# Loss of Function of the Zxdb Gene Leads to a Decrease in the Decidualization Rate and Number of Pups Born in Mice by Affecting the Expression of the Cell Adhesion Molecules

## TL;DR

This study shows that the Zxdb gene in mice is important for female fertility, as its loss reduces embryo implantation and litter size.

## Contribution

The study is the first to link Zxdb gene loss to reduced female fertility in mice through disrupted cell adhesion.

## Key findings

- Loss of Zxdb in mice reduces decidualization rates and litter size.
- Zxdb loss affects adhesion molecule expression in uterine tissue.
- Disordered adhesion molecules may cause lower embryo implantation rates.

## Abstract

The Zinc Finger X-Linked Duplicate B (ZXDB) gene is one of a pair of replicated zinc finger genes on chromosome Xp11.21. The homologous gene of ZXDB in mice is Zxdb. Recent studies have found that Zxdb plays a role in the spermatogenic process of mice; however, its impact on the female reproductive system has not yet been explored. In our study, we found, for the first time, that the loss of function of Zxdb leads to reduced decidualization rates and a decrease in litter size in female mice. Secondly, we found that maternal loss of Zxdb is the determinant of these phenotypes. Thirdly, the transcriptional and proteomic differential expression genes in the uterine tissues of wild-type (WT) and Zxdb knockout (Zxdb-KO) mice were significantly enriched in signaling pathways such as adhesion molecules. Finally, we demonstrated that the disorder of expression and uneven distribution of adhesion molecules in mouse uterine tissue may be the main reason for the decline in embryo implantation rate. In conclusion, we have established for the first time a link between the Zxdb gene and reduced female fertility. This study will help provide guidance and genetic counseling for future common clinical complications such as Recurrent Spontaneous Abortion (RSA) or Recurrent Implantation Failure (RIF).