Protein associated with testicular ageing identified

Age-related changes in gene expression have revealed molecular clues about male fertility in new research.

Male reproductive tissues do not have an equivalent of menopause, but male fertility can decline over time, generally from age 45 onwards. Scientists in China have identified a protein which appears to play a key role in testicular ageing and male fertility.

'With advancing age, the testis undergoes profound structural alterations,' the authors from Shanghai Naval Medical University and the Chinese Key Laboratory of Cell Engineering in Shanghai explained in their paper published in the Journal of Molecular Cell Biology.

The team took testicular tissue samples from two young donors, aged 23 and 30, and two older donors, aged 61 and 91. They used the tissue to perform single-nucleus RNA sequencing on 10,000 cells, allowing them to understand which genes are being expressed in each individual cell.

They also analysed the chromatin structure in each cell. Chromatin is a protein which regulates DNA structure, controlling which genes are actively being expressed, and which are 'switched off' in a given cell.

Past research in the field has identified that two cell types in testes are particularly relevant to testicular ageing – Sertoli cells, which support sperm production, and Leydig cells, which produce testosterone. Communication between these cells is thought to be crucial for sperm production.

'We observed a widespread dysregulation in cell–cell interactions involving ageing Sertoli cells and Leydig cells,' the authors noted.

The gene expression analysis also revealed age-associated changes in how Sertoli cells interacted with immune cells, and how Leydig cells behaved in relation to hormone secretion and blood-vessel development.

In particular, the samples from older donors showed increased production of a protein called WLS, part of the Wnt molecular signalling pathway involved in stem cell maintenance and proliferation.

'WLS is central to the Wnt signalling pathway that governs stem cell self-renewal, differentiation, metabolism, survival, and proliferation,' said the authors. 'Despite its established roles, the specific function of WLS in testicular ageing remains unclear.'

To further explore the finding, the researchers expressed the WLS gene in lab-grown testis cells and found it correlated with signs of ageing. They speculate that WLS may not only be associated with testicular ageing, but may actually control it.

The authors of this study note that the sample size is small, mainly due to ethical and tissue availability constraints, and plan to progress the research as more tissue becomes available.