Department of Anatomy, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Department of Anatomy, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Reprod Toxicol. 2021 Jun;102:56-66. doi: 10.1016/j.reprotox.2021.03.008. Epub 2021 Apr 15.
Neonatal maternal separation (NMS) is an experimental model for early life stress, which affects the growth and development of various organs, resulting in adverse health effects in humans and animals. In our previous study, we demonstrated that NMS [(0.5-, 1-, 2-h/day NMS, from postnatal day (PND) 1-10] induced morphological changes to the male reproductive system, including decreased Sertoli cell numbers in mouse testes at PND 70. To clarify the mechanism by which NMS decreases Sertoli cell numbers, we evaluated the effects of NMS on mouse testes at PNDs 10 and 16. At PND 10, the Sertoli cell number was not significantly different among experimental groups; however, it decreased in 0.5- and 2-h/day NMS mice at PND 16. The termination of Sertoli cell proliferation in prepuberty can be induced by p27, a cyclin-dependent kinase inhibitor. At PND 10, we observed an increase in the number of p27-positive Sertoli cells in 2-h/day NMS mice. The seminiferous tubule diameters decreased significantly in 1- and 2-h/day NMS mice, and the relative interstitial area increased in 2-h/day NMS mice. Serum corticosterone level significantly increased, and serum testosterone level significantly decreased in the 2-h/day NMS mice. At PND 16, the tubule diameters and height of seminiferous epithelium were significantly higher in 0.5- and 2-h/day NMS mice. Our results suggest that NMS disturbs serum corticosterone and testosterone levels and increases the number of p27-positive Sertoli cells at PND 10, resulting in a decrease in the number of Sertoli cells at PND 16.
新生期母体分离（NMS）是一种早期生活应激的实验模型，它会影响各种器官的生长和发育，导致人类和动物的健康受到不良影响。在我们之前的研究中，我们证明了 NMS（[0.5-、1-、2 小时/天 NMS，从新生后第 1 天（PND）1-10 天]）会导致雄性生殖系统的形态变化，包括在 PND70 时雄性小鼠睾丸中支持细胞数量减少。为了阐明 NMS 减少支持细胞数量的机制，我们在 PND10 和 PND16 时评估了 NMS 对雄性小鼠睾丸的影响。在 PND10 时，实验组之间支持细胞数量没有显著差异；然而，在 0.5-和 2 小时/天 NMS 组中，支持细胞数量在 PND16 时减少。p27（一种细胞周期蛋白依赖性激酶抑制剂）可诱导青春期前支持细胞增殖的终止。在 PND10 时，我们观察到 2 小时/天 NMS 组中 p27 阳性支持细胞数量增加。1-和 2 小时/天 NMS 组的生精小管直径显著减小，2 小时/天 NMS 组的相对间质面积增加。血清皮质酮水平显著升高，2 小时/天 NMS 组血清睾酮水平显著降低。在 PND16 时，0.5-和 2 小时/天 NMS 组的小管直径和生精上皮高度显著增加。我们的结果表明，NMS 会干扰血清皮质酮和睾酮水平，并在 PND10 时增加 p27 阳性支持细胞的数量，从而导致 PND16 时支持细胞数量减少。
