Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium

Abstract

As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17β-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients.

Association between Pre-Pregnancy Overweightness/Obesity and Pregnancy Outcomes in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

“…Oróstica et al found that similar tumor necrosis factor alpha (TNF-α) serum levels but higher TNF-α signaling with NFκB in endometrium of higher BMI range of PCOS women [ 51 ]. Xue et al further provided a theoretical basis of abnormal endometrium in PCOS women to explain the subfertility of women with PCOS, including anovulation-induced endometrial hyperplasia, hyper-androgenic inhibition of the growth, differentiation and decidualization of the endometrium, IR related disruption of glucose metabolism in the endometrial with subsequent impairment of endometrial receptivity, progesterone resistance of the endometrium and chronic inflammatory change producing a vicious circle that disrupts the physiological endocrine and metabolic microenvironment of the endometrial and affects the receptivity of the endometrium [ 52 ]. Furthermore, obesity is associated with impaired ovarian function, poor oocyte quality and decreased reproductive performance by elevated proinflammatory cytokines, such as interleukin 6 (IL-6) and TNFα as well as oxidative stress [ 53 , 54 ].…”

The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome

“…Interestingly, we observed an increase in the expression of the HOXA10 gene in the patients subjected to metformin and dietary intervention ( Figure 3 A). These results highlight the potential benefit of the intervention used in the present study on PCOS patients, since the HOXA10 gene is fundamental for the differentiation and receptivity of the endometrium [ 39 ]. The future assessment of gene expression (and DNA methylation) of endometrial receptivity markers such as CDH6 (cadherin 6), L-selectin ligands, osteopontin and its receptor αvβ3 integrin, and LIF is necessary to provide more information about the association among PCOS pathogenesis, endometrium receptivity, and the metformin and carbohydrate-controlled diet used in the present study [ 52 , 53 , 54 , 55 ].…”

“…To date, the PCOS etiology remains unclear. It has been established that the endometrium is a reproductive tissue affected by PCOS partly by alterations in gene expression [ 39 ] that in turn are associated with epigenetic changes. Lifestyle intervention and metformin therapy exert positive metabolic and endocrine effects on women with PCOS and tissues affected by the disease, such as the endometrium [ 40 ].…”

Cannabinoids and PPAR Ligands: The Future in Treatment of Polycystic Ovary Syndrome Women with Obesity and Reduced Fertility

“…In women with PCOS, many factors such as inflammation, metabolic disturbance, hormonal imbalance, and anovulation can disrupt the endometrium. This can result in endometrial hyperplasia and complications during pregnancy in the case of successful conception [ 60 ]. PCOS influences the long-term health risks in women at the reproductive and postreproductive stages of life also through metabolic effects [ 61 ].…”