Glycodelin and altered endometrial function in endometriosis

Dysregulation of Glycodelin in Endometriosis may be the Cause of Fertility Problems

Key Points

Highlight:

• Glycodelin (GdA) is a complex glycoprotein that specifically expressed during the different phases of menstrual cycle.
• GdA is altered in endometriosis, and this possibly relates to the impaired endometrial receptivity.

Importance: 

• GdA is a potential biomarker of endometrial function that may one day be useful for non-invasive diagnosis of endometriosis.

What's done here:

• Expression profiling of GdA and its glycosylation were examined in endometrial tissues from women with endometriosis and women with fertility, at different times during the menstrual cycle.
• A total of 22 endometrial specimens were collected by hysteroscopy from:
  • fertile women undergoing laparoscopy for tubal sterilization and
  • Twenty infertile women affected by endometriosis undergoing laparoscopic surgery.

Data:

• GdA expression changed during the normal menstrual cycle.
• The profile of GdA glycosylated glycoforms was differentially expressed in each phase of the menstrual cycle comparing endometrium from endometriosis and fertile women.
• Specifically, eutopic endometrium of endometriosis patients showed a significant increase in GdA protein expression and different glycoforms during the secretory phase.
• GdA protein localization was observably different in healthy endometrium compared to the endometriotic endometrium.

Limitations:

• Small sample size.
• Functional consequences of altered GdA in endometrium are not clear.
• This may be just an association rather than a casual relationship, or there may be other factors affecting GdA alterations.

Lay Summary

A laparoscopic examination is the only diagnostic tool for endometriosis to date. Since the procedure is invasive, there has been much effort by researchers to develop a biomarker for non-invasive diagnosis of endometriosis. To this end, there has been growing interest in studies on GdA, which was formerly known as "placental protein 14" as a candidate biomarker. However, little is known about its expression in the endometrium during the menstrual cycle and in endometriosis. GdA is a glycoprotein with several biological functions including immunosuppression which can undergo glycosylation that may markedly alter its function.

In the study by Focarelli et al. from the University of Siena, Siena, Italy, reported in Reproductive Sciences. The researchers aimed to assess the expression of GdA and its different glycosylated forms by several molecular biology techniques to understand whether GdA expression changes in endometrium during the menstrual cycle and also in eutopic endometrium of patients with endometriosis. Endometrial specimens collected from 22 fertile women as control, and 20 infertile women affected by endometriosis.  

The results showed that GdA expression could change during the normal menstrual cycle. The profile of GdA glycosylated glycoforms differentially expressed in each phase of the menstrual cycle in endometriotic eutopic endometrium which showed a significant increase in GdA protein expression and different glycoforms during the secretory phase. Furthermore, GdA protein localization was observably different in healthy endometrium compared to the endometriotic endometrium. The secretory phase of the menstrual cycle occurs after ovulation when the corpus luteum secretes progesterone to prepare the endometrium for the implantation of an embryo. Thus, it is possible that the altered expression of GdA may relate to progesterone failure and impacts on the proper endometrial function during the menstrual cycle, and may also account for the fertility problems associated with endometriosis.

Although GdA and its glycoforms were found to be altered, their pathogenic consequences have not been studied. The potential use of the GdA glycoforms as a biomarker was also not explored. Future studies to evaluate these aspects regarding GdA will be required. This study showed alteration of GdA during the menstrual cycle and in endometriosis, and the data supported previous observation that GdA is a biochemical marker of endometrial function.

"Our results of elevated GdA expression and its differential presence of its glycoforms in the eutopic endometrium during the late secretory phase may account for the fertility problems diagnosed in endometriotic women, suggesting that these endometrial abnormalities may create an unreceptive endometrial environment" concluded authors.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28683601