INTRODUCTION: Diabetes mellitus (DM) and associated comorbidities correspond to female infertility by many interrelated mechanisms. Yet most prior research focuses only on ovary dysfunction. Our work evaluates literature mechanisms of DM-induced uterine tube and endometrial dysfunction, corresponding impacts on female fertility, and potential evidence-based intervention targets. METHODS: We conducted a scoping review (mapping review) follows the Joanna Briggs Institute (Manual for Evidence Synthesis, 2020 version). After identifying the research questions, we conducted a comprehensive search across four electronic databases by entering the keyword "diabetes", with a combination with other keywords as the uterus, endometrium, uterine/Fallopian tube, infertility and embryo implantation. We excluded manuscripts that address the issue of gestational diabetes. Most of these studies were in animals. RESULTS: There is compelling evidence for connecting DM with uterine tube infertility via endometriosis, thyroid dysfunction, and susceptibility to infectious disease. DM damages the endometrium before pregnancy via glucose toxicity, lesions, excessive immune activity, and other mechanisms. DM also hinders endometrium receptivity and embryo-endometrium crosstalk, such as through disrupted endometrium glucose homeostasis. We also hypothesize how DM may affect the function of immune cells in uterine tube and uterus, including changes in the number and types of cells of innate and acquired immunity, disrupting immunological barrier in uterine tube, alterations in formation of neutrophil extracellular traps or polarization of macrophages. DISCUSSION: We discuss evidence for clinical practice in terms of glycaemic control, lifestyle modifications, and medical interventions. For example, there is currently substantial evidence from rodent models for using metformin for increase in endometrial thickness, number of stromal cells and blood vessels and restoration of normal endometrial architecture, and bariatric surgery for recruitment of protective immune cell types to the endometrium. We also briefly highlight the future prospects of stem cells, artificial intelligence, and other new approaches for managing DM-associated female infertility. Further studies are necessary for optimizing female reproductive outcomes.

• Keywords
• diabetes mellitus, embryo-endometrium crosstalk, endometrial immune cell, endometrial receptivity, hyperglycaemia, hypothyroidism, infertility, tubal infertility,
• Publication type
• Journal Article MeSH
• Review MeSH

The uterine tube, as well as other parts of the upper female reproductive system, is immunologically unique in its requirements for tolerance to allogenic sperm and semi-allogenic embryos, yet responds to an array of sexually transmitted pathogens. To understand this dichotomy, there is a need to understand the functional morphology of immune cells in the wall of the uterine tube. Thus, we reviewed scientific literature regarding immune cells and the human uterine tube by using the scientific databases. The human uterine tube has a diverse population of immunocompetent cells representing both the innate and adaptive immune systems. We describe in detail the possible roles of cells of the mononuclear phagocyte system (macrophages and dendritic cells), T and B lymphocytes, natural killer cells, neutrophils and mast cells in association with the reproductive functions of uterine tubes. We are also discussing about the possible "immune privilege" of the uterine tube, as another mechanism to tolerate sperm and embryo without eliciting an inflammatory immune response. In uterine tube is not present an anatomical blood-tissue barrier between antigens and circulation. However, the immune cells of the uterine tube probably represent a type of "immunological barrier," which probably includes the uterine tube among the immunologically privileged organs. Understanding how immune cells in the female reproductive tract play roles in reproduction is essential to understand not only the mechanisms of gamete transport and fertilization as well as embryo transport through the uterine tube, but also in improving results from assisted reproduction.

• Keywords
• B lymphocyte, T lymphocyte, dendritic cell, fertility, macrophage, mast cell, natural killer cell, uterine tube,
• Publication type
• Journal Article MeSH
• Review MeSH

The uterine tube (UT) pathologies account for 25-35% of female factor infertility. Although these peculiar organs were first studied several hundred years ago, they have become overlooked and neglected mainly due to the successes of reproductive medicine. Nevertheless, the reproductive medicine still faces many challenges regarding the fertility outcomes of in vitro fertilization (IVF). Many obstacles and problems can be resolved by a more detailed understanding of the UT morphology and function during normal reproduction. Over the course of the 21st century, many new insights have been obtained: the presence of a population of telocytes in the tubal wall responsible for normal motility and hormone sensory function, the demonstration of lymphatic lacunae of the mucosal folds necessary for oocyte capture and tubal fluid recirculation, or a thorough profiling of the immune makeup of the UT epithelial lining with the discovery of regulatory T cells presumably important for maternal tolerance towards the semi-allogenic embryo. New discoveries also include the notion that the UT epithelium is male sex hormone-sensitive, and that the UT is not sterile, but harbors a complex microbiome. The UT epithelial cells were also shown to be the cells-of-origin of high-grade serous ovarian carcinomas. Finally, yet importantly, several modern morphological directions have been emerging recently, including cell culture, development of tubal organoids, in silico modelling, tissue engineering and regenerative medicine. All these novel insights and new approaches can contribute to better clinical practice and successful pregnancy outcomes.

• MeSH
• Epithelium MeSH
• Fertility * MeSH
• Fertilization in Vitro MeSH
• Humans MeSH
• Ovary MeSH
• Pregnancy MeSH
• Fallopian Tubes * pathology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH