Poster Presentation 16th Asian Conference on Transcription 2019

Haploinsufficiency of  LIM Homeobox 9 (Lhx9) during genital ridge development impacts ovarian function and infertility (1097)

Stephanie Workman 1 , Megan Wilson 1
  1. The University of Otago, Dunedin, OTAGO, New Zealand

The network of transcription factors that regulate the development of the reproductive progenitor tissue, the genital ridge, is complex, with only a handful of genes identified as being vital for its formation. Given that the genital ridge will form a majority of the tissues of both the male and female reproductive systems, it is imperative that we characterise the transcriptional regulation of its development if we are to understand abnormalities that arise in disorders of sex development and infertility.

One transcription factor identified as being vital for genital ridge development is LIM Homeobox 9 (Lhx9). Knockout mouse models fail to form gonads, while heterozygous models exhibit reduced fertility and altered ovarian structure. RNA-sequencing and RT-qPCR analysis show altered expression of important cell markers and transcriptional regulators of ovarian function in heterozygous mice compared to wildtype littermates.

Interestingly Lhx9 displays sex dimorphic expression in the genital ridge prior to Sry gene expression. We hypothesised that this differential mRNA expression was due to methylation patterns established early in development, as previous publications have identified methylation differences at these sites in other tissues. Targeted methylation analysis of three CpG islands associated with the Lhx9 promoter revealed that the average methylation level was significantly greater in males, correlating with mRNA expression being higher in females.

Future characterisation of the differences in Lhx9 function between males and females will be carried out using ChIP sequencing. A more in depth analysis of the impact on ovarian function via oocyte counting is underway.