Autophagy may contribute to endometriosis and uterine fibroids

Autophagy is a controlled lysosomal degradation pathway that protects cells and allows to overcome cell death.

A review in the journal Fertility &Sterility Reviews has outlined emerging evidence that autophagy may contribute to the onset of endometriosis and uterine fibroids.1

Autophagy is a controlled lysosomal degradation pathway that protects cells and allows to overcome cell death.

In the uterus, autophagy is deregulated in both endometriosis and uterine fibroids. This common element may be 1 of the factors involved in the complex pathogenesis of both pathologies.

“It is well known that endometriosis and uterine fibroids are extremely common worldwide, though often underdiagnosed, and represent a serious burden for the public health system,” said senior author Paola Marcolongo, PhD, an assistant professor of pathology at the University of Siena in Italy. “Many women do not respond to pharmacological treatments and need surgery, highlighting the need for new therapeutic options to improve significantly the quality of life and preserve fertility.”

The PubMed review was inspired by the increasing number of scientific papers addressing autophagy and its role in reproduction, plus the emerging evidence showing that deregulated autophagy potentially promotes the onset of endometriosis and uterine fibroids.

“Autophagy is a controlled lysosomal degradation pathway by which self-components of the cell are broken down, thus contributing to cell survival,” Marcolongotold Contemporary OB/GYN®. “This pathway is normally activated by nutrient deprivation and cell stress; however, an excessive autophagy can also lead to cell death.”

The pathophysiology of endometriosis and uterine fibroids

remains unclear, though numerous risk factors have been identified, including genetic predisposition, hormones, and proinflammatory cytokines.

Many recent scientific papers demonstrate a close link between autophagy and inflammation. In many clinical settings, autophagy appears to limit inflammation, whereas impairment of autophagy is connected to severe chronic inflammatory diseases like inflammatory bowel disease.

The role of autophagy can also certainly be dual–pro-survival or pro-death—according to Marcolongo. “Studies on endometriosis report contrasting results on the regulation of autophagy, whereas this process is definitely downregulated in uterine fibroids,” she said.

Contradictory results on involvement of autophagy in the pathogenesis of endometriosis might be due to individual studies analyzing samples from various anatomical sites and with different severity scores, according to the American Society of Reproductive Medicine.

“Therefore, these heterogeneous anatomical and clinical conditions can make the ambiguous role of autophagy even more apparent in dissimilar settings,” Marcolongo said.

The scientific literature reporting of a defective regulation of the autophagic process, Maracolongo said, “is extremely relevant from a clinical point of view because we can envision that the pharmacological modulation of the autophagic process could help clinicians slow down and limit the evolution of endometriosis and uterine fibroids, thereby improving fertility, with obvious physical and psychological benefits for the affected women.”

Future studies are needed to fully define the role of autophagy, which will likely lead to effective new pharmacological treatments for endometriosis and uterine fibroids acting on autophagy dysregulation.

“It is reasonable to expect that a fine-tuning of the autophagy could effectively limit the evolution of these two diseases and improve fertility,” Marcolongo said.

Reference

  1. Marcolongo P, Maellaro E, Luisi S. Regulation of autophagy in the uterus: from physiological processes to endometriosis and uterine fibroids. F&S Reviews. 2021. doi.org/10.1016/j.xfnr.2021.11.003