Antonio Capalbo, Guido de Wert, Heidi Mertes, Liraz Klausner, Edith Coonen, Francesca Spinella, Hilde Van de Velde, Stephane Viville, Karen Sermon, Nathalie Vermeulen, Todd Lencz, Shai Carmi
<p><strong>Background: </strong>The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing.</p><p><strong>Objective and rationale: </strong>This review has four main goals. First, given the interdisciplinary nature of PES studies, we aim to provide a self-contained educational background about PES to reproductive specialists interested in the subject. Second, we provide a comprehensive and critical review of arguments for and against the introduction of PES, crystallizing and prioritizing the key issues. We also cover the attitudes of IVF patients, clinicians, and the public towards PES. Third, we distinguish between possible future groups of PES patients, highlighting the benefits and harms pertaining to each group. Finally, our review, which is supported by ESHRE, is intended to aid healthcare professionals and policymakers in decision-making regarding whether to introduce PES in the clinic, and if so, how, and to whom.</p><p><strong>Search methods: </strong>We searched for PubMed-indexed articles published between 1/1/2003 and 1/3/2024 using the terms 'polygenic embryo screening', 'polygenic preimplantation', and 'PGT-P'. We limited the review to primary research papers in English whose main focus was PES for medical conditions. We also included papers that did not appear in the search but were deemed relevant.</p><p><strong>Outcomes: </strong>The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases. However, as these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates. PES may negatively impact patients and their future children, as well as society. The main personal harms are an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counselling, and choice overload. The main p
背景：体外受精（IVF）产生的胚胎的基因组成可通过植入前基因检测（PGT）进行检查。直到最近，植入前基因检测还仅限于检测单基因、高风险致病变异、大结构变异和非整倍体。最近的进步使得对试管婴儿胚胎进行全基因组基因分型变得可行且经济实惠，为筛查胚胎罹患乳腺癌、高血压、糖尿病或精神分裂症等多基因疾病的风险提供了可能。尽管围绕这项被称为多基因胚胎筛查（PES；也称 PGT-P）的新技术存在激烈的争论，但在一些国家，试管婴儿患者已经可以使用这项技术。有几篇文章从流行病学、临床和伦理的角度对多基因胚胎筛查进行了研究；然而，目前还缺少对这一新兴领域的全面、有原则的综述。首先，鉴于 PES 研究的跨学科性质，我们旨在为对该主题感兴趣的生殖专家提供有关 PES 的完整教育背景。其次，我们对支持和反对引入 PES 的论点进行了全面和批判性的回顾，并将关键问题具体化和优先化。我们还介绍了试管婴儿患者、临床医生和公众对 PES 的态度。第三，我们对未来可能的 PES 患者群体进行了区分，并强调了与每个群体相关的益处和害处。最后，我们的综述得到了 ESHRE 的支持，旨在帮助医疗保健专业人员和政策制定者就是否在临床中引入 PES，以及如果引入，如何引入和对谁引入做出决策：我们使用 "多基因胚胎筛查"、"多基因植入前 "和 "PGT-P "等词搜索了 2003 年 1 月 1 日至 2024 年 3 月 1 日期间发表的 PubM 索引文章。我们将综述范围限制在主要关注针对医学症状的多基因胚胎筛查的英文初级研究论文。我们还收录了未在搜索中出现但被认为相关的论文：PES 的主要理论益处是降低筛查后出生儿童的终生多基因疾病风险。根据统计建模、模拟和同胞配对分析预测了风险降低的幅度。根据所有方法得出的结果表明，在最佳情况下，一种或多种疾病的相对风险可能会大幅降低。然而，由于这些模型抽象出一些实际限制，实现的收益可能较小，特别是由于胚胎数量有限以及未来风险估计的准确性不明确。PES 可能会对患者及其未来的孩子以及社会产生负面影响。主要的个人危害是不确定的试管婴儿治疗、试管婴儿成功率可能降低、患者困惑、咨询不全面和选择过多。可能造成的主要社会危害包括：胚胎被丢弃、对 "设计婴儿 "的需求不断增加、过分强调疾病的遗传决定因素、获取机会不平等以及非欧洲血统人群的效用较低。主要潜在患者群体（包括已经需要试管婴儿的患者、有严重多基因病史的可育人群和可育的健康人群）的利弊各不相同。在美国，试管婴儿患者和公众对 PES 的态度似乎是积极的，而医疗保健专业人员则持谨慎态度，对临床效用持怀疑态度，并对患者咨询表示担忧：PES在降低多种多基因疾病风险方面的理论潜力需要进一步研究其益处和害处。考虑到大量的实际限制和可能的危害，尤其是不必要的试管婴儿治疗和被丢弃的存活胚胎，在进一步明确其利弊平衡之前，PES 只应在研究背景下提供。需要通过扩大公众和患者教育，提供信息丰富、不偏不倚的遗传咨询资源，来缩小医疗保健专业人员与公众之间的态度差距。
{"title":"Screening embryos for polygenic disease risk: a review of epidemiological, clinical, and ethical considerations.","authors":"Antonio Capalbo, Guido de Wert, Heidi Mertes, Liraz Klausner, Edith Coonen, Francesca Spinella, Hilde Van de Velde, Stephane Viville, Karen Sermon, Nathalie Vermeulen, Todd Lencz, Shai Carmi","doi":"10.1093/humupd/dmae012","DOIUrl":"10.1093/humupd/dmae012","url":null,"abstract":"<p><strong>Background: </strong>The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing.