School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20814, USA.
Development. 2024 Nov 15;151(22). doi: 10.1242/dev.204319. Epub 2024 Nov 19.
Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal, but fertility declines with age. Although morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis. All testes contained spermatogonia, but we observed a progressive decline in spermatogenesis that correlated with age. Testes from some older males only contained spermatogonia and a reduced population of spermatocytes. Spermatogonia in older males were transcriptionally distinct from spermatogonia in testes capable of robust spermatogenesis. Immune cells including macrophages and lymphocytes drastically increased in abundance in testes that could not complete spermatogenesis. Our developmental atlas reveals the cellular changes as the testis ages and defines a molecular roadmap for the regulation of spermatogenesis.
脊椎动物精原干细胞在动物的一生中维持精子的产生，但生育能力会随着年龄的增长而下降。尽管形态学研究为我们理解典型的精子发生提供了信息，但精子发生的维持和衰退的分子和细胞机制尚不清楚。我们使用单细胞 RNA 测序生成了衰老斑马鱼睾丸的发育图谱。所有睾丸都含有精原细胞，但我们观察到精子发生逐渐减少，这与年龄有关。一些老年雄性的睾丸仅含有精原细胞和数量减少的精母细胞。老年雄性的精原细胞在转录上与能够进行旺盛精子发生的睾丸中的精原细胞不同。包括巨噬细胞和淋巴细胞在内的免疫细胞在不能完成精子发生的睾丸中大量增加。我们的发育图谱揭示了随着睾丸衰老而发生的细胞变化，并为精子发生的调控定义了一个分子路线图。
