AUTHOR=Oshina Kyoko , Kuroda Keiji , Nakabayashi Kazuhiko , Tomikawa Junko , Kitade Mari , Sugiyama Rikikazu , Hata Kenichiro , Itakura Atsuo 

TITLE=Gene expression signatures associated with chronic endometritis revealed by RNA sequencing

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1185284

DOI=10.3389/fmed.2023.1185284

ISSN=2296-858X

ABSTRACT=<sec><title>Introduction</title><p>Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium characterized by the infiltration of plasma cells in the endometrial stroma. CD138 immunohistochemistry is considered to improve the CE diagnosis rate.</p></sec><sec><title>Methods</title><p>Using the number of CD138-positive cells equal or greater than five as a diagnostic criterion for CE, we identified 24 CE and 33 non-CE cases among women with infertility. We conducted RNA-sequencing analysis for these 57 cases in total as an attempt to elucidate the molecular pathogenesis of CE and to search for new biomarkers for CE.</p></sec><sec><title>Results and Discussion</title><p>By comparing CE and non-CE groups, we identified 20 genes upregulated in the endometria of CE patients, including 12 immunoglobulin-related genes and eight non-immunoglobulin genes as differentially expressed genes. The eight genes were <italic>MUC5AC</italic>, <italic>LTF</italic>, <italic>CAPN9</italic>, <italic>MESP1</italic>, <italic>ACSM1</italic>, <italic>TVP23A</italic>, <italic>ALOX15</italic>, and <italic>MZB1</italic>. By analyzing samples in the proliferative and secretory phases of the menstrual cycle separately, we also identified four additional non-immunoglobulin genes upregulated in CE endometria: <italic>CCDC13</italic> by comparing the samples in the proliferative phase, and <italic>OVGP1</italic>, <italic>MTUS2</italic>, and <italic>CLIC6</italic> by comparing the samples in the secretory phase. Although the genes upregulated in CE may serve as novel diagnostic markers of CE, many of them were upregulated only in a limited number of CE cases showing an extremely high number of CD138-positive cells near or over one hundred. Exceptionally, <italic>TVP23A</italic> was upregulated in the majority of CE cases regardless of the number of <italic>CD138</italic>-positive cells. The upregulation of <italic>TVP23A</italic> in the endometria of CE cases may reflect the pathophysiology of a cell-type or cell-types intrinsic to the endometrium rather than the accumulation of plasma cells. Our data, consisting of clinical and transcriptomic information for CE and non-CE cases, helped us identify gene expression signatures associated with CE.</p></sec>