酮血液水平的行为不成熟是 雄性小鼠不育的基础，这表明 Np 对于生殖至关重要。