</p><p><strong>Objective and rationale: </strong>This review has four main goals. First, given the interdisciplinary nature of PES studies, we aim to provide a self-contained educational background about PES to reproductive specialists interested in the subject. Second, we provide a comprehensive and critical review of arguments for and against the introduction of PES, crystallizing and prioritizing the key issues. We also cover the attitudes of IVF patients, clinicians, and the public towards PES. Third, we distinguish between possible future groups of PES patients, highlighting the benefits and harms pertaining to each group. Finally, our review, which is supported by ESHRE, is intended to aid healthcare professionals and policymakers in decision-making regarding whether to introduce PES in the clinic, and if so, how, and to whom.</p><p><strong>Search methods: </strong>We searched for PubMed-indexed articles published between 1/1/2003 and 1/3/2024 using the terms 'polygenic embryo screening', 'polygenic preimplantation', and 'PGT-P'. We limited the review to primary research papers in English whose main focus was PES for medical conditions. We also included papers that did not appear in the search but were deemed relevant.</p><p><strong>Outcomes: </strong>The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases. However, as these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates. PES may negatively impact patients and their future children, as well as society. The main personal harms are an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counselling, and choice overload. The main p","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"529-557"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162915","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}
Yican Guo, Liru Xue, Weicheng Tang, Jiaqiang Xiong, Dan Chen, Yun Dai, Chuqing Wu, Simin Wei, Jun Dai, Meng Wu, Shixuan Wang
<p><strong>Background: </strong>Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy.</p><p><strong>Objective and rationale: </strong>This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy.</p><p><strong>Search methods: </strong>A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine).</p><p><strong>Outcomes: </strong>The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, sen
{"title":"Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.","authors":"Yican Guo, Liru Xue, Weicheng Tang, Jiaqiang Xiong, Dan Chen, Yun Dai, Chuqing Wu, Simin Wei, Jun Dai, Meng Wu, Shixuan Wang","doi":"10.1093/humupd/dmae020","DOIUrl":"10.1093/humupd/dmae020","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy.</p><p><strong>Objective and rationale: </strong>This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy.</p><p><strong>Search methods: </strong>A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine).</p><p><strong>Outcomes: </strong>The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, sen","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"614-647"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472813","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}
Sophia Torkel, Rui Wang, Robert J Norman, Lijun Zhao, Kai Liu, Dana Boden, Wentong Xu, Lisa Moran, Stephanie Cowan
Background: While there is a recognized role of optimizing lifestyle (diet and physical activity) behaviours in the management of infertility, the best practice remains unknown and factors influencing the lifestyle of people with infertility are not well understood.
Objective and rationale: This systematic review evaluated barriers and enablers to a healthy lifestyle in people with infertility, from the perspectives of people with infertility and health professionals, in order to inform optimal behavioural change strategies.
Search methods: Ovid MEDLINE(R), PsycINFO, EMBASE, EBM Reviews, and CINAHL were searched from inception to 28 August 2023. Eligible studies were qualitative and quantitative primary studies that explored barriers and/or enablers to lifestyle for infertility management. Quality assessment was performed using the Centre for Evidence-Based Management Critical Appraisal of a Survey Tool and the Critical Appraisal Skills Programme Qualitative Checklist. Data were analysed by thematic analysis with themes mapped to the Capability, Opportunity, Motivation and Behaviour (COM-B) model and Theoretical Domains Framework (TDF).
