Basciani Sabrina, Mariani Stefania, Arizzi Mario, Brama Marina, Ricci Andrea, Betsholtz Christer, Bondjers Cecilia, Ricci Giulia, Catizone Angela, Galdieri Michela, Spera Giovanni, Gnessi Lucio
Department of Medical Pathophysiology, University of Rome "La Sapienza," Policlinico Umberto I, 00161 Rome, Italy.
Biol Reprod. 2004 Jan;70(1):168-77. doi: 10.1095/biolreprod.103.019232. Epub 2003 Oct 1.
The platelet-derived growth factor (PDGF) family of ligands and receptors play a pivotal role in the development of various organs. The critical importance of the PDGF-mediated signaling during embryonic development and adult physiology of the kidney and the common mesonephric origin of the epididymis and kidney prompted us to investigate the immunohistochemical localization of PDGF A- and B-chain and PDGF receptor (PDGFR) alpha- and beta-subunit in rat and mouse epididymis, the expression profiles of the corresponding mRNAs, and the consequences of a loss-of-function mutation at the PDGF-A, PDGF-B, and PDGFR-beta loci on mouse epididymis phenotypic appearance. Prenatally, PDGF-A and PDGFR-alpha immunohistochemical staining was seen in both species, whereas PDGF-B and PDGFR-beta were absent. The cellular localization of PDGF-A within the epithelium and the alpha-receptor in the mesenchyme in either mouse or rat before birth suggests that the PDGF-A/PDGFR-alpha system might be involved in the epididymal epithelial-mesenchymal interaction during the fetal period of life. Postnatally, PDGF A- and B-ligand and PDGFR alpha- and beta-subunit were confined in the epithelium. The identity of PDGF and PDGFR proteins were further confirmed by immunoblotting. In line with the immunohistochemical studies, PDGF-A and PDGFR-alpha mRNAs were seen by reverse transcription-polymerase chain reaction in rat and mouse tissue before birth, whereas PDGF-B and PDGFR-beta were almost not detectable. During the first days of life, PDGF-B and PDGFR-beta genes started to appear, and the overall trend in mRNA expression throughout postnatal development showed that the transcripts levels for PDGF-A, PDGF-B, PDGFR-beta, and PDGFR-alpha were constant with the only exception of a progressive decrease of PDGFR-alpha in adult rats. The PDGF-A null mutation strongly influenced the epididymal phenotype starting from puberty; only fetal PDGF-B and PDGFR-beta -/- mice were available, and no differences were seen in the epididymis of these animals, compared with wild-type littermates. Taken together, these data indicate that the PDGF system is highly expressed in the epididymis and suggest that PDGF could be involved in the maintenance of morphological structure and functional control of this organ.
血小板衍生生长因子（PDGF）配体和受体家族在各种器官的发育中起着关键作用。PDGF介导的信号传导在胚胎发育以及肾脏的成年生理过程中至关重要，且附睾和肾脏具有共同的中肾起源，这促使我们研究大鼠和小鼠附睾中PDGF A链和B链以及PDGF受体（PDGFR）α和β亚基的免疫组织化学定位、相应mRNA的表达谱，以及PDGF - A、PDGF - B和PDGFR - β基因座功能缺失突变对小鼠附睾表型外观的影响。在产前，两种物种均可见PDGF - A和PDGFR - α免疫组织化学染色，而PDGF - B和PDGFR - β则未检测到。出生前，无论是小鼠还是大鼠，PDGF - A在上皮内的细胞定位以及α受体在间充质中的定位表明，PDGF - A/PDGFR - α系统可能在胎儿期参与附睾上皮 - 间充质相互作用。出生后，PDGF A链和B链配体以及PDGFR α和β亚基局限于上皮。通过免疫印迹进一步证实了PDGF和PDGFR蛋白的一致性。与免疫组织化学研究一致，出生前在大鼠和小鼠组织中通过逆转录 - 聚合酶链反应可检测到PDGF - A和PDGFR - α mRNA，而PDGF - B和PDGFR - β几乎无法检测到。在出生后的头几天，PDGF - B和PDGFR - β基因开始出现，并且在整个出生后发育过程中mRNA表达的总体趋势表明，除成年大鼠中PDGFR - α逐渐减少外，PDGF - A、PDGF - B、PDGFR - β和PDGFR - α的转录水平保持恒定。PDGF - A基因无效突变从青春期开始强烈影响附睾表型；仅获得了胎儿期PDGF - B和PDGFR - β基因敲除小鼠，与野生型同窝小鼠相比，这些动物的附睾未见差异。综上所述，这些数据表明PDGF系统在附睾中高度表达，并提示PDGF可能参与该器官形态结构的维持和功能控制。
