| چکیده انگلیسی مقاله |
Endometriosis, a complex gynecological disorder characterized by ectopic endometrial-like tissue, affects over 10% of women, causing chronic pain and infertility. Despite extensive research, its pathophysiology remains incompletely understood, with proposed mechanisms including inflammation, hormonal dysregulation, and retrograde menstruation. Given ethical and practical challenges in human studies, animal models are essential for investigating endometriosis pathogenesis and evaluating therapeutic interventions. This review examines hormone-related animal models of endometriosis, comparing induction methods (autotransplantation, xenotransplantation, and spontaneous models) and their applications in studying sex steroid hormones (SSH) and the hypothalamic-pituitary-gonadal (HPG) axis. We analyzed 158 studies (2010–2024) from PubMed Central/Medline, focusing on SSH and HPG axis involvement. A novel scoring system was developed to assess the model’s suitability based on species, induction method, pharmacological effects, hormonal/genetic evaluations, histological confirmation, feasibility, ethics, and cost. Non-human primate models, particularly spontaneous and hormone-induced baboon models, scored highest due to their physiological resemblance to humans. However, rodent models remain widely used due to practicality. Our findings highlight the need for improved preclinical models to enhance translational research, ultimately aiding in the development of targeted therapies for endometriosis. This comprehensive analysis provides a framework for selecting optimal animal models in future endometriosis research. |
| کلیدواژههای انگلیسی مقاله |
Sex steroid hormones, Estrogens, Progesterone, Endometriosis, Models, animal, What&,rsquo s Known Endometriosis is a hormone-dependent gynecological disorder characterized by ectopic endometrial-like tissue growth, often studied using animal models to explore its pathogenesis and treatment. Previous research has established the role of sex steroid hormones and the hypothalamic-pituitary-gonadal axis in endometriosis progression, with various animal models employed to mimic the disease. What&,rsquo s New Our comprehensive analysis highlights key improvements in model selection, emphasizing hormonal and genetic consistency with human endometriosis, thereby enhancing the reliability of preclinical studies for therapeutic development. This study introduces a novel scoring system to evaluate hormone-related endometriosis animal models, identifying the &,ldquo unopposed estrogenicity model in baboons&,rdquo as the most effective for translational research. IntroductionEndometriosis is a non-cancerous condition characterized by the growth of tissue resembling the endometrium in areas outside the uterine cavity. It commonly leads to symptoms such as ongoing pelvic discomfort, pain associated with the menstrual cycle, and difficulties with fertility. It is estimated that over 10% of women are affected by this condition. 1, , 2, While various mechanisms of endometriosis generation have been thoroughly studied, the processes leading to its development and maintenance are not yet completely understood, and significant gaps in research remain. The development of new surgical methods and medications for the prevention and elimination of disease or its recurrence necessitates defining the pathophysiologic mechanisms.Endometriosis is a multifactorial disease, and various models and approaches have been proposed to explain its pathophysiology. 3, Widely accepted pathophysiological aspects can be classified as inflammation, 4, immunological factors, 5, environmental factors, 6, genetics, 7, pain, 8, infertility, 9, and hormonal. While several theories are described in each category, it is not certain which one is the primary reason for the occurrence of endometriosis. Still, one of the main theories for the ectopic formation of endometrial tissue in the peritoneal cavity is considered to be the old &,ldquo retrograde menstruation&,rdquo . 10, Retrograde menstruation, a theory proposed over 100 years ago, suggests that menstrual blood flows backward through the fallopian tubes into the pelvic cavity. 11, While this theory has historical significance, it is important to note that more recent research has proposed alternative mechanisms for the development of endometriosis, including the stem cell origin theory. 12, This newer theory suggests that stem cells from the bone marrow or endometrial tissue itself may contribute to the formation of endometriotic lesions. 13, Estrogen-dependency of endometriosis has been well documented, 14, and drugs that reduce or suppress sex steroid production in ovaries for endometriosis treatment 15, or relief of its symptoms, such as pain, 16, have been proposed. One of the key modulators in endometriosis pathogenesis is the increasing local production of estrogens. 17, Many effects of sex steroids are mediated by their actions at their nuclear receptors, but growing evidence suggests that some effects may occur independently of these receptors. 18, Due to the delay in diagnosing the disease and its progression by the time it is diagnosed, conducting experiments to detect predisposing factors related to synthesis or involved in sex steroid effects in endometriosis is not feasible. Due to ethical considerations, controlled experiments such as disease progression monitoring by repeated laparoscopies are limited. Therefore, animal models of endometriosis can be valuable for conducting extensive research on the effects of sex steroids and their mechanisms, including ectopic endometrial tissue adherence, invasion, and vascular establishment. They also facilitate the development of new approaches to study the initial onset, recurrence prevention, and the treatment of lesions.The closest models to humans for evaluating endometriosis have been non-human primates. However, their use raises serious ethical concerns due to their high cognitive abilities, social structures, and the challenges associated with their care and handling. Due to their high cost and handling limitations, small laboratory animals have been used as alternative models of endometriosis. This literature review aims to provide comprehensive insight into hormone-related animal models of endometriosis and compare different induction methods, along with their advantages, disadvantages, and applications for evaluating sex steroid hormones (SSH) in the pathogenesis of endometriosis. Additionally, a summary of all published studies is provided, and a novel scoring table is designed to provide a full understanding of the most important aspects of available animal models.We used PubMed Central/Medline databases to find research on sex hormone-related endometriosis. All included studies were published between 2010 and 2024. The Mendeley Desktop application 1.19.8 (Mendeley Ltd., London, UK) was used to screen the results. The following search query was utilized to discover all related papers, resulting in 158 related papers within our desired time interval, &,ldquo endometriosis&,rdquo [Title/Abstract] AND (&,ldquo animal&,rdquo [Title/Abstract] OR &,ldquo model&,rdquo [Title/Abstract]) AND (&,ldquo hormone&,rdquo [Title/Abstract] OR &,ldquo sex&,rdquo [Title/Abstract] OR &,ldquo steroid&,rdquo [Title/Abstract]). We included studies published between 2010 and early 2024 that proposed an endometriosis induction method in animals as the first criterion. An assessment of SSH or hypothalamic-pituitary-gonadal (HPG) axis hormones (receptors or concentration assessment) was the second inclusion criterion. We summarized all the studies that met our inclusion criteria in table 1,, and articles that represented a novel induction method were classified separately. The more traditional and widely used approaches in these studies were also reviewed and explained separately.Animal modelsAuthor, year, Reference Author, year, Source of utilized methodEstrogen and its receptors&,rsquo role in endometriosis |
| نویسندگان مقاله |
Amin Tamadon |
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Afshin Zare |
PerciaVista R&D Co., Shiraz, Iran
Mahdi Mahdipour |
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Aria Salehpour |
PerciaVista R&D Co., Shiraz, Iran
Nadiar M. Mussin |
Department of General Surgery, West Kazakhstan Medical University, Aktobe, Kazakhstan
Aliya A. Mussina |
Department of Family Medicine No 1, Astana Medical University, Astana, Kazakhstan
Raisa A. Aringazina |
Department of Internal Medicine No. 1, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Ainash Duisenova |
Department of Psychology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Republic of Kazakhstan
Kulyash R. Zhilisbayeva |
Department of Languages, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Madina A. Kurmanalina |
Department of Therapeutic and Prosthetic Dentistry, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Chong Fu |
Health Management Center, The Fifth People's Hospital of Chongqing,Chongqing,400060, China
|