Outcomes: After screening 12 326 abstracts and 99 full-texts, 27 studies were included (12 quantitative, 6 qualitative and 9 mixed-methods) with 22 studies of women with infertility (n = 2524), 11 studies of men with infertility (n = 1407), and 6 studies of health professionals (n = 372). We identified barriers and enablers relating to capability (e.g. strategies for behaviour change), opportunity (e.g. limited time, resources, and money), and motivation (e.g. interplay between lifestyle and emotional state). Based on the identified themes, suggested intervention components to integrate into lifestyle management of infertility include facilitating development of self-management skills to support lifestyle change (e.g. self-monitoring, action planning, and goal setting) and incorporating mental health strategies (e.g. providing information about the benefits of healthy lifestyle behaviours for mental health and encouraging patients to reframe healthy lifestyle behaviours as self-care strategies).
Wider implications: The findings have identified important factors that influence lifestyle management in people with infertility and have suggested relevant intervention components to consider when designing interventions. Given the paucity of qualitative studies identified, more research is needed to further understand the complex and interacting factors that shape lifestyle during the fertility journey.
{"title":"Barriers and enablers to a healthy lifestyle in people with infertility: a mixed-methods systematic review.","authors":"Sophia Torkel, Rui Wang, Robert J Norman, Lijun Zhao, Kai Liu, Dana Boden, Wentong Xu, Lisa Moran, Stephanie Cowan","doi":"10.1093/humupd/dmae011","DOIUrl":"10.1093/humupd/dmae011","url":null,"abstract":"<p><strong>Background: </strong>While there is a recognized role of optimizing lifestyle (diet and physical activity) behaviours in the management of infertility, the best practice remains unknown and factors influencing the lifestyle of people with infertility are not well understood.</p><p><strong>Objective and rationale: </strong>This systematic review evaluated barriers and enablers to a healthy lifestyle in people with infertility, from the perspectives of people with infertility and health professionals, in order to inform optimal behavioural change strategies.</p><p><strong>Search methods: </strong>Ovid MEDLINE(R), PsycINFO, EMBASE, EBM Reviews, and CINAHL were searched from inception to 28 August 2023. Eligible studies were qualitative and quantitative primary studies that explored barriers and/or enablers to lifestyle for infertility management. Quality assessment was performed using the Centre for Evidence-Based Management Critical Appraisal of a Survey Tool and the Critical Appraisal Skills Programme Qualitative Checklist. Data were analysed by thematic analysis with themes mapped to the Capability, Opportunity, Motivation and Behaviour (COM-B) model and Theoretical Domains Framework (TDF).</p><p><strong>Outcomes: </strong>After screening 12 326 abstracts and 99 full-texts, 27 studies were included (12 quantitative, 6 qualitative and 9 mixed-methods) with 22 studies of women with infertility (n = 2524), 11 studies of men with infertility (n = 1407), and 6 studies of health professionals (n = 372). We identified barriers and enablers relating to capability (e.g. strategies for behaviour change), opportunity (e.g. limited time, resources, and money), and motivation (e.g. interplay between lifestyle and emotional state). Based on the identified themes, suggested intervention components to integrate into lifestyle management of infertility include facilitating development of self-management skills to support lifestyle change (e.g. self-monitoring, action planning, and goal setting) and incorporating mental health strategies (e.g. providing information about the benefits of healthy lifestyle behaviours for mental health and encouraging patients to reframe healthy lifestyle behaviours as self-care strategies).</p><p><strong>Wider implications: </strong>The findings have identified important factors that influence lifestyle management in people with infertility and have suggested relevant intervention components to consider when designing interventions. Given the paucity of qualitative studies identified, more research is needed to further understand the complex and interacting factors that shape lifestyle during the fertility journey.