The Shraga Segal Dept. of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Int J Mol Sci. 2021 Jan 24;22(3):1147. doi: 10.3390/ijms22031147.
Pigment epithelium derived factor (PEDF) is a multifunctional secretory soluble glycoprotein that belongs to the serine protease inhibitor (serpin) family. It was reported to have neurotrophic, anti-angiogenic and anti-tumorigenic activity. Recently, PEDF was found in testicular peritubular cells and it was assumed to be involved in the avascular nature of seminiferous tubules. The aim of this study was to determine the cellular origin, expression levels and target cells of PEDF in testicular tissue of immature and adult mice under physiological conditions, and to explore its possible role in the process of spermatogenesis in vitro. Using immunofluorescence staining, we showed that PEDF was localized in spermatogenic cells at different stages of development as well as in the somatic cells of the testis. Its protein levels in testicular homogenates and Sertoli cells supernatant showed a significant decrease with age. PEDF receptor (PEDF-R) was localized within the seminiferous tubule cells and in the interstitial cells compartment. Its RNA expression levels showed an increase with age until 8 weeks followed by a decrease. RNA levels of PEDF-R showed the opposite trend of the protein. Addition of PEDF to cultures of isolated cells from the seminiferous tubules did not changed their proliferation rate, however, a significant increase was observed in number of meiotic/post meiotic cells at 1000 ng/mL of PEDF; indicating an in vitro differentiation effect. This study may suggest a role for PEDF in the process of spermatogenesis.
色素上皮衍生因子（PEDF）是一种多功能分泌可溶性糖蛋白，属于丝氨酸蛋白酶抑制剂（serpin）家族。它具有神经营养、抗血管生成和抗肿瘤生成活性。最近，PEDF 被发现在睾丸小管周围细胞中，据推测它参与了精小管的无血管性质。本研究旨在确定生理条件下未成熟和成年小鼠睾丸组织中 PEDF 的细胞来源、表达水平和靶细胞，并探讨其在体外精子发生过程中的可能作用。通过免疫荧光染色，我们表明 PEDF 定位于发育不同阶段的生殖细胞以及睾丸体细胞中。其在睾丸匀浆和支持细胞上清液中的蛋白水平随年龄显著下降。PEDF 受体（PEDF-R）定位于生精小管细胞和间质细胞区室中。其 RNA 表达水平随年龄增加至 8 周后下降。PEDF-R 的 RNA 水平呈相反趋势。将 PEDF 添加到分离的生精小管细胞培养物中不会改变其增殖率，但在 1000ng/ml 的 PEDF 时观察到减数分裂/减数分裂后细胞数量显著增加；表明存在体外分化作用。本研究可能提示 PEDF 在精子发生过程中的作用。
