Sosa Enrique, Wamaitha Sissy E, Hsu Fei-Man, Lara Mary Jasmine D, Oyama Kiana, Custer Maggie, Murphy Melinda, Hennebold Jon D, Hwang Young Sun, Clark Amander T
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095.
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2419995122. doi: 10.1073/pnas.2419995122. Epub 2025 Jun 26.
The formation of bilateral testes in animals is critical for puberty, reproductive capacity, and testosterone production across the life course. In humans, testis development begins in embryonic life in the first trimester, with considerable effort focused on the cell and developmental events associated with testis cell specification, leaving limited knowledge on testicular organogenesis during the second and third trimesters. To fill this knowledge gap, we evaluated testicular cell maturation at weeks 5 (W5), W6, W8, W15, and W19 postconception using a rhesus macaque model. Our data identify a major transcriptional change in the somatic cells of the testis (Sertoli cells, interstitial cells and fetal Leydig cells) between W8 and W15, and this is associated with the maturation of seminiferous cords and maturation of PGCs into fetal spermatogonia. Through this work, we identified cellular changes and differential protein expression between W5 and W19 that can be used to holistically define testis development across the time course of embryonic and fetal life. This study provides important insights necessary to recreate the testicular niche from stem cells for biomedical research.
动物双侧睾丸的形成对于青春期、生殖能力以及整个生命过程中的睾酮生成至关重要。在人类中,睾丸发育始于妊娠前三个月的胚胎期,大量研究集中在与睾丸细胞特化相关的细胞和发育事件上,而关于妊娠中期和晚期睾丸器官发生的知识有限。为了填补这一知识空白,我们使用恒河猴模型评估了受孕后第5周(W5)、第6周、第8周、第15周和第19周时睾丸细胞的成熟情况。我们的数据表明,睾丸的体细胞(支持细胞、间质细胞和胎儿睾丸间质细胞)在W8和W15之间发生了主要的转录变化,这与生精索的成熟以及原始生殖细胞(PGC)成熟为胎儿精原细胞有关。通过这项工作,我们确定了W5和W19之间的细胞变化和差异蛋白表达,这些可用于全面定义胚胎和胎儿期整个时间过程中的睾丸发育。这项研究为从干细胞重建睾丸微环境用于生物医学研究提供了重要的见解。