Human Reproduction Update最新文献

{"title":"Navigating parent-child disagreement about fertility preservation in minors: scoping review and ethical considerations.","authors":"Michelle Bayefsky,Dorice Vieira,Arthur Caplan,Gwendolyn Quinn","doi":"10.1093/humupd/dmac019","DOIUrl":"https://doi.org/10.1093/humupd/dmac019","url":null,"abstract":"BACKGROUNDOffering fertility preservation (FP) prior to gonadotoxic therapy, including cancer care and gender-affirming treatment, is now considered standard of care. Periodically, parents and children disagree about whether to pursue FP. However, it is unknown how often this occurs and how disagreement is handled when it arises. Moreover, there is no clear guidance on how to resolve these difficult situations.OBJECTIVE AND RATIONALEThe purpose of this scoping review is to provide an overview of available research evidence about parent-child disagreement regarding FP in order to establish that disagreement occurs in practice, understand the basis for disagreement and explore suggestions for how such disputes could be resolved. Based on our findings, we offer a discussion of the ethical principles at stake when disagreement occurs, which can be used to guide clinicians' approaches when these challenging scenarios present.SEARCH METHODSA comprehensive literature search was run in several databases, including PubMed/Medline, Embase and the Cochrane Library. The search was performed in February 2021 and updated in August 2021. Articles were included in the final review if they discussed how parents or children wanted their views on FP taken into account, presented evidence that parent-child discordance regarding FP exists, discussed how to handle disagreement in a particular case or offered general suggestions for how to approach parent-child discordance about FP. Studies were excluded if the patients were adult only (age 18 years and older), pertained to fertility-sparing treatments (e.g. gonad shielding, gonadopexy) rather than fertility-preserving treatments (e.g. testicular tissue cryopreservation, ovarian tissue cryopreservation, oocyte cryopreservation or sperm cryopreservation) or explored the views of clinicians but not patients or parents. Meta-synthesis was used to synthesize and interpret data across included studies and thematic analysis was used to identify common patterns and themes.OUTCOMESIn total, 755 publications were screened, 118 studies underwent full-text review and 35 studies were included in the final review. Of these studies, 7 discussed how parents or children wanted their opinions to be incorporated, 11 presented evidence that discordance exists between parents and children regarding FP, 4 discussed how disagreement was handled in a particular case and 21 offered general suggestions for how to approach parent-child disagreement. There was a range of study designs, including quantitative and qualitative studies, case studies, ethical analyses and commentaries. From the thematic analysis, four general themes regarding FP disagreement emerged, and four themes relating to the ethical principles at stake in parent-child disagreement were identified. The general themes were: adolescents typically desire to participate in FP decision-making; some parents prefer not to involve their children; minors may feel more favorably about FP","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"962 1","pages":"747-762"},"PeriodicalIF":13.3,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapies to optimize pregnancy outcomes in subfertile women.","authors":"Marcelo Borges Cavalcante,Manoel Sarno,Ricardo Barini","doi":"10.1093/humupd/dmac017","DOIUrl":"https://doi.org/10.1093/humupd/dmac017","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"949 1","pages":"601-602"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenomic and enhancer dysregulation in uterine leiomyomas.","authors":"Oliwia W Mlodawska, Priyanka Saini, J Brandon Parker, Jian-Jun Wei, Serdar E Bulun, Melissa A Simon, Debabrata Chakravarti","doi":"10.1093/humupd/dmac008","DOIUrl":"https://doi.org/10.1093/humupd/dmac008","url":null,"abstract":"<p><strong>Background: </strong>Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common benign gynecological tumors and are found in women of reproductive and postmenopausal age. There is an exceptionally high prevalence of this tumor in women by the age of 50 years. Black women are particularly affected, with an increased incidence, earlier age of onset, larger and faster growing fibroids and greater severity of symptoms as compared to White women. Although advances in identifying genetic and environmental factors to delineate these fibroids have already been made, only recently has the role of epigenomics in the pathogenesis of this disease been considered.