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Investigating Cycle-to-Cycle Variation and the Impact of Endometrial Injury through Differential Gene Expression Analysis

ABSTRACT: This prospective study investigated whether endometrial gene expression changes across two consecutive menstrual cycles and whether prior endometrial injury alters molecular profiles during the mid-luteal phase. Twenty women underwent paired endometrial biopsies, and differential gene expression was analysed using a paired design, adjusting for cycle timing. While samples from the same individual showed slightly greater similarity than those from different individuals, no significant gene expression changes were observed after endometrial injury (p > 0.05), including in subgroup analyses of fertile and infertile participants. Principal component analysis showed no clear clustering by individual, further highlighting cycle-to-cycle variability. These findings suggest that intra-individual molecular variability is largely due to biological fluctuations rather than any lasting effect of endometrial injury. This may help explain inconsistent outcomes in implantation and limited utility of interventions like endometrial injury and molecular receptivity testing in IVF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303049 | GEO | 2026/05/15

REPOSITORIES: GEO

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Project description:The equine endometrium exhibits characteristic morphological and functional changes during the estrous cycle controlled by the interplay of progesterone and estradiol. A microarray analysis of endometrial tissue samples derived from 5 time points of the estrous cycle (D0, D3, D8, D12, and D16) was performed to study the dynamics of endometrial gene expression. Endometrial biopsies were collected from five mares (Bavarian Warmblood) at the respective time points. Samples were divided and subjected to isolation of RNA for microarray analysis and analysis of tissue composition. Blood samples were collected to determine serum progesterone levels for every sample. Statistical analysis of microarray data revealed almost 10,000 differential probes corresponding to 4,996 differentially expressed genes. A cluster analysis based on gene expression profiles during the estrous cycle revealed 8 major gene expression profiles: mRNAs with highest levels 1) at D0, 2) from D0 to D3, 3) at D3, 4) from D3 to D8, 5) at D8, 6) from D8 to D12, 7) from D12 to D16, and 8) at D16. DAVID Functional Annotation Clustering revealed overrepresentation of distinct functional terms in different phases of the cycle, e.g. M-bM-^@M-^Xextracellular matrixM-bM-^@M-^Y and M-bM-^@M-^Xprotein transportM-bM-^@M-^Y during estrus, M-bM-^@M-^XDNA replication and M-bM-^@M-^Xcell cycleM-bM-^@M-^Y during early luteal phase, M-bM-^@M-^Xendoplasmic reticulumM-bM-^@M-^Y and M-bM-^@M-^Xprotein transportM-bM-^@M-^Y in the luteal phase, and M-bM-^@M-^Xinflammatory responseM-bM-^@M-^Y in the late luteal and follicular phase. Expression of selected genes of the expression clusters was validated by quantitative Real-time PCR (qPCR). This study provides new insights into global changes of equine endometrial gene expression during the estrous cycle. Equine endometrial tissue samples were collected at 5 time points during the sexual (estrous) cycle from 5 mares (5 biological replicates per time point) and analyzed with Agilent microarrays.

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Investigating Cycle-to-Cycle Variation and the Impact of Endometrial Injury through Differential Gene Expression Analysis

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