What We Have Learned from Animal Models to Understand the Etiology and Pathology of Endometrioma-Related Infertility

Abstract

Endometrioma (OMA) is the most common subtype of endometriosis, in which the endometriotic lesions are implanted in the ovary. Women with OMA are usually associated with infertility, presenting with reduced ovarian reserve, low oocyte quantity and quality, and poor fertility outcomes. However, the underlying pathological mechanisms in OMA-related infertility are still unclear. Due to the limitations and ethical issues of human studies in reproduction, animal models that recapitulate OMA characteristics and its related infertility are critical for mechanistic studies and subsequent drug development, preclinical testing, and clinical trials. This review summarized the investigations of OMA-related infertility based on previous and latest endometrioma models, providing the possible pathogenesis and potential therapeutic targets for further studies.

Diminished Ovarian Reserve in Endometriosis: Insights from In Vitro, In Vivo, and Human Studies—A Systematic Review

“…As mentioned before, the perioperative inflammatory reactions could increase the level of inflammatory cytokines, which further decreases OR among women with endometriosis who have undergone laparoscopic cystectomy [117]. Additionally, from prior literature, it is mentioned that inflammation may induce excessive oxidative stress, which thereby leads to fibrosis of the ovarian cortex and further results in a reduction in OR and the DNA damage of oocytes during and after folliculogenesis [12,15,149]. Oxidative stress caused by excess reactive oxygen species (ROS) and the imbalance of antioxidants in the follicular microenvironment was regarded as important for inducing follicle senescence.…”

“…Out of the 21 studies included, 10 were conducted on humans, 11 were conducted on in vivo models, and among these studies, 4 continued their investigations using in vitro models. Peritoneal endometriosis is the most frequently studied subtype in in vivo models due to its standardized methodology, while endometrioma (OMA) is the most common subtype in clinics [12]. As endometriosis can have varying effects on OR and its underlying mechanisms depending on the subtype, it raises awareness that different subtypes of in vivo models should be applied to explore this topic thoroughly.…”

“…Endometriosis models range from non-human primates (NHPs) to rodents [12]. NHPs such as cynomolgus monkeys and baboons are widely applied as experimental animal models for endometriosis since they process cyclic menstruation, which enables the development of spontaneous endometriosis [128].…”

“…The review published by our team in 2022 concluded that endometriosis can remarkably impair the development of follicles and deteriorate the quality of oocytes by activating primordial follicles prematurely [12,168]. The role of the PI3K-PTEN-Akt-Foxo3 signaling pathway has been extensively studied over the years, revealing that PTEN inhibition acts as a major negative regulator of PI3K/AKT activity [16,169].…”