</p><p><strong>Objective and rationale: </strong>Over recent years, studies have identified multiple epigenomic aberrations that may contribute to leiomyoma development and growth. This review will focus on the most recent discoveries in three categories of epigenomic changes found in uterine fibroids, namely aberrant DNA methylation, histone tail modifications and histone variant exchange, and their translation into altered target gene architecture and transcriptional outcome. The findings demonstrating how the altered 3D shape of the enhancer can regulate gene expression from millions of base pairs away will be discussed. Additionally, translational implications of these discoveries and potential roadblocks in leiomyoma treatment will be addressed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was performed to identify published articles containing keywords relevant to the focus of the review, such as: uterine leiomyoma, uterine fibroids, epigenetic alterations, epigenomics, stem cells, chromatin modifications, extracellular matrix [ECM] organization, DNA methylation, enhancer, histone post-translational modifications and dysregulated gene expression. Articles until September 2021 were explored and evaluated to identify relevant updates in the field. Most of the articles focused on in the discussion were published between 2015 and 2021, although some key discoveries made before 2015 were included for background information and foundational purposes. We apologize to the authors whose work was not included because of space restrictions or inadvertent omission.</p><p><strong>Outcomes: </strong>Chemical alterations to the DNA structure and of nucleosomal histones, without changing the underlying DNA sequence, have now been implicated in the phenotypic manifestation of uterine leiomyomas. Genome-wide DNA methylation analysis has revealed subsets of either suppressed or overexpressed genes accompanied by aberrant promoter methylation. Furthermore, differential promoter access resulting from altered 3D chromatin structure and histone modifications plays a role in regulating transcription of key genes thought to be involved in leiomyoma etiology. The dysregulated genes function in tumor suppression, apoptosis, angiogenesis, ECM formation, a variety o","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"518-547"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247409/pdf/dmac008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Immunotherapies to optimize pregnancy outcomes in subfertile women.","authors":"Ashleigh Holt-Kentwell,Rima Dhillon-Smith","doi":"10.1093/humupd/dmac018","DOIUrl":"https://doi.org/10.1093/humupd/dmac018","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"943 1","pages":"603-604"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138506313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis.","authors":"Ee Von Woon, Orene Greer, Nishel Shah, Dimitrios Nikolaou, Mark Johnson, Victoria Male","doi":"10.1093/humupd/dmac006","DOIUrl":"10.1093/humupd/dmac006","url":null,"abstract":"<p><strong>Background: </strong>Uterine natural killer cells (uNK) are the most abundant lymphocytes found in the decidua during implantation and in first trimester pregnancy. They are important for early placental development, especially trophoblast invasion and transformation of the spiral arteries. However, inappropriate uNK function has been implicated in reproductive failure, such as recurrent miscarriage (RM) or recurrent implantation failure (RIF). Previous studies have mainly focussed on peripheral NK cells (pNK), despite the well-documented differences in pNK and uNK phenotype and function. In recent years, there has been an explosion of studies conducted on uNK, providing a more suitable representation of the immune environment at the maternal-foetal interface. Here, we summarize the evidence from studies published on uNK in women with RM/RIF compared with controls.</p><p><strong>Objective and rationale: </strong>The objectives of this systematic review and meta-analysis are to evaluate: differences in uNK level in women with RM/RIF compared with controls; pregnancy outcome in women with RM/RIF stratified by high and normal uNK levels; correlation between uNK and pNK in women with RM/RIF; and differences in uNK activity in women with RM/RIF compared with controls.</p><p><strong>Search methods: </strong>MEDLINE, EMBASE, Web of Science and Cochrane Trials Registry were searched from inception up to December 2020 and studies were selected in accordance with PRISMA guidelines. Meta-analyses were performed for uNK level, pregnancy outcome and uNK/pNK correlation. Narrative synthesis was conducted for uNK activity. Risk of bias was assessed by ROBINS-I and publication bias by Egger's test.