- Metabolic Alterations of Uterine Grafts after extended Cold Ischemic Storage: Experimental Study in ewes. [Journal Article]
- MHMol Hum Reprod 2019 Jul 19
- Uterine transplantation from a deceased donor could become an available option for widely treating uterine infertility. However, this procedure requires more precise knowledge about the graft's toler…
Uterine transplantation from a deceased donor could become an available option for widely treating uterine infertility. However, this procedure requires more precise knowledge about the graft's tolerance to extended cold ischemia. Here, we sought to assess the uterine metabolic alterations after extended cold ischemic storage in a model of auto-transplantation in ewe. Fourteen uterine auto-transplantations were performed divided into 2 groups: 7 after 3 hours of cold ischemia time (CIT), 7 after 24 hours. Venous uterine blood was collected before uterus retrieval and during reperfusion (30, 60 and 90 min), thereafter, blood gases, lactate, glucose and amino-acids were analyzed. Apoptosis analyses were performed before uterus retrieval and following reperfusion in uterus biopsies. Twelve uterine auto-transplantations were successfully performed and 7 ewes were alive ≥8 days after transplantation. After reperfusion, a decrease in pH, a rise of lactate and lactate/glucose ratio, and a delayed decrease of pO2 were found in the 3 h CIT group. No significant variation of these parameters was observed in the 24 h CIT group. Significant decreases of amino-acids were observed during reperfusion and these decreases were more pronounced and concerned a larger number of compounds in the 24 h CIT group than in the 3 h CIT group. There was no significant uterine apoptotic signal in either group. Overall, these results suggest that extended CIT storage delayed restoration of aerobic glycolysis and induced an increase in amino-acid requirements of the uterus after reperfusion. However, this biochemical alteration did not reduce success rate for uterine transplantation.
- The estrogen-regulated lncRNA H19/miR-216a-5p axis alters stromal cell invasion and migration via ACTA2 in endometriosis. [Journal Article]
- MHMol Hum Reprod 2019 Jul 19
- Fibrotic tissue may contribute to the origin of some endometriosis-related symptoms, such as chronic pelvic pain and infertility. Alterations in the H19/miR-216a-5p/ACTA2 pathway may mediate the regu…
Fibrotic tissue may contribute to the origin of some endometriosis-related symptoms, such as chronic pelvic pain and infertility. Alterations in the H19/miR-216a-5p/ACTA2 pathway may mediate the regulation of eutopic endometrial stromal cell (euESC) invasion and migration and may represent a potential mechanism underlying fibrous tissue formation or fibrosis in women with endometriosis. In this study, we aimed to determine the expression of H19 and ACTA2 in endometrial tissues of women with endometriosis. Two groups of 23 infertile women with endometriosis and 23 matched infertile women without endometriosis were investigated. Primary cultured cells of endometrial tissues were analysed using RT-PCR and western blotting (WB) to determine expression of H19 and ACTA2. EdU, CCK8, and Transwell assays were used to study the functions of H19 and ACTA2. HEK 293 cells were used for luciferase assays to study miR-216a-5p binding sites with H19 and ACTA2. We found that H19 and ACTA2 levels were significantly higher in endometriosis euESCs than in control euESCs (P < 0.05) and were positively correlated in endometriosis euESCs. Luciferase assays indicated that H19 regulates ACTA2 expression via competition for inhibitory miR-216a-5p binding sites. Our results indicate that alterations in the estrogen/H19/miR-216a-5p/ACTA2 pathway regulated endometriosis euESC invasion and migration. Downregulation of H19 or ACTA2 inhibited endometriosis euESC invasion and migration, however estrogen promoted endometriosis euESC invasion and migration via H19. The main limitation of our study was that experiments were conducted in vitro and further in-vivo studies are required in the future. However, our study showed that primary cultured cells represented endometriosis cells more clearly than cell lines.
- Emerging roles of exosomal miRNAs in breast cancer drug resistance. [Journal Article]
- ILIUBMB Life 2019 Jul 19
- Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge …
Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients.
- Ferredoxin 1b deficiency leads to testis disorganization, impaired spermatogenesis and feminization in zebrafish. [Journal Article]
- EEndocrinology 2019 Jul 19
- The roles of steroids in zebrafish sex differentiation, gonadal development and function of the adult gonad are poorly understood. Herein, we have employed a ferredoxin 1b (fdx1b) mutant zebrafish to…
The roles of steroids in zebrafish sex differentiation, gonadal development and function of the adult gonad are poorly understood. Herein, we have employed a ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b-/- zebrafish mutants develop into viable adults, in which concentrations of androgens and the glucocorticoid, cortisol, are significantly reduced. Adult fdx1b-/- mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b-/- mutant zebrafish do not exhibit characteristic breeding behaviors, and sperm production is reduced, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b-/- mutant males by IVF. The testes of fdx1b-/- mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several pro-male and spermatogenic genes is decreased in the testes of fdx1b-/- mutant males, including pro-male transcription factor SRY-box 9a (sox9a) and spermatogenic genes insulin-like growth factor 3 (igf3) and insulin-like 3 (insl3). This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the impacts of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates.
