ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Early Pregnancy with Subclinical Hypothyroidism.

Subclinical hypothyroidism (SCH) is associated with multiple adverse outcomes in early pregnancy. This study aims to explore the regulatory mechanisms underlying histone lactylation modification in early pregnancy with SCH. Peripheral blood mononuclear cells were collected from early pregnant women with or without SCH. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses were performed to identify the transcriptional pattern and histone lactylation modification in early pregnancy with SCH. RNA-seq analysis revealed that the differentially expressed genes associated with the extracellular matrix exhibited a significant downregulation in early pregnancy with SCH (EP_SCH) compared to early pregnancy without SCH (EP), while those involved in apoptosis were significantly upregulated. In the ChIP-seq analysis, 1660 hypomodified and 766 hypermodified H3K18la-binding peaks were identified in the EP_SCH group compared to the EP group. The hypomodified genes in early pregnancy with SCH compared to its control were enriched in GO terms of apoptotic process and differentiation of immune cells. The genes with increased H3K18 lactylation in early pregnancy with SCH compared to its control were associated with the nervous system, female pregnancy, and the OXT signaling pathway. When RNA-seq data was integrated with ChIP-seq data, we found that the expression and H3K18la enrichment of KCTD7, SIPA1L2, HDAC9, BCL2L14, TXNRD1, and SGK1 were increased in early pregnancy with SCH compared to its control, which was further confirmed by RT-qPCR and ChIP-PCR analyses. This study identifies the changes in histone lactylation modification in early pregnancy with SCH. These findings provide novel insights into the regulatory mechanisms of SCH during early pregnancy.