Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia.
Reprod Sci. 2021 Oct;28(10):2916-2928. doi: 10.1007/s43032-021-00616-0. Epub 2021 May 18.
Cryptorchidism causes spermatogenic failure and reduced serum androgen levels, as well as testicular oedema and fibrosis, which are hallmarks of inflammation. However, the role of inflammation and the effects of cryptorchidism on Sertoli cell and Leydig cell function at the molecular level remain ill-defined. Bilateral cryptorchidism was surgically induced in adult rats for 7 and 14 weeks. Testis weights decreased to 40% of normal within 7 weeks, due to loss of all developing spermatogenic cells except spermatogonia, but did not decrease further at 14 weeks. Serum FSH and LH were increased at both time points, consistent with a loss of feedback by inhibin and testosterone. This damage was accompanied by progressive accumulation of interstitial fluid and peritubular fibrosis, and a progressive decline of several critical Sertoli cell genes (Sox9, Inha (inhbin α-subunit), Cldn11 (claudin 11), Gja1 (connexin 43), and Il1a (interleukin-1α)) and the Leydig cell steroidogenic enzymes, Cyp11a1, Hsd3b1, and Hs17b3. Activin B and the activin-binding protein, follistatin, also declined, but the intratesticular concentration of activin A, which is a regulator of inflammatory responses, was largely unaffected at either time point. Expression of genes involved in inflammation (Tnf, Il10, Il1b, Mcp1) and fibrosis (Acta2, Col1a1) were considerably elevated at both time points. These data indicate that induction of experimental cryptorchidism, which causes complete failure of spermatogenesis in the adult rat, also induces chronic testicular inflammation, manifesting in oedema and fibrosis, and a progressive decline of Sertoli and Leydig cell gene expression and function.
隐睾症会导致生精失败和血清雄激素水平降低，以及睾丸水肿和纤维化，这些都是炎症的标志。然而，炎症的作用以及隐睾症对支持细胞和间质细胞功能的影响在分子水平上仍未得到明确界定。通过手术诱导成年大鼠双侧隐睾 7 周和 14 周。睾丸重量在 7 周内降至正常的 40%，这是由于除精原细胞外所有发育中的生精细胞都丢失了，但在 14 周时并未进一步下降。血清 FSH 和 LH 在两个时间点都升高，这与抑制素和睾酮的反馈丧失一致。这种损伤伴随着间质液和小管周围纤维化的逐渐积累，以及一些关键支持细胞基因（Sox9、Inha（抑制素 α 亚单位）、Cldn11（闭合蛋白 11）、Gja1（连接蛋白 43）和 Il1a（白细胞介素-1α））和间质细胞类固醇生成酶 Cyp11a1、Hsd3b1 和 Hs17b3 的逐渐下降。激活素 B 和激活素结合蛋白，滤泡抑制素，也下降，但在这两个时间点，作为炎症反应调节剂的激活素 A 的睾丸内浓度基本上没有受到影响。参与炎症（Tnf、Il10、Il1b、Mcp1）和纤维化（Acta2、Col1a1）的基因的表达在两个时间点都显著升高。这些数据表明，实验性隐睾症的诱导，会导致成年大鼠的生精完全失败，也会引起慢性睾丸炎症，表现为水肿和纤维化，以及支持细胞和间质细胞基因表达和功能的逐渐下降。
