BackgroundDisorders of sex development (DSD) is a chronic autoimmune disease characterized by systemic in ammation, pathological osteogenesis, and endocrine abnormality. However, its genetic etiology remains mostly unknown. In addition, little research focuses on the regulation mechanism from the view of transcriptomics in the hypothalamic-pituitary-gonadal axis (HPGA). The hypothalamus is the integrated center of the HPGA mediating neural, hormonal, and environmental stimulus to sex development.
MethodsThree XX-DSD (SRY-negative) pig (DSD) and three NF pigs ( ve months old, 40 kg ± 5 kg) were selected by external genitalia observation and sex determining region Y gene (SRY) detection. The hypothalamus were sampled for RNA isolation, and the mRNA, lncRNA and miRNA expression pro les were analyzed by sequencing.
ResultsA total of 1,258 lncRNAs, 1,086 mRNAs, and 61 microRNAs were found to differentially express in XX-DSD pigs compared with normal female pigs. Many genes in hormone biosynthesis and secretion pathway are signi cantly up-regulated, and the upregulation of GNRH1, KISS1 and AVP may be the candidate genes leading the abnormal secretion of GnRH. Next, we predicted the lncRNA-miRNA-mRNA co-expression triplets and constructed three competing endogenous RNA (ceRNA) potentially associated with DSD. Functional enrichment suggested TCONS_00340886, TCONS_00000204 and miR-181a were related to GnRH secretion.
ConclusionsOur research revealed the rst transcriptomic pro le in the hypothalamus of XX-DSD pigs and provided new insight in coding and non-coding RNAs that may be associated with DSD in pigs.