# The ER-associated degradation adaptor SEL1L is dispensable for ER homeostasis and the differentiation of spermatogenic cells

## TL;DR

This study shows that the protein SEL1L is not essential for maintaining the function of the endoplasmic reticulum or for the development of male reproductive cells.

## Contribution

The study reveals that SEL1L is not required for ER homeostasis or spermatogenesis in mice.

## Key findings

- SEL1L deletion in spermatogenic cells does not impair sperm count, motility, fertility, or testicular structure.
- SEL1L loss reduces HRD1 levels in spermatids but not in spermatocytes.
- SEL1L deficiency does not cause ER stress, ER dilation, or cell death in testes.

## Abstract

The SEL1L-HRD1 complex is a critical component of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway, essential for maintaining ER homeostasis and cellular function. While the crucial roles of SEL1L and HRD1 in various physiological processes have been reported in mice and humans, their specific functions in male germ cells remain unexplored. Here, we show that, while SEL1L is highly expressed in spermatogenic cells, it is dispensable for their differentiation and ER homeostasis. SEL1L deletion in these cells does not affect sperm count, motility, male fertility, or testicular histology. Mechanistically, our data show that SEL1L loss reduces HRD1 protein levels in spermatids but unexpectedly, not in spermatocytes. Furthermore, SEL1L deficiency does not induce overt ER stress response, ER dilation, or cell death in the testes. Collectively, these findings indicate that SEL1L is not required for ER homeostasis or the differentiation of male germ cells.