Human reproduction open最新文献

{"title":"'There will be blood'^† A proof of concept for the role of haemorrhagic corpora lutea in the pathogenesis of endometriosis.","authors":"Paolo Vercellini, Camilla Erminia Maria Merli, Paola Viganò","doi":"10.1093/hropen/hoae035","DOIUrl":"10.1093/hropen/hoae035","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae035"},"PeriodicalIF":8.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive imaging techniques for diagnosis of pelvic deep endometriosis and endometriosis classification systems: an International Consensus Statement<sup />.","authors":"G Condous, B Gerges, I Thomassin-Naggara, C Becker, C Tomassetti, H Krentel, B J van Herendael, M Malzoni, M S Abrao, E Saridogan, J Keckstein, G Hudelist","doi":"10.1093/hropen/hoae029","DOIUrl":"10.1093/hropen/hoae029","url":null,"abstract":"<p><p>The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), ESHRE, the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers, and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counselling, and planning of surgical treatment strategies.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae029"},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of deep pelvic endometriosis following acute haemoperitoneum: a prospective ultrasound study.","authors":"Prubpreet Chaggar, Tina Tellum, Lucrezia Viola De Braud, Sarah Annie Solangon, Thulasi Setty, Davor Jurkovic","doi":"10.1093/hropen/hoae036","DOIUrl":"10.1093/hropen/hoae036","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), &lt;i&gt;P &lt;/i&gt;=&lt;i&gt; &lt;/i&gt;0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), &lt;i&gt;P &lt;/i&gt;=&lt;i&gt;","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae036"},"PeriodicalIF":8.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of chemical <i>in vitro</i> activation versus fragmentation on human ovarian tissue and follicle growth in culture.","authors":"Jie Hao, Tianyi Li, Manuel Heinzelmann, Elisabeth Moussaud-Lamodière, Filipa Lebre, Kaarel Krjutškov, Anastasios Damdimopoulos, Catarina Arnelo, Karin Pettersson, Ernesto Alfaro-Moreno, Cecilia Lindskog, Majorie van Duursen, Pauliina Damdimopoulou","doi":"10.1093/hropen/hoae028","DOIUrl":"10.1093/hropen/hoae028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the effect of the chemical &lt;i&gt;in vitro&lt;/i&gt; activation (cIVA) protocol compared with fragmentation only (Frag, also known as mechanical IVA) on gene expression, follicle activation and growth in human ovarian tissue &lt;i&gt;in vitro&lt;/i&gt;?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Although histological assessment shows that cIVA significantly increases follicle survival and growth compared to Frag, both protocols stimulate extensive and nearly identical transcriptomic changes in cultured tissue compared to freshly collected ovarian tissue, including marked changes in energy metabolism and inflammatory responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Treatments based on cIVA of the phosphatase and tensin homolog (PTEN)-phosphatidylinositol 3-kinase (PI3K) pathway in ovarian tissue followed by auto-transplantation have been administered to patients with refractory premature ovarian insufficiency (POI) and resulted in live births. However, comparable effects with mere tissue fragmentation have been shown, questioning the added value of chemical stimulation that could potentially activate oncogenic responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Fifty-nine ovarian cortical biopsies were obtained from consenting women undergoing elective caesarean section (C-section). The samples were fragmented for culture studies. Half of the fragments were exposed to bpV (HOpic)+740Y-P (Frag+cIVA group) during the first 24 h of culture, while the other half were cultured with medium only (Frag group). Subsequently, both groups were cultured with medium only for an additional 6 days. Tissue and media samples were collected for histological, transcriptomic, steroid hormone, and cytokine/chemokine analyses at various time points.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Effects on follicles were evaluated by counting and scoring serial sections stained with hematoxylin and eosin before and after the 7-day culture. Follicle function was assessed by quantification of steroids by ultra-performance liquid chromatography tandem-mass spectrometry at different time points. Cytokines and chemokines were measured by multiplex assay. Transcriptomic effects were measured by RNA-sequencing (RNA-seq) of the tissue after the initial 24-h culture. Selected differentially expressed genes (DEGs) were validated by quantitative PCR and immunofluorescence in cultured ovarian tissue as well as in KGN cell (human ovarian granulosa-like tumor cell line) culture experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Compared to the Frag group, the Frag+cIVA group exhibited a significantly higher follicle survival rate, increased numbers of secondary follicles, and larger follicle sizes. Additionally, the tissue in the Frag+cIVA group produced less dehydroepiandrosterone compared to Frag. Cytokine measurement showed a strong inflammatory response at the start of the culture in both groups. The RNA-s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae028"},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Human Reproduction Open</i>, a wild mustang in the prairie of science.","authors":"Edgardo Somigliana, Anja Pinborg, Andrew Williams","doi":"10.1093/hropen/hoae022","DOIUrl":"10.1093/hropen/hoae022","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae022"},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Inaccurate measures of outcomes in the two-sample Mendelian randomization of vitamin D with miscarriage.","authors":"Feng Zhang, Jingtao Huang, Gangting Zhang, Mengyang Dai, Tailang Yin, Chunyu Huang, Jue Liu, Yan Zhang","doi":"10.1093/hropen/hoae026","DOIUrl":"10.1093/hropen/hoae026","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae026"},"PeriodicalIF":8.