Project Description

PLoS Genet. 2019 Jul 11;15(7):e1008062. doi: 10.1371/journal.pgen.1008062.

Reproduction disrupts stem cell homeostasis in testes of aged male Drosophila via an induced microenvironment


Author information

Yi Chieh Chang1,2, Hsin Tu2,3, Jing-Yi Chen2.4, Ching-Chin Chang1,2, Shu Yuan Yang1,2,5, Haiwei Pi1,2,3,4*.

  1. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  2. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  3. Craniofacial Research Center, Taoyuan Chang Gang Memorial Hospital, Taoyuan, Taiwan
  4. Molecular Medicine Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan



果蠅睾丸中的精原幹細胞(GSCs)和囊幹細胞(CySC)通常由 hub 細胞這個微環境維持幹細胞形成在睪丸的頂端區域。

在這項研究中,我們發現了在老化的個體中,交配繁殖會使Jun-N-terminal kinase(JNK) 訊號傳遞在囊細胞過度活化,造成在已分化的囊細胞中維持了自我更新基因的表達,使得CySCs和GSCs的早期分化子細胞累積在睪丸中。囊幹細胞中JNK訊號的活性對於維持囊幹細胞在睪丸的頂端是必須的。





Stem cells rely on instructive cues from their environment. Alterations in microenvironments might contribute to tissue dysfunction and disease pathogenesis. Germline stem cells (GSCs) and cyst stem cells (CySC) in Drosophila testes are normally maintained in the apical area by the testicular hub. In this study, we found that reproduction leads to accumulation of early differentiating daughters of CySCs and GSCs in the testes of aged male flies, due to hyperactivation of Jun-N-terminal kinase (JNK) signaling to maintain self-renewal gene expression in the differentiating cyst cells. JNK activity is normally required to maintain CySCs in the apical niche. A muscle sheath surrounds the Drosophila testis to maintain its long coiled structure. Importantly, reproduction triggers accumulation of the tumor necrosis factor (TNF) Eiger in the testis muscle to activate JNK signaling via the TNF receptor Grindelwald in the cyst cells. Reducing Eiger activity in the testis muscle sheath suppressed reproduction-induced differentiation defects, but had little effect on testis homeostasis of unmated males. Our results reveal that reproduction in males provokes a dramatic shift in the testicular microenvironment, which impairs tissue homeostasis and spermatogenesis in the testes.