UXT in Sertoli cells is required for blood–testis barrier integrity†

Author:

Thomas Phillip A1,Schafler Eric D1,Ruff Sophie E23,Voisin Maud3,Ha Susan2,Logan Susan K12

Affiliation:

1. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA

2. Department of Urology, New York University School of Medicine, New York, NY, USA

3. Department of Microbiology, New York University School of Medicine, New York, NY, USA

Abstract

AbstractSpermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell’s ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood–testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT’s role in Sertoli cells and its contribution to the structural integrity of the BTB.

Funder

National Institutes of Health

Howard Hughes Medical Institute Gilliam Fellowship

Ford Foundation Fellowship

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,General Medicine,Reproductive Medicine

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