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"569-583"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923857","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":"What is the expected live birth rate per thawed oocyte?","authors":"Raoul Orvieto","doi":"10.1093/humupd/dmae015","DOIUrl":"10.1093/humupd/dmae015","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"648-649"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302131","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":"Correction to: Planned oocyte cryopreservation: a systematic review and meta-regression analysis.","authors":"","doi":"10.1093/humupd/dmae021","DOIUrl":"10.1093/humupd/dmae021","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"651"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472812","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":"Reply: What is the expected live birth rate per thawed oocyte?","authors":"Avi Tsafrir, Ayala Hirsch","doi":"10.1093/humupd/dmae014","DOIUrl":"10.1093/humupd/dmae014","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"650"},"PeriodicalIF":14.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302130","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}
Misung Jo, Mats Brännström, James W Akins, Thomas E Curry
BACKGROUND Successful ovulation is essential for natural conception and fertility. Defects in the ovulatory process are associated with various conditions of infertility or subfertility in women. However, our understanding of the intra-ovarian biochemical mechanisms underlying this process in women has lagged compared to our understanding of animal models. This has been largely due to the limited availability of human ovarian samples that can be used to examine changes across the ovulatory period and delineate the underlying cellular/molecular mechanisms in women. Despite this challenge, steady progress has been made to improve our knowledge of the ovulatory process in women by: (i) collecting granulosa cells across the IVF interval, (ii) creating a novel approach to collecting follicular cells and tissues across the periovulatory period from normally cycling women, and (iii) developing unique in vitro models to examine the LH surge or hCG administration-induced ovulatory changes in gene expression, the regulatory mechanisms underlying the ovulatory changes, and the specific functions of the ovulatory factors. OBJECTIVE AND RATIONALE The objective of this review is to summarize findings generated using in vivo and in vitro models of human ovulation, with the goal of providing new insights into the mechanisms underlying the ovulatory process in women. SEARCH METHODS This review is based on the authors’ own studies and a search of the relevant literature on human ovulation to date using PubMed search terms such as ‘human ovulation EGF-signaling’, ‘human ovulation steroidogenesis’, ‘human ovulation transcription factor’, ‘human ovulation prostaglandin’, ‘human ovulation proteinase’, ‘human ovulation angiogenesis’ ‘human ovulation chemokine’, ‘human ovulatory disorder’, ‘human granulosa cell culture’. Our approach includes comparing the data from the authors’ studies with the existing microarray or RNA-seq datasets generated using ovarian cells obtained throughout the ovulatory period from humans, monkeys, and mice. OUTCOMES Current findings from studies using in vivo and in vitro models demonstrate that the LH surge or hCG administration increases the expression of ovulatory mediators, including EGF-like factors, steroids, transcription factors, prostaglandins, proteolytic systems, and other autocrine and paracrine factors, similar to those observed in other animal models such as rodents, ruminants, and monkeys. However, the specific ovulatory factors induced, their expression pattern, and their regulatory mechanisms vary among different species. These species-specific differences stress the necessity of utilizing human samples to delineate the mechanisms underlying the ovulatory process in women. WIDER IMPLICATIONS The data from human ovulation in vivo and in vitro models have begun to fill the gaps in our understanding of the ovulatory process in women. Further efforts are needed to discover novel ovulatory factors. One approach to address these g
