Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?

OBJECTIVE

To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility.

DESIGN

Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders.

SETTING

Infertility research department affiliated with a university hospital.

PATIENT(S): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II-IV endometriosis.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Genomewide gene expression and altered molecular functions in the endometrium of each uterine disorder.

RESULT(S): Using robust analysis methods, we identified statistically significantly altered endometrial functions in all the uterine disorders. Cell cycle alterations were shared among all the pathologies investigated. Endometriosis was characterized by the down-regulation of ciliary processes. Among the endometriosis, ADC, and RIF samples, mitochondrial dysfunction and protein degradation were shared dysregulated processes. In addition, RPL had the most distinct functional profile, and 95% of affected functions were down-regulated.

CONCLUSION(S): The most robust functions dysregulated in the endometrium of patients with uterine disorders across sample cohorts implicated an endometrial factor at the gene expression level. This shared endometrial factor affects endometrial receptivity processes.