</p><p><strong>Outcomes: </strong>Our initial search yielded 4636 articles, of which 60 articles were included in our systematic review. Meta-analysis of CD56+ uNK level in women with RM compared with controls showed significantly higher levels in women with RM in subgroup analysis of endometrial samples (standardized mean difference (SMD) 0.49, CI 0.08, 0.90; P = 0.02; I2 88%; 1100 women). Meta-analysis of CD56+ uNK level in endometrium of women with RIF compared with controls showed significantly higher levels in women with RIF (SMD 0.49, CI 0.01, 0.98; P = 0.046; I2 84%; 604 women). There was no difference in pregnancy outcome in women with RM/RIF stratified by uNK level, and no significant correlation between pNK and uNK levels in women with RM/RIF. There was wide variation in studies conducted on uNK activity, which can be broadly divided into regulation and receptors, uNK cytotoxicity, cytokine secretion and effect of uNK on angiogenesis. These studies were largely equivocal in their results on cytokine secretion, but most studies found lower expression of inhibitory receptors and increased expression of angiogenic factors in women with RM.</p><p><strong>Wider implications: </strong>The observation of significantly increased uNK level in endometrium of","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"548-582"},"PeriodicalIF":14.8,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/f9/dmac006.PMC9247428.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10250456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventions to optimize embryo transfer in women undergoing assisted conception: a comprehensive systematic review and meta-analyses.","authors":"Bede Tyler, Hugo Walford, Jennifer Tamblyn, Stephen D Keay, Dimitrios Mavrelos, Ephia Yasmin, Bassel H Al Wattar","doi":"10.1093/humupd/dmac009","DOIUrl":"https://doi.org/10.1093/humupd/dmac009","url":null,"abstract":"<p><strong>Background: </strong>Several interventions and techniques are suggested to improve the outcome of embryo transfer (ET) in assisted conception. However, there remains no consensus on the optimal practice, with high variations among fertility specialists.</p><p><strong>Objective and rationale: </strong>We conducted a comprehensive systematic review and meta-analyses of randomized controlled trials (RCTs) aiming to identify effective interventions that could be introduced around the time of ET to improve reproductive outcomes.</p><p><strong>Search methods: </strong>We searched the electronic databases (MEDLINE, EMBASE and Cochrane CENTRAL) from inception until March 2021 using a multi-stage search strategy of MeSH terms and keywords, and included all RCTs that evaluated an intervention in the 24-h period before/after ET in women undergoing IVF/ICSI. Our primary outcome was clinical pregnancy rate post-ET confirmed as viable pregnancy on ultrasound scan. We assessed the risk of bias in included trials and extracted data in duplicate. We pooled data using a random-effect meta-analysis and reported using risk ratio (RR) with 95% CI. We explored publication bias and effect modifiers using subgroup analyses.</p><p><strong>Outcomes: </strong>Our search yielded 3685 citations of which we included 188 RCTs (38 interventions, 59 530 participants) with a median sample size of 200 (range 26-1761). The quality of included RCTs was moderate with most showing a low risk of bias for randomization (118/188, 62.8%) and attrition (105/188, 55.8%) but there was a significant risk of publication bias (Egger's test P = 0.001). Performing ET with ultrasound guidance versus clinical touch (n = 24, RR 1.265, 95% CI 1.151-1.391, I2 = 38.53%), hyaluronic acid versus routine care (n = 9, RR 1.457, 95% CI 1.197-1.261, I2 = 46.48%) and the use of a soft versus hard catheter (n = 27, RR 1.122, 95% CI 1.028-1.224, I2 = 57.66%) led to higher clinical pregnancy rates. Other pharmacological add-ons also showed a beneficial effect including granulocyte colony-stimulating factor (G-CSF: n = 4, RR 1.774, 95% CI 1.252-2.512, I2 = 0), Atosiban (n = 7, RR 1.493, 95% CI 1.184-1.882, I2 = 68.27%) and hCG (n = 17, RR 1.232, 95% CI 1.099-1.382, I2 = 57.76%). Bed rest following ET was associated with a reduction in clinical pregnancy (n = 6, RR 0.857, 95% CI 0.741-0.991, I2 = 0.01%). Other commonly used interventions, such as non-steroidal anti-inflammatory drugs, prophylactic antibiotics, acupuncture and cervical mucus removal, did not show a significant benefit on reproductive outcomes. Our effect estimates for other important outcomes, including miscarriage and live birth, were limited by the varied reporting across included RCTs.