{"title":"New insights into the ovulatory process in the human ovary","authors":"Misung Jo, Mats Brännström, James W Akins, Thomas E Curry","doi":"10.1093/humupd/dmae027","DOIUrl":"https://doi.org/10.1093/humupd/dmae027","url":null,"abstract":"BACKGROUND Successful ovulation is essential for natural conception and fertility. Defects in the ovulatory process are associated with various conditions of infertility or subfertility in women. However, our understanding of the intra-ovarian biochemical mechanisms underlying this process in women has lagged compared to our understanding of animal models. This has been largely due to the limited availability of human ovarian samples that can be used to examine changes across the ovulatory period and delineate the underlying cellular/molecular mechanisms in women. Despite this challenge, steady progress has been made to improve our knowledge of the ovulatory process in women by: (i) collecting granulosa cells across the IVF interval, (ii) creating a novel approach to collecting follicular cells and tissues across the periovulatory period from normally cycling women, and (iii) developing unique in vitro models to examine the LH surge or hCG administration-induced ovulatory changes in gene expression, the regulatory mechanisms underlying the ovulatory changes, and the specific functions of the ovulatory factors. OBJECTIVE AND RATIONALE The objective of this review is to summarize findings generated using in vivo and in vitro models of human ovulation, with the goal of providing new insights into the mechanisms underlying the ovulatory process in women. SEARCH METHODS This review is based on the authors’ own studies and a search of the relevant literature on human ovulation to date using PubMed search terms such as ‘human ovulation EGF-signaling’, ‘human ovulation steroidogenesis’, ‘human ovulation transcription factor’, ‘human ovulation prostaglandin’, ‘human ovulation proteinase’, ‘human ovulation angiogenesis’ ‘human ovulation chemokine’, ‘human ovulatory disorder’, ‘human granulosa cell culture’. Our approach includes comparing the data from the authors’ studies with the existing microarray or RNA-seq datasets generated using ovarian cells obtained throughout the ovulatory period from humans, monkeys, and mice. OUTCOMES Current findings from studies using in vivo and in vitro models demonstrate that the LH surge or hCG administration increases the expression of ovulatory mediators, including EGF-like factors, steroids, transcription factors, prostaglandins, proteolytic systems, and other autocrine and paracrine factors, similar to those observed in other animal models such as rodents, ruminants, and monkeys. However, the specific ovulatory factors induced, their expression pattern, and their regulatory mechanisms vary among different species. These species-specific differences stress the necessity of utilizing human samples to delineate the mechanisms underlying the ovulatory process in women. WIDER IMPLICATIONS The data from human ovulation in vivo and in vitro models have begun to fill the gaps in our understanding of the ovulatory process in women. Further efforts are needed to discover novel ovulatory factors. One approach to address these g","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"30 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328871","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}
Asmamaw Demis Bizuneh, Anju E Joham, Helena Teede, Aya Mousa, Arul Earnest, James M Hawley, Laura Smith, Ricardo Azziz, Wiebke Arlt, Chau Thien Tay
BACKGROUND Biochemical hyperandrogenism is a hallmark and diagnostic feature of polycystic ovary syndrome (PCOS). However, the most accurate androgen measurement for assessing biochemical hyperandrogenism in PCOS diagnosis remains uncertain. OBJECTIVE AND RATIONALE This systematic review aimed to assess different androgen measures [including total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT)] for accuracy in diagnosing biochemical hyperandrogenism in women with PCOS, to inform the 2023 International PCOS Evidence-based Guidelines. SEARCH METHODS To update evidence from the 2018 International PCOS Guidelines, a systematic search from 3 July 2017 to 23 June 2023 was conducted across Medline (Ovid), CINAHL, all EBM, EMBASE, and PsycInfo for articles evaluating androgens in the diagnosis of biochemical hyperandrogenism. