Circadian rhythm misalignment may increase risk for ovarian endometriosis in women
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Women with circadian rhythm misalignment may be at a greater risk for developing ovarian endometriosis, according to data presented at the European Congress of Endocrinology.
In a cohort of women with confirmed ovarian endometriosis, researchers observed altered messenger RNA (mRNA) expression of clock genes in ectopic tissues compared with eutopic samples, indicating a disturbance in circadian rhythm timing.
“Endometriosis affects roughly 10% of reproductive-age women and girls globally,” Eva Kassi, MD, PhD, a professor at the National and Kapodistrian University of Athens Medical School in Greece, told Healio. “In severe cases, it can be very painful and can cause infertility, miscarriages and ectopic pregnancies. The clinical observation that biological rhythm disturbances, as seen in night-shift workers, are associated with endometriosis is now molecularly confirmed by the altered expression of local circadian clock genes in ectopic endometrium compared to eutopic. Understanding the causes and effects of endometriosis will improve our ability to detect, manage or even prevent the condition.”
Researchers recruited 31 women with confirmed ovarian endometriosis for the study. In 11 participants, paired samples of ectopic endometrial tissues and eutopic tissues were collected. Ectopic and eutopic endometrial tissues were collected from 10 participants, and researchers collected normal endometrial tissue from 10 women with uterine fibroids. Researchers conducted real-time quantitative polymerase chain reaction tests to analyze CLOCK, BMAL1, CRY-1, PER-2, ROR-alpha and REV-ERBb gene expression in ectopic tissues compared with eutopic tissues.
In analysis of total ectopic tissue samples compared with total eutopic tissues, the mRNA expression of the PER-2 and CRY-1 genes was decreased in the ectopic tissue. There was a marginal reduction in expression of the CLOCK gene and a marginal increase in REV-ERBb gene expression in ectopic tissues compared with eutopic tissues.
The expression of PER-2 and CRY-1 genes was significantly lower in ectopic samples compared with paired eutopic tissues, whereas REV-ERBb expression were significantly higher in ectopic tissues compared with paired eutopic samples. There was also a marginal decrease in CLOCK gene expression in ectopic tissues vs. paired eutopic tissues.
Compared with ectopic tissues, expression of the REV-ERBb and BMAL1 genes was lower in normal samples.
Kassi said the findings show an altered expression of several clock genes in women with ovarian endometriosis, but do not confirm a causal relationship between altered gene expression and development of endometriosis.
“Mechanistic studies of silencing clock genes in normal endometrial cells will shed light on a possible causal role of the local circadian system in the pathogenesis of endometriosis, as either an initiating, predisposing or propagating factor,” Kassi said. “The causal role becomes more likely as core clock proteins regulate processes which are known to be involved in the immune-dysfunctions in the peritoneal niche and the endometriosis-associated infertility.”
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Nasiri-Ansari N, et al. Abstract #1394. Presented at: European Congress of Endocrinology; May 22-26, 2021 (virtual meeting).
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