Wen Qing, Cheng C Yan, Liu Yi-Xun
State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York 10065, United States.
Semin Cell Dev Biol. 2016 Nov;59:89-98. doi: 10.1016/j.semcdb.2016.03.003. Epub 2016 Mar 8.
During fetal testis development, fetal Leydig cells (FLCs) are found to be originated from multiple progenitor cells. FLC specification and function are under tight regulation of specific genes and signaling proteins. Furthermore, Sertoli cells play a crucial role to regulate FLC differentiation during fetal testis development. FLC progenitor- and FLC-produced biomolecules are also involved in the differentiation and activity of rodent FLCs. The main function of FLCs is to produce androgens to masculinize XY embryos. However, FLCs are capable of producing androstenedione but not testosterone due to the lack of 17β-HSD (17β-hydroxysteroid dehydrogenase), but fetal Sertoli cells express 17β-HSD which thus transforms androstenedione to testosterone in the fetal testis. On the other hand, FLCs produce activin A to regulate Sertoli cell proliferation, and Sertoli cells in turn modulate testis cord expansion. It is now generally accepted that adult Leydig cells (ALCs) gradually replace FLCs during postnatal development to produce testosterone to support spermatogenesis as FLCs undergo degeneration in neonatal and pre-pubertal testes. However, based on studies using genetic tracing mouse models, FLCs are found to persist in adult testes, making up ∼20% of total Leydig cells. In this review, we evaluate the latest findings regarding the development, function and fate of FLCs during fetal and adult testis development.
在胎儿睾丸发育过程中，发现胎儿睾丸间质细胞（FLCs）起源于多个祖细胞。FLCs的特化和功能受到特定基因和信号蛋白的严格调控。此外，支持细胞在胎儿睾丸发育过程中对FLCs的分化起着关键的调节作用。FLC祖细胞和FLC产生的生物分子也参与了啮齿动物FLCs的分化和活性调节。FLCs的主要功能是产生雄激素，使XY胚胎男性化。然而，由于缺乏17β-羟类固醇脱氢酶（17β-HSD），FLCs能够产生雄烯二酮但不能产生睾酮，而胎儿支持细胞表达17β-HSD，因此在胎儿睾丸中将雄烯二酮转化为睾酮。另一方面，FLCs产生激活素A来调节支持细胞的增殖，而支持细胞反过来调节睾丸索的扩张。目前普遍认为，在出生后发育过程中，成年睾丸间质细胞（ALCs）逐渐取代FLCs以产生睾酮来支持精子发生，因为FLCs在新生儿和青春期前睾丸中会发生退化。然而，基于使用基因追踪小鼠模型的研究，发现FLCs在成年睾丸中持续存在，占睾丸间质细胞总数的约20%。在这篇综述中，我们评估了关于胎儿和成年睾丸发育过程中FLCs的发育、功能和命运的最新研究结果。