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias and applicability. A diagnostic test accuracy meta-analysis was performed using STATA 18 software. Summary sensitivity and specificity were calculated with 95% CIs using the bivariate model, while the hierarchical summary receiver operating characteristics (ROC) model was used to produce a summary ROC curve. OUTCOMES Of 23 studies reviewed, 18 were included in the meta-analysis, with data from 2857 participants (1650 with PCOS and 1207 controls). For diagnosing biochemical hyperandrogenism in PCOS, the pooled sensitivity, specificity, and AUC with 95% CI were for TT: 0.74 (0.63–0.82), 0.86 (0.77–0.91), and 0.87 (0.84–0.90); cFT: 0.89 (0.69–0.96), 0.83 (0.79–0.86), and 0.85 (0.81–0.88); FAI: 0.78 (0.70–0.83), 0.85 (0.76–0.90), and 0.87 (0.84–0.90); A4: 0.75 (0.60–0.86), 0.71 (0.51–0.85), and 0.80 (0.76–0.83); and DHEAS: 0.75 (0.61–0.85), 0.67 (0.48–0.81), and 0.77 (0.73–0.81), respectively. In subgroup analyses, liquid chromatography with tandem mass spectrometry (LC-MS/MS) had superior sensitivity for measuring cFT, FAI, A4, and DHEAS, and superior specificity for measuring TT, cFT, and FAI, compared to the direct immunoassay method. WIDER IMPLICATIONS Our results directly informed the 2023 International PCOS Guideline recommendations to use TT and FT as the first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. cFT should be assessed by equilibrium dialysis or ammonium sulfate precipitation, or calculated using FAI. If TT or cFT are not elevated, A4 and DHEAS could also be considered, noting their poorer specificity. Laboratories should utilize LC-MS/MS for androgen measurement given its high accuracy. Future studies should focus on establishing optimal normative cut-off values in large, unselected, and ethnically diverse cohorts of women. REGISTRATION NUMBER The review protocol was prepublished in the 2023 PCOS Guideline Technical Report (https://www.monash.edu/
{"title":"Evaluating the diagnostic accuracy of androgen measurement in polycystic ovary syndrome: a systematic review and diagnostic meta-analysis to inform evidence-based guidelines","authors":"Asmamaw Demis Bizuneh, Anju E Joham, Helena Teede, Aya Mousa, Arul Earnest, James M Hawley, Laura Smith, Ricardo Azziz, Wiebke Arlt, Chau Thien Tay","doi":"10.1093/humupd/dmae028","DOIUrl":"https://doi.org/10.1093/humupd/dmae028","url":null,"abstract":"BACKGROUND Biochemical hyperandrogenism is a hallmark and diagnostic feature of polycystic ovary syndrome (PCOS). However, the most accurate androgen measurement for assessing biochemical hyperandrogenism in PCOS diagnosis remains uncertain. OBJECTIVE AND RATIONALE This systematic review aimed to assess different androgen measures [including total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT)] for accuracy in diagnosing biochemical hyperandrogenism in women with PCOS, to inform the 2023 International PCOS Evidence-based Guidelines. SEARCH METHODS To update evidence from the 2018 International PCOS Guidelines, a systematic search from 3 July 2017 to 23 June 2023 was conducted across Medline (Ovid), CINAHL, all EBM, EMBASE, and PsycInfo for articles evaluating androgens in the diagnosis of biochemical hyperandrogenism. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias and applicability. A diagnostic test accuracy meta-analysis was performed using STATA 18 software. Summary sensitivity and specificity were calculated with 95% CIs using the bivariate model, while the hierarchical summary receiver operating characteristics (ROC) model was used to produce a summary ROC curve. OUTCOMES Of 23 studies reviewed, 18 were included in the meta-analysis, with data from 2857 participants (1650 with PCOS and 1207 controls). For diagnosing biochemical hyperandrogenism in PCOS, the pooled sensitivity, specificity, and AUC with 95% CI were for TT: 0.74 (0.63–0.82), 0.86 (0.77–0.91), and 0.87 (0.84–0.90); cFT: 0.89 (0.69–0.96), 0.83 (0.79–0.86), and 0.85 (0.81–0.88); FAI: 0.78 (0.70–0.83), 0.85 (0.76–0.90), and 0.87 (0.84–0.90); A4: 0.75 (0.60–0.86), 0.71 (0.51–0.85), and 0.80 (0.76–0.83); and DHEAS: 0.75 (0.61–0.85), 0.67 (0.48–0.81), and 0.77 (0.73–0.81), respectively. In subgroup analyses, liquid chromatography with tandem mass spectrometry (LC-MS/MS) had superior sensitivity for measuring cFT, FAI, A4, and DHEAS, and superior specificity for measuring TT, cFT, and FAI, compared to the direct immunoassay method. WIDER IMPLICATIONS Our results directly informed the 2023 International PCOS Guideline recommendations to use TT and FT as the first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. cFT should be assessed by equilibrium dialysis or ammonium sulfate precipitation, or calculated using FAI. If TT or cFT are not elevated, A4 and DHEAS could also be considered, noting their poorer specificity. Laboratories should utilize LC-MS/MS for androgen measurement given its high accuracy. Future studies should focus on establishing optimal normative cut-off values in large, unselected, and ethnically diverse cohorts of women. REGISTRATION NUMBER The review protocol was prepublished in the 2023 PCOS Guideline Technical Report (https://www.monash.edu/","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"106 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275605","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}