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inaccurate measures of outcomes in the two-sample Mendelian randomization of vitamin D with miscarriage.","authors":"Qian Yang, Yangbo Sun, Deborah A Lawlor","doi":"10.1093/hropen/hoae025","DOIUrl":"10.1093/hropen/hoae025","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae025"},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 infection in IVF-conceived early pregnancy and the risk of miscarriage: a matched retrospective cohort study.","authors":"Jian Xu, Di Mao, Chunlin Liu, Ling Sun","doi":"10.1093/hropen/hoae024","DOIUrl":"10.1093/hropen/hoae024","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is SARS-CoV-2 infection in IVF-conceived early pregnancy associated with a higher risk of miscarriage?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Infection with SARS-CoV-2 during early pregnancy in women conceiving by IVF may not be associated with an increased rate of miscarriage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;In naturally conceived pregnancies, most findings have shown that SARS-CoV-2 infection does not increase the risk of miscarriage, while some studies have shown that SARS-CoV-2 infection is associated with a higher risk of miscarriage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A matched retrospective cohort study was conducted in a tertiary hospital-based reproductive medicine center. The infection group included women who contracted coronavirus disease 2019 (COVID-19) before 20 weeks gestation from 6 December 2022 to 10 January 2023. Each infected woman was matched with three historical control subjects from 1 January 2018 to 31 May 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The infection group was matched with historical control subjects based on female age (±1 year), number of gestational sacs, number of previous miscarriages, BMI (±2 kg/cm&lt;sup&gt;2&lt;/sup&gt;), main causes of infertility, gestational week, and fresh versus frozen embryo transfer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;A total of 150 pregnant women infected with COVID-19 before 20 weeks of gestation were included in the infection group, which was matched at a 3:1 ratio with 450 historically pregnant controls. There were no significant differences in age, BMI, and endometrial thickness between the two groups. The overall incidence of miscarriage was not significantly different between the infection group and the control group (4.7% versus 5.8%, &lt;i&gt;P&lt;/i&gt; = 0.68). When the infection group was stratified into three subgroups based on the gestational age at the onset of infection (0-7 + 6, 8-11 + 6, and 12-19 + 6 weeks), no significant differences were observed in the incidence of miscarriage between the infection group and the matched control group in any of the subgroups (9.8% versus 13.8%, &lt;i&gt;P&lt;/i&gt; = 0.60; 5.4% versus 4.5%, &lt;i&gt;P&lt;/i&gt; = 1.00; and 1.4% versus 1.9%, &lt;i&gt;P&lt;/i&gt; = 1.00, respectively).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The major limitation of this study is the relatively small sample size; therefore, caution is suggested when drawing any definitive conclusions. Nonetheless, our study is the largest sample study of the influence of COVID-19 infection on the miscarriage rate in early pregnancy after IVF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;Our findings may provide important insights for reproductive physicians and obstetricians during preconception and early pregnancy counseling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interests: &lt;/strong&gt;This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A15","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae024"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells.","authors":"Sofia Makieva, Elisa Giacomini, Giulia Maria Scotti, Dejan Lazarevic, Valentina Pavone, Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Marco Morelli, Alessandra Alteri, Sabrina Minetto, Giovanni Tonon, Massimo Candiani, Enrico Papaleo, Paola Viganò","doi":"10.1093/hropen/hoae014","DOIUrl":"10.1093/hropen/hoae014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Aneuploid embryo-derived EVs contain transcripts of &lt;i&gt;PPM1J&lt;/i&gt;, &lt;i&gt;LINC00561&lt;/i&gt;, &lt;i&gt;ANKRD34C&lt;/i&gt;, and &lt;i&gt;TMED10&lt;/i&gt; with differential abundance from euploid embryo-derived EVs and induce upregulation of &lt;i&gt;MUC1&lt;/i&gt; transcript in dESCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes &lt;i&gt;PPM1J&lt;/i&gt; (log2fc = -5.13, &lt;i&gt;P&lt;/i&gt; = 0.011), &lt;i&gt;LINC00561&lt;/i&gt; (log2fc = -7.87, &lt;i&gt;P&lt;/i&gt; = 0.010), and &lt;i&gt;ANKRD34C&lt;/i&gt; (log2fc = -7.30, &lt;i&gt;P&lt;/i&gt; = 0.017) and more abundant in &lt;i&gt;TMED10&lt;/i&gt; (log2fc = 1.63, &lt;i&gt;P&lt;/i&gt; = 0.025) compared to EVs of euploid embryos. Decidualization &lt;i&gt;per se&lt;/i&gt; induced downregulation of &lt;i&gt;MUC1&lt;/i&gt; (log2fc = -0.54, &lt;i&gt;P&lt;/i&gt; = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of &lt;i&gt;MUC1&lt;/i&gt; transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, &lt;i&gt;P&lt;/i&gt; = 0.0201).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;Raw data have been uploaded to GEO (accession number GSE234338).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The findings of the study will require validation utilizing a second cohort of EV samples.&lt;/p&gt;&lt;p&gt;&lt;stro","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae014"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.","authors":"Xinyu Li, Yunying Lin, Xiaoyue Cheng, Guangxin Yao, Jufang Yao, Shuanggang Hu, Qinling Zhu, Yuan Wang, Ying Ding, Yao Lu, Jia Qi, Hanting Zhao, Xuejiao Bian, Yanzhi Du, Kang Sun, Hugo Vankelecom, Yun Sun","doi":"10.1093/hropen/hoae013","DOIUrl":"10.1093/hropen/hoae013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed &lt;i&gt;in vitro&lt;/i&gt; using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored &lt;i&gt;in vivo&lt;/i&gt; in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe&lt;sup&gt;2+&lt;/sup&gt; (&lt;i&gt;P","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 2","pages":"hoae013"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}