Carosi Sara, Innocenti Federica, Monaco Lucia, Laurenzi Gaia, Saracino Rossana, Canipari Rita, Vicini Elena
Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, Rome, Italy.
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Mol Reprod Dev. 2025 Jan;92(1):e70012. doi: 10.1002/mrd.70012.
A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs. However, the proteolytic activity results from a balance between enzyme activity and inhibitors. Hormonal stimulation decreased the expression of the inhibitor PAI-1, suggesting that the increase in proteolytic activity might depend on the decreased production of PAI-1. The expression of the two enzymes and their inhibitor depends on the seminiferous epithelium stage. We observed higher uPA mRNA levels at stages VII-VIII and IX-XII, tPA peaks at stages VII-VIII, and PAI-1 mRNA levels decreased at stages VII-VIII and IX-XII. The testes from mice lacking the uPA gene (uPA) presented statistically smaller sizes and weights. Histological analysis of uPAanimals showed tubular morphology defects and atypical residual bodies (RB), suggesting a defect in Sertoli cell phagocytosis. Moreover, we show lower sperm concentration and motility in uPA mice. These data suggested an effective deficiency of testicular development in the absence of uPA.
考虑到哺乳动物性腺在发育过程中经历的复杂形态发生过程，有人推测纤溶酶原激活剂（PA）系统在其中发挥作用。我们的研究结果表明，在基础条件下，小鼠支持细胞会产生两种类型的PA，即组织型PA（tPA）和尿激酶型PA（uPA），激素处理会增加这两种酶的产生。酶分泌的增加与其mRNA的平行增加并不相关。然而，蛋白水解活性是由酶活性和抑制剂之间的平衡产生的。激素刺激降低了抑制剂PAI-1的表达，这表明蛋白水解活性的增加可能取决于PAI-1产生的减少。这两种酶及其抑制剂的表达取决于生精上皮阶段。我们观察到在VII-VIII期和IX-XII期uPA mRNA水平较高，tPA在VII-VIII期达到峰值，PAI-1 mRNA水平在VII-VIII期和IX-XII期下降。缺乏uPA基因（uPA）的小鼠的睾丸在统计学上尺寸和重量更小。对uPA基因敲除小鼠的组织学分析显示出管状形态缺陷和非典型残留小体（RB），表明支持细胞吞噬功能存在缺陷。此外，我们发现uPA基因敲除小鼠的精子浓度和活力较低。这些数据表明在缺乏uPA的情况下，睾丸发育存在有效缺陷。
