Lhx9 haploinsufficiency alters transcription in the adult mouse ovary, causing subfertility and abnormal epithelium

Understanding the molecular pathways that underpin ovarian development and function is vital for improving the research approaches to investigating fertility. Despite a significant improvement in our knowledge of molecular activity in the ovary, many questions remain unanswered in the quest to understand factors influencing fertility and ovarian pathologies such as cancer. Here we present an investigation into the expression and function of developmental transcription factor LIM Homeobox 9 (LHX9) in the adult mouse ovary. We have characterised Lhx9 expression in several cell types of the mature ovary across follicle stages. To elucidate the function of this expression, we carried out an investigation of ovarian anatomy and transcription in a Lhx9+/- knockout mouse model displaying subfertility. Despite a lack of gross anatomical differences between genotypes, RNA-sequencing found that 90 genes were differentially expressed between Lhx9+/- and Lhx9+/+ mice. Gene ontology analyses revealed a downregulation of genes with major roles in ovarian steroidogenesis and an upregulation of genes with implications for ovarian cancer. Analysis of the ovarian epithelium revealed Lhx9+/- mice have a disorganised epithelial phenotype and a significant increase in epithelial marker gene expression. These results provide an analysis of Lhx9 in the adult mouse ovary and a new candidate for fertility research and ovarian epithelial cancer. Summary sentenceLhx9 haploinsufficient mice are subfertile with altered expression of steroid genes in the adult ovary and abnormal ovarian surface epithelium.