</p><p><strong>Wider implications: </strong>Using ultrasound guidance, soft catheters and hyaluronic acid at the time of ET appears to increase clinical pregnancy rates. The use of Atosiban, G-CSF and hCG showed a trend towards increased clinical pregnan","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 4","pages":"480-500"},"PeriodicalIF":13.3,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10380432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineering trends in female reproduction: a systematic review","authors":"Emilio Francés-Herrero, Rosalba Lopez, M. Hellström, L. de Miguel-Gómez, S. Herraiz, M. Brännström, A. Pellicer, I. Cervelló","doi":"10.1093/humupd/dmac025","DOIUrl":"https://doi.org/10.1093/humupd/dmac025","url":null,"abstract":"Abstract BACKGROUND To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field. OBJECTIVE AND RATIONALE This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman’s syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases. OUTCOMES Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather t","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 1","pages":"798 - 837"},"PeriodicalIF":13.3,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60910529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration of growth hormone improves endometrial function in women undergoing in vitro fertilization: a systematic review and meta-analysis.","authors":"Yujie Shang, Minghua Wu, Ruohang He, Yuanyuan Ye, Xiumei Sun","doi":"10.1093/humupd/dmac028","DOIUrl":"https://doi.org/10.1093/humupd/dmac028","url":null,"abstract":"BACKGROUND\u0000The positive effects of growth hormone (GH) on IVF are often attributed to improvements in oocyte and embryo quality. While emerging evidence emphasizes GH-induced improvements in the endometrium, these results are controversial.\u0000\u0000\u0000OBJECTIVE AND RATIONALE\u0000This meta-analysis aimed to evaluate whether GH administration improved endometrial function and reproductive outcomes during IVF cycles and to thus guide clinical practice.\u0000\u0000\u0000SEARCH METHODS\u0000A literature search in the Cochrane Central Register of Controlled Trials, PubMed and Embase was performed through to 30 November 2021, without language restrictions. Randomized controlled trials (RCTs) evaluating the effects of GH on IVF outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects models.\u0000\u0000\u0000OUTCOMES\u0000A total of 25 trials with 2424 women were included. Seventeen RCTs with poor responders (n = 1723) showed that GH administration significantly increased endometrial thickness (EMT) (MD = 0.38, 95% CI: 0.18-0.59; moderate QoE), which contributed to an improved live birth rate (OR = 1.67, 95% CI: 1.13-2.49; very low QoE) and clinical pregnancy rate (CPR) (OR = 1.97, 95% CI: 1.43-2.72; low QoE). Subgroup analyses showed a dose- and time-dependent relationship between GH cotreatment and IVF outcomes; the optimal recommendation for improving CPR was consistent with that for EMT, rather than for oocytes and embryos. Hence, GH might improve fertility via effects on the endometrium. Administration of GH daily from the follicular phase of previous cycle until the hCG trigger with < 5 IU/day led to a thicker endometrium and a greater chance of becoming pregnant, while 5-10 IU/day or administration from the luteal phase of the previous cycle until the hCG trigger resulted in higher oocyte and embryo quality. Poor responders might benefit from cotreatment with the GnRH agonist long protocol more than other stimulation protocols. Pooled data from four trials (n = 354) on women with a thin endometrium indicated that improved endometrial function might be critical for improving reproductive outcomes during GH treatment, as no improvements in embryo quality were found. GH administration not only increased EMT (MD = 1.48, 95% CI: 1.21-1.75; moderate QoE) but also promoted endometrial morphology (OR = 2.67, 95% CI: 1.36-5.23; low QoE) and perfusion (OR = 5.84, 95% CI: 1.30-26.17; low QoE), thereby improving the CPR (OR = 2.71, 95% CI: 1.69-4.34; P < 0.0001; low QoE). There was insufficient evidence to reach a conclusion regarding the effects of GH in normal responders (n = 80). Due to obvious improvements in the CPR, women with a thin endometrium might be the most appropriate population to benefit from GH administration.\u0000\u0000\u0000WIDER IMPLICATIONS\u0000Imp","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41437769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCL6, a key oncogene, in the placenta, pre-eclampsia and endometriosis","authors":"F. Louwen, N. Kreis, A. Ritter, A. Friemel, C. Solbach, Juping Yuan","doi":"10.1093/humupd/dmac027","DOIUrl":"https://doi.org/10.1093/humupd/dmac027","url":null,"abstract":"Abstract BACKGROUND The key oncogene B-cell lymphoma 6 (BCL6) drives malignant progression by promoting proliferation, overriding DNA damage checkpoints and blocking cell terminal differentiation. However, its functions in the placenta and the endometrium remain to be defined. OBJECTIVE AND RATIONALE Recent studies provide evidence that BCL6 may play various roles in the human placenta and the endometrium. Deregulated BCL6 might be related to the pathogenesis of pre-eclampsia (PE) as well as endometriosis. In this narrative review, we aimed to summarize the current knowledge regarding the pathophysiological role of BCL6 in these two reproductive organs, discuss related molecular mechanisms, and underline associated research perspectives. SEARCH METHODS We conducted a comprehensive literature search using PubMed for human, animal and cellular studies published until October 2021 in the following areas: BCL6 