Alexandra E Peters, Emmalee A Ford, Shaun D Roman, Elizabeth G Bromfield, Brett Nixon, Kirsty G Pringle, Jessie M Sutherland
BACKGROUND Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, ‘BPA-free’ alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein. Such damage can diminish reproductive capacity, pregnancy success, and offspring health. Despite global government regulations in place to indicate ‘safe’ BPA exposure levels, these policies have not considered the effects of bisphenols on oocyte health. OBJECTIVE AND RATIONALE This scoping review was conducted to evaluate evidence on the effects of BPA and BPA alternatives on standardized parameters of oocyte health. In doing so, this review addresses a critical gap in the literature providing a comprehensive, up-to-date synthesis of the effects of bisphenols on oocyte health. SEARCH METHODS This scoping review was conducted in accordance with PRISMA guidelines. Four databases, Medline, Embase, Scopus, and Web of Science, were searched twice (23 February 2022 and 1 August 2023) to capture studies assessing mammalian oocyte health post-bisphenol exposure. Search terms regarding oocytes, ovarian follicles, and bisphenols were utilized to identify relevant studies. Manuscripts written in English and reporting the effect of any bisphenol on mammalian oocyte health from all years were included. Parameters for toxicological studies were evaluated, including the number of bisphenol concentrations/doses tested, dosing regimen, biological replicates and/or animal numbers, and statistical information (for human studies). Standardized parameters of oocyte health including follicle counts, oocyte yield, oocyte meiotic capacity, morphology of oocyte and cumulus cells, and oocyte meiotic spindle integrity were extracted across the studies. OUTCOMES After screening 3147 studies, 107 studies of either humans or mammalian animal models or humans were included. Of the in vitro exposure studies, 96.3% (26/27) and 94.1% (16/17) found at least one adverse effect on oocyte health using BPA or BPA alternatives (including BHPF, BPAF, BPB, BPF, and BPS), respectively. These included increased meiotic cell cycle arrest, altered morphology, and abnormal meiotic spindle/chromosomal alignment. In vivo, 85.7% (30/35) of studies on BPA and 92.3% (12/13) on BPA alternatives documented adverse effects on follicle development, morphology, or spindle/chromosome alignment. Importantly, these effects were recorded using levels below those deemed ‘safe’ for human exposure. Over half (11/21) of all human observational studies showed associations between higher urinary BPA levels and reduced antral follicle counts or oocyte yield in IVF patients. Recommendations are presented based on the identified shortcomings of the current e
背景 双酚 A（BPA）是一种干扰内分泌的化学物质，从食品包装和牙科密封剂等塑料材料中释放出来，长期存在于环境中，对生态系统和人类造成普遍污染。双酚 A 可对健康产生一系列有害影响，令人震惊的是，"不含双酚 A "的替代品也反映了这些有害影响。接触双酚会对女性的生育能力产生负面影响，损害卵巢和卵细胞。这种损害会降低生殖能力、怀孕成功率和后代健康。尽管全球政府都制定了相关法规来说明双酚 A 暴露的 "安全 "水平，但这些政策并未考虑双酚对卵母细胞健康的影响。目标和理由 本次范围界定审查旨在评估双酚 A 和双酚 A 替代品对卵母细胞健康标准参数影响的证据。在此过程中，本综述填补了文献中的一个重要空白，就双酚对卵母细胞健康的影响提供了全面、最新的综述。搜索方法 本次范围界定综述根据 PRISMA 指南进行。对 Medline、Embase、Scopus 和 Web of Science 四个数据库进行了两次检索（2022 年 2 月 23 日和 2023 年 8 月 1 日），以获取评估双酚暴露后哺乳动物卵母细胞健康状况的研究。利用有关卵母细胞、卵巢滤泡和双酚的检索词来确定相关研究。收录了用英语撰写的、报告任何双酚对哺乳动物卵母细胞健康影响的历年研究报告。对毒理学研究的参数进行了评估，包括测试的双酚浓度/剂量的数量、剂量方案、生物重复和/或动物数量以及统计信息（针对人类研究）。在所有研究中提取了卵母细胞健康的标准化参数，包括卵泡计数、卵母细胞产量、卵母细胞减数分裂能力、卵母细胞和积层细胞的形态以及卵母细胞减数分裂纺锤体的完整性。结果 筛选了 3147 项研究后，纳入了 107 项关于人类或哺乳动物模型或人类的研究。在体外暴露研究中，分别有 96.3% （26/27）和 94.1% （16/17）的研究发现，使用双酚 A 或双酚 A 替代品（包括双酚 A、双酚 AF、双酚 B、双酚 F 和双酚 S）至少会对卵母细胞健康产生一种不利影响。这些影响包括减数分裂细胞周期停滞、形态改变和减数分裂纺锤体/染色体排列异常。在体内，85.7%（30/35）关于双酚 A 的研究和 92.3%（12/13）关于双酚 A 替代品的研究记录了对卵泡发育、形态或纺锤体/染色体排列的不利影响。重要的是，这些影响都是在低于人体接触 "安全 "水平的情况下产生的。在所有人类观察性研究中，有一半以上（11/21）的研究表明，尿液中双酚 A 水平升高与体外受精患者前卵泡数或卵母细胞产量减少有关。根据已发现的现有证据的不足之处，并结合美国食品及药物管理局（FDA）对该领域未来研究的要求，提出了相关建议。更广泛的影响 这些数据强调了低水平双酚 A 和双酚 A 替代品暴露的有害影响，导致卵母细胞质量差和生育能力下降。这些结果对于推动国际社会修订与双酚 A 暴露相关的现行政策和指导方针具有重要价值。本研究为科学家提供了宝贵的资源，就研究设计、报告要素和终点测量提供了重要建议，以加强未来的研究。最终，本综述强调了卵母细胞健康是生殖毒理学研究中的一个基本重要终点，为今后研究干扰内分泌的化学品以改善生育结果指明了一个重要方向。
