Gene expression signatures associated with chronic endometritis revealed by RNA sequencing

Abstract

IntroductionChronic 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.MethodsUsing 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.Results and DiscussionBy 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 MUC5AC, LTF, CAPN9, MESP1, ACSM1, TVP23A, ALOX15, and MZB1. 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: CCDC13 by comparing the samples in the proliferative phase, and OVGP1, MTUS2, and CLIC6 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, TVP23A was upregulated in the majority of CE cases regardless of the number of CD138-positive cells. The upregulation of TVP23A 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.

Unveiling the Role of Endometrial CD-138: A Comprehensive Review on Its Significance in Infertility and Early Pregnancy

“…Studies have revealed that CD-138+ cells, particularly in the proliferative-phase endometrium, may be an adverse indicator for pregnancy outcomes in in vitro fertilization (IVF) cycles. Elevated counts of CD-138+ cells in the endometrium have been linked to pregnancy failure and are proposed to possess a specific predictive value for pregnancy outcomes [ 15 , 16 ]. Moreover, CD-138 immunohistochemistry has been employed to enhance the diagnostic accuracy of CE.…”

“…Moreover, CD-138 immunohistochemistry has been employed to enhance the diagnostic accuracy of CE. Research indicates that the quantification of CD-138-positive cells can be a reliable method for CE detection, with a diagnostic criterion of five or more CD-138+ cells per high-power field (HPF) [ 4 , 8 , 9 , 15 ].…”