Endocrine Abstracts

Introduction

Endometriosis is a dysplastic disease affecting approximately 7–10% of reproductive–aged women. It is defined as the presence of endometrial-like tissue outside the uterine cavity. Disruption of circadian rhythm in night shift worker has been associated with menstrual irregularity and increased chance of developing endometriosis and ovarian tumors. The central circadian clock system located in hypothalamic suprachiasmatic nucleus (SCN) along with the peripheral clock system located in the reproductive tissues (endometrium) control the timing and length of the ovulatory cycle by regulating the expression of various hormones ( i.e.gonadotropins, estradiol) which in turn regulate the expression of clock related genes and vise-versa. To best of our knowledge, no studies related to the alterations in expression profile of the core clock -genes in human endometriosis have been published to date.

Aim

Herein, we aimed to investigate the expression of the core clock related genes in paired eutopic and ectopic endometrial tissues.

Methods

27 patients with confirmed ovarian endometriosis were included in this study. 11 paired samples were collected from ovarian cysts (ectopic endometrial tissues) and normal endometrium (eutopic tissues) while further 8 ectopic and 8 eutopic endometrial tissues were collected from 16 different patients with the same diagnosis. The mRNA expression of Clock-genes (CLOCK, BMAL1, CRY-1, PER-2, ROR-α and REV-ERBb) was evaluated by qPCR in ectopic tissues and was compared with the eutopic tissues.

Results

The mRNA expression of PER-2 and CRY-1 genes was decreased in the total of ectopic tissues (n = 19) compared to the total eutopic tissues (n = 19) (P = 0.02, P = 0.02 respectively). A marginal reduction in the expression of CLOCK along with a marginal increase in REV-ERBb expression was noted (P = 0.06 and P = 0.09 respectively) in ectopic (n = 19) compared to eutopic tissues (n = 19). The mRNA expression of clock-genes in the ectopic (n = 11) compared to their paired eutopic tissues (n = 11) revealed that the expression of PER-2 and CRY-1 genes were significantly lower (P = 0.04, P = 0.04, respectively), whereas REV-ERBb levels was significantly elevated (P = 0.02). Additionally, a marginal decrease in the expression of clock gene in ectopic as compared to paired eutopic tissues was observed (P = 0.09). Of note, the mRNA levels of BMAL1 and ROR-α were not altered between our studied groups.

Conclusions

Our study demonstrates for the first time an altered expression of CLOCK, CRY1, PER-2, and Rev-ERBb in eutopic as compared to ectopic endometrial tissues indicating circadian clock disruption. However, the causal relationship of the altered expression pattern of these genes with the development of endometriosis needs further investigation.