Surgery, Murdoch Children's Research Institute, Melbourne, Australia.
Surgery, Murdoch Children's Research Institute, Melbourne, Australia; University of Melbourne, Melbourne, Australia; Urology Department, The Royal Children's Hospital, Parkville, Australia.
J Pediatr Surg. 2022 Mar;57(3):479-487. doi: 10.1016/j.jpedsurg.2021.05.007. Epub 2021 May 24.
BACKGROUND/PURPOSE: What causes normal descent of the testis in a fetus, and what goes wrong with this complex process to cause undescended testes (UDT), or cryptorchidism? Over the last 2 decades, most authors searching for the cause(s) of UDT have looked at the 2 main hormones involved, insulin-like hormone 3 (Insl3) and testosterone (T)/ dihydrotestosterone (DHT), and their known upstream (hypothalamic-pituitary axis) and intracellular 'downstream' pathways. Despite these detailed searches, the genetic causes of UDT remain elusive, which suggest the aetiology is multifactorial, and/or we are looking in the wrong place.
In this review we highlight the intricate morphological steps involved in testicular descent, which we propose may contain the currently 'idiopathic' causes of UDT. By integrating decades of research, we have underlined many areas that have been overlooked in the search for causes of UDT.
It is quite likely that the common causes of UDT are still hidden in these areas, and we suggest examining these processes is worthwhile in the hope of finding the common genetic anomalies that lead to cryptorchidism. Given the fact that a fibrous barrier preventing descent is often described at orchidopexy, examination of the extracellular matrix enzymes needed to allow gubernacular migration may be a fruitful place to start.
This review of the complex anatomical steps and hormonal regulation of testicular descent highlights many areas of morphology and signalling pathways that have been overlooked in the search for causes of UDT.
背景/目的：是什么导致胎儿的睾丸正常下降，而导致未降睾丸（UDT）或隐睾的复杂过程中出了什么问题？在过去的 20 年中，大多数寻找 UDT 原因的作者都研究了涉及的 2 种主要激素，胰岛素样激素 3（Insl3）和睾酮（T）/二氢睾酮（DHT），以及它们已知的上游（下丘脑-垂体轴）和细胞内“下游”途径。尽管进行了这些详细的搜索，但 UDT 的遗传原因仍难以捉摸，这表明病因是多因素的，或者我们的研究方向有误。
在这篇综述中，我们强调了睾丸下降所涉及的复杂形态步骤，我们提出这些步骤可能包含 UDT 目前“特发性”的原因。通过整合几十年来的研究，我们强调了许多在寻找 UDT 病因时被忽视的领域。
很可能 UDT 的常见原因仍隐藏在这些领域中，我们建议检查这些过程是值得的，希望能找到导致隐睾的常见遗传异常。鉴于在orchidopexy 时经常描述阻止下降的纤维屏障，检查允许精索迁移所需的细胞外基质酶可能是一个有成效的起点。
对睾丸下降的复杂解剖步骤和激素调节的综述强调了许多在寻找 UDT 病因时被忽视的形态和信号通路领域。