- Endometrial biopsy and density of nerve fibers in eutopic endometrium. Looking for easier ways to diagnose endometriosis. [Journal Article]
- GEGynecol Endocrinol 2019 Jul 19; :1-4
- The purpose of study was to evaluate if there is any difference between nerve fibers density in eutopic endometrium in women with and without endometriosis. The prospective case - control study condu…
The purpose of study was to evaluate if there is any difference between nerve fibers density in eutopic endometrium in women with and without endometriosis. The prospective case - control study conducted between October 2013 and December 2015. The study included 60 reproductive age women undergoing laparoscopy for suspected endometriosis, pelvic pain, or infertility and not currently receiving hormonal treatment for at least 3 months prior to laparoscopy. Immunohistochemical nerve fiber detection in endometrial curetting using anti-gene product 9.5 was compared with surgical diagnosis. The nerve fibers were detected in eutopic endometrium in women with and without endometriosis. PGP9.5 positive nerve fibers were found in 26 (43%) cases: 16 (50%) in women with endometriosis and 10 (36%) in women without endometriosis. The mean nerve fiber density was higher in the group with endometriosis (0.53 per mm2 ± 0.68) than without endometriosis (0.48 per mm2 ± 0.89), but no statistically significant difference was observed (p > .05). Test specificity was 64.3%, sensitivity 50%, positive predictive value - 61.5%, negative predictive value - 52.9%, and overall accuracy 56.7%. The detection of PGP9.5 positive nerve fibers in eutopic endometrium cannot be used as a reliable diagnostic test of diagnosing endometriosis.
- The Impact of the Ontario Fertility Program on Duplicate Fertility Consultations. [Journal Article]
- HPHealthc Policy 2019; 14(4):66-77
- CONCLUSIONS: The OFP resulted in a statistically significant increase in duplicate consultations, although unlikely to be of clinical relevance. The disproportionate impact seen in the GTA highlights the inequitable access to fertility care in Ontario.
- How Will the New Global Polycystic Ovary Syndrome Guideline Change Our Clinical Practice? [Review]
- CMClin Med Insights Reprod Health 2019; 13:1179558119849605
- Polycystic ovary syndrome (PCOS) is a far reaching condition that has a number of reproductive and general health implications. There has been much debate in recent years about the diagnosis and defi…
Polycystic ovary syndrome (PCOS) is a far reaching condition that has a number of reproductive and general health implications. There has been much debate in recent years about the diagnosis and definition of PCOS and a plethora of studies assessing its management, ranging from the psychosocial aspects of the conditions, to the treatment of hyperandrogenism, anovulatory infertility, and the long-term metabolic and reproductive consequences. There has been a need to synthesise the evidence and produce an international consensus guideline for all aspects of the management of PCOS and this was achieved with the publication of the International evidence-based guideline for the assessment and management of polycystic ovary syndrome. The guideline is broadly categorised into 5 sections, which focus on diagnosis, holistic management and safe, effective fertility treatment. This article summarises the key points of the guidance and brings the management of PCOS up to date for the 21st century.
- Nicotinamide and Demographic and Disease transitions: Moderation is Best. [Review]
- IJInt J Tryptophan Res 2019; 12:1178646919855940
- Good health and rapid progress depend on an optimal dose of nicotinamide. Too little meat triggers the neurodegenerative condition pellagra and tolerance of symbionts such as tuberculosis (TB), riski…
Good health and rapid progress depend on an optimal dose of nicotinamide. Too little meat triggers the neurodegenerative condition pellagra and tolerance of symbionts such as tuberculosis (TB), risking dysbioses and impaired resistance to acute infections. Nicotinamide deficiency is an overlooked diagnosis in poor cereal-dependant economies masquerading as 'environmental enteropathy' or physical and cognitive stunting. Too much meat (and supplements) may precipitate immune intolerance and autoimmune and allergic disease, with relative infertility and longevity, via the tryptophan-nicotinamide pathway. This switch favours a dearth of regulatory T (Treg) and an excess of T helper cells. High nicotinamide intake is implicated in cancer and Parkinson's disease. Pro-fertility genes, evolved to counteract high-nicotinamide-induced infertility, may now be risk factors for degenerative disease. Moderation of the dose of nicotinamide could prevent some common diseases and personalised doses at times of stress or, depending on genetic background or age, may treat some other conditions.
- Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome. [Journal Article]
- RBReprod Biomed Online 2019 Apr 25
- CONCLUSIONS: Addition of cabergoline to GnRH agonist triggering in high-risk OHSS patients, and subsequent addition of GnRH antagonist for 5 days in the luteal phase, sequentially reduces the risk of mild and moderate OHSS and improves patient comfort compared with GnRH agonist trigger alone.
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- "It is a thing that depends on God": barriers to delaying first birth and pursuing alternative futures among newly married adolescent girls in Niger. [Journal Article]
- RHReprod Health 2019 Jul 18; 16(1):109
- CONCLUSIONS: Findings indicate the need for a holistic approach to delaying early birth and stimulating girls' participation in economic and educational pursuits. Potential interventions include mitigating barriers to reproductive health care; training adolescent girls on viable economic activities; and providing educational opportunities for girls. Effective programs should also include or target immediate members of the girls' families (husbands, parents, in-laws), influential local leaders and members of the community at large.