{"title":"Impact of Bisphenol A and its alternatives on oocyte health: a scoping review","authors":"Alexandra E Peters, Emmalee A Ford, Shaun D Roman, Elizabeth G Bromfield, Brett Nixon, Kirsty G Pringle, Jessie M Sutherland","doi":"10.1093/humupd/dmae025","DOIUrl":"https://doi.org/10.1093/humupd/dmae025","url":null,"abstract":"BACKGROUND Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, ‘BPA-free’ alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein. Such damage can diminish reproductive capacity, pregnancy success, and offspring health. Despite global government regulations in place to indicate ‘safe’ BPA exposure levels, these policies have not considered the effects of bisphenols on oocyte health. OBJECTIVE AND RATIONALE This scoping review was conducted to evaluate evidence on the effects of BPA and BPA alternatives on standardized parameters of oocyte health. In doing so, this review addresses a critical gap in the literature providing a comprehensive, up-to-date synthesis of the effects of bisphenols on oocyte health. SEARCH METHODS This scoping review was conducted in accordance with PRISMA guidelines. Four databases, Medline, Embase, Scopus, and Web of Science, were searched twice (23 February 2022 and 1 August 2023) to capture studies assessing mammalian oocyte health post-bisphenol exposure. Search terms regarding oocytes, ovarian follicles, and bisphenols were utilized to identify relevant studies. Manuscripts written in English and reporting the effect of any bisphenol on mammalian oocyte health from all years were included. Parameters for toxicological studies were evaluated, including the number of bisphenol concentrations/doses tested, dosing regimen, biological replicates and/or animal numbers, and statistical information (for human studies). Standardized parameters of oocyte health including follicle counts, oocyte yield, oocyte meiotic capacity, morphology of oocyte and cumulus cells, and oocyte meiotic spindle integrity were extracted across the studies. OUTCOMES After screening 3147 studies, 107 studies of either humans or mammalian animal models or humans were included. Of the in vitro exposure studies, 96.3% (26/27) and 94.1% (16/17) found at least one adverse effect on oocyte health using BPA or BPA alternatives (including BHPF, BPAF, BPB, BPF, and BPS), respectively. These included increased meiotic cell cycle arrest, altered morphology, and abnormal meiotic spindle/chromosomal alignment. In vivo, 85.7% (30/35) of studies on BPA and 92.3% (12/13) on BPA alternatives documented adverse effects on follicle development, morphology, or spindle/chromosome alignment. Importantly, these effects were recorded using levels below those deemed ‘safe’ for human exposure. Over half (11/21) of all human observational studies showed associations between higher urinary BPA levels and reduced antral follicle counts or oocyte yield in IVF patients. Recommendations are presented based on the identified shortcomings of the current e","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"8 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233262","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}
Emilie Derisoud, Hong Jiang, Allan Zhao, Pascale Chavatte-Palmer, Qiaolin Deng
<p><strong>Background: </strong>With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types.</p><p><strong>Objective and rationale: </strong>We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases.</p><p><strong>Search methods: </strong>We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types.</p><p><strong>Outcomes: </strong>Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreov
{"title":"Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.","authors":"Emilie Derisoud, Hong Jiang, Allan Zhao, Pascale Chavatte-Palmer, Qiaolin Deng","doi":"10.1093/humupd/dmae006","DOIUrl":"10.1093/humupd/dmae006","url":null,"abstract":"<p><strong>Background: </strong>With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types.</p><p><strong>Objective and rationale: </strong>We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases.</p><p><strong>Search methods: </strong>We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types.</p><p><strong>Outcomes: </strong>Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreov","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"410-441"},"PeriodicalIF":14.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121405","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}
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