in the placenta, in PE and in endometriosis, in combination with its functions in proliferation, fusion, migration, invasion, differentiation, stem/progenitor cell maintenance and lineage commitment. OUTCOMES The data demonstrate that BCL6 is important in cell proliferation, survival, differentiation, migration and invasion of trophoblastic cells. BCL6 may have critical roles in stem/progenitor cell survival and differentiation in the placenta and the endometrium. BCL6 is aberrantly upregulated in pre-eclamptic placentas and endometriotic lesions through various mechanisms, including changes in gene transcription and mRNA translation as well as post-transcriptional/translational modifications. Importantly, increased endometrial BCL6 is considered to be a non-invasive diagnostic marker for endometriosis and a predictor for poor outcomes of IVF. These data highlight that BCL6 is crucial for placental development and endometrium homeostasis, and its upregulation is associated with the pathogenesis of PE, endometriosis and infertility. WIDER IMPLICATIONS The lesson learned from studies of the key oncogene BCL6 reinforces the notion that numerous signaling pathways and regulators are shared by tumors and reproductive organs. Their alteration may promote the progression of malignancies as well as the development of gestational and reproductive disorders.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"28 1","pages":"890 - 909"},"PeriodicalIF":13.3,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44732534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid metabolism and endometrial receptivity.","authors":"Tianli Yang, Jing Zhao, Feng Liu, Yanping Li","doi":"10.1093/humupd/dmac026","DOIUrl":"https://doi.org/10.1093/humupd/dmac026","url":null,"abstract":"BACKGROUND\u0000Obesity has now been recognized as a high-risk factor for reproductive health. Although remarkable advancements have been made in ART, a considerable number of infertile obese women still suffer from serial implantation failure, despite the high quality of embryos transferred. Although obesity has long been known to exert various deleterious effects on female fertility, the underlying mechanisms, especially the roles of lipid metabolism in endometrial receptivity, remain largely elusive.\u0000\u0000\u0000OBJECTIVE AND RATIONALE\u0000This review summarizes current evidence on the impacts of several major lipids and lipid-derived mediators on the embryonic implantation process. Emerging methods for evaluating endometrial receptivity, for example transcriptomic and lipidomic analysis, are also discussed.\u0000\u0000\u0000SEARCH METHODS\u0000The PubMed and Embase databases were searched using the following keywords: (lipid or fatty acid or prostaglandin or phospholipid or sphingolipid or endocannabinoid or lysophosphatidic acid or cholesterol or progesterone or estrogen or transcriptomic or lipidomic or obesity or dyslipidemia or polycystic ovary syndrome) AND (endometrial receptivity or uterine receptivity or embryo implantation or assisted reproductive technology or in vitro fertilization or embryo transfer). A comprehensive literature search was performed on the roles of lipid-related metabolic pathways in embryo implantation published between January 1970 and March 2022. Only studies with original data and reviews published in English were included in this review. Additional information was obtained from references cited in the articles resulting from the literature search.\u0000\u0000\u0000OUTCOMES\u0000Recent studies have shown that a fatty acids-related pro-inflammatory response in the embryo-endometrium boundary facilitates pregnancy via mediation of prostaglandin signaling. Phospholipid-derived mediators, for example endocannabinoids, lysophosphatidic acid and sphingosine-1-phosphate, are associated with endometrial receptivity, embryo spacing and decidualization based on evidence from both animal and human studies. Progesterone and estrogen are two cholesterol-derived steroid hormones that synergistically mediate the structural and functional alterations in the uterus ready for blastocyst implantation. Variations in serum cholesterol profiles throughout the menstrual cycle imply a demand for steroidogenesis at the time of window of implantation (WOI). Since 2002, endometrial transcriptomic analysis has been serving as a diagnostic tool for WOI dating. Numerous genes that govern lipid homeostasis have been identified and, based on specific alterations of lipidomic signatures differentially expressed in WOI, lipidomic analysis of endometrial fluid provides a possibility for non-invasive diagnosis of lipids alterations during the WOI.\u0000\u0000\u0000WIDER IMPLICATIONS\u0000Given that lipid metabolic dysregulation potentially plays a role in infertility, a better understanding of lipid metabolism could have si","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42730662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}