# Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice

## TL;DR

This study shows that QSOX2 is essential for proper ovarian function in mice, as its deletion disrupts ovulation and prevents pregnancy.

## Contribution

The study is the first to demonstrate the role of QSOX2 in female reproduction through targeted gene deletion in mice.

## Key findings

- QSOX2 is present in follicle-supporting cells but absent in the corpus luteum.
- Qsox2 knockout in females disrupts ovulation and prevents pregnancy.
- RNAseq analysis shows altered signaling pathways in Qsox2 knockout ovaries.

## Abstract

Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function.

We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions.

Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

The online version contains supplementary material available at 10.1186/s13048-024-01388-2.