Kisspeptin and its Receptor in the Pathogenesis of Endometriosis

Kisspeptin downregulation may play a role in endometriosis pathogenesis and progression.

Key Points

Highlights:

• Low Kisspeptin (KISS1) in ectopic endometrial tissue may allow continued tissue invasion, resulting in deep ectopic implants and cyst formation.

Importance:

• The dissemination and invasion of endometriotic implants may be reduced by kisspeptin analogs.

What’s done here?

• The authors investigated the immunoreactivity of KISS1 and its receptor in the eutopic endometrium of patients with and without endometriosis, in different menstrual cycle phases and in the three types of endometriotic lesions: superficial lesions from peritoneal endometriosis, deep infiltrating endometriosis, or endometriotic ovarian cysts also known as endometriomas.
• Endometrial samples from 14 reproductive-aged women without endometriosis and endometriosis samples from 35 patients were included in the study.

Key Points:

• KISS1 and KISS1R immunoreactivity between proliferative and secretory phases in the eutopic endometrium of women without endometriosis was not found to be significantly different.
• KISS1 immunoreactivity and KISS1R levels were significantly lower for both glandular and stromal components of the eutopic endometrium from women with endometriosis than without endometriosis.
• In endometriotic tissues, KISS1 immunoreactivity was found to be significantly lower in glandular and stromal cells of deep infiltrating endometriosis and endometriomas compared to those of peritoneal superficial lesions.

Limitations:

• This study is retrospective and based on archive specimens, and does not include samples from adolescents, in whom the pathogenesis of endometriosis may differ.

Lay Summary

It is known that matrix metalloproteinases (MMP) may play a role in the pathogenesis of endometriosis. For example, the upregulation of MMP-2 and MMP-9 may enhance the degradation of extracellular matrix proteins, facilitating cell migration and invasion. Kisspeptin (KISS1, also known as metastin), a neuropeptide hormone, encoded by the KISS1 gene, may interact with MMPs in endometrial tissue.

Abdelkareem et al. evaluated the immunoreactivity of KISS1 and its receptor in the eutopic endometrium of patients with and without endometriosis, in different menstrual cycle phases and in the three types of endometriotic lesions: superficial lesions from peritoneal endometriosis, deep infiltrating endometriosis, or ovarian endometriotic cysts also known as endometriomas. The article is published online in the February 2020 issue of "Reproductive Sciences".

The study is carried out on endometrial samples from 14 reproductive-aged women without endometriosis and endometriosis samples from 35 patients. Ectopic lesions from only one lesion type were obtained from each patient, except three patients who provided both deep infiltrating endometriosis and endometriomas. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on these samples. Immunoreactivity was quantified using histoscores.

No significant difference was found in KISS1 and KISS1R immunoreactivity between proliferative and secretory phases in the eutopic endometrium of women without endometriosis. KISS1 immunoreactivity and KISS1R levels were significantly lower for both glandular and stromal components eutopic endometrium of women with endometriosis than without endometriosis. The authors stated that this is consistent with the hypothesis that lower KISS1/KISS1R expression contributes to the pathogenesis of endometriosis by promoting tissue invasion. They also suggested that decreased KISS1 signaling may relieve suppression of MMP-2 and MMP-9, thereby allowing increased extracellular matrix degradation.

In endometriotic samples, KISS1 immunoreactivity was found to be significantly lower in glandular and stromal cells of the deep infiltrating endometriosis and endometriomas compared to those of peritoneal superficial lesions. Based on these findings, the authors postulated that continued low KISS1 in ectopic endometrial tissue may allow continued tissue invasion, resulting in deep ectopic implants and cyst formation.

In conclusion, the researchers suggested that kisspeptin downregulation may play a role in endometriosis pathogenesis and progression. They also indicated that kisspeptin analogs may have the potential to reduce the dissemination and invasion of endometriotic implants. 

Research Source: https://pubmed.ncbi.nlm.nih.gov/32072605