Reproductive Biology and Endocrinology最新文献

{"title":"Association of LHCGR rs2293275 genotype with ovarian aging in Chinese women: a multicenter population-based study.","authors":"Wenqing Ma, Shuangmei Ye, Lifeng Tian, Min Liu, Rui Wang, Xuezhou Yang, Man Wang, Fangfang Fu, Wu Ren, Lei Dang, Tian Wang, Wenwen Wang, Shixuan Wang, Yan Sun, Yan Li","doi":"10.1186/s12958-025-01375-2","DOIUrl":"10.1186/s12958-025-01375-2","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the association between the LHCGR rs2293275 (N312S) genotype and ovarian aging phenotypes in Han Chinese women, focusing on diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI).</p><p><strong>Study design: </strong>This multicenter population-based study included 1,240 women aged 18-40 years diagnosed with DOR (n = 711) or POI (n = 529), alongside 72,846 ethnically and regionally matched controls from the Han Chinese Genomes Database (PGG.Han). Genotyping of rs2293275 was performed, and clinical data (menstrual history, hormonal profiles, maternal menopause age, and ART outcomes) were analyzed.</p><p><strong>Main results: </strong>The AA genotype frequency in the ovarian aging cohort (1.85%) was significantly higher than in the general Han population (0.62%, OR 3.04, 95% CI 1.99-4.64, p < 0.001). AA carriers exhibited earlier POI diagnosis (25.5 ± 6.4 vs. 32.0 ± 5.1 years in GG carriers, p < 0.001) and maternal menopause (41.6 ± 3.3 vs. 47.8 ± 4.1 years, p < 0.001). In controlled ovarian stimulation cycles, AA carriers demonstrated reduced ovarian sensitivity (OSI: 3.59 vs. 1.21 in GG, p = 0.019) despite comparable gonadotropin doses.</p><p><strong>Conclusions: </strong>The LHCGR rs2293275 AA genotype is strongly associated with accelerated ovarian aging in Han Chinese women, highlighting its potential as a biomarker for early identification of high-risk individuals. While these findings underscore genetic contributions to ovarian dysfunction, further mechanistic studies are needed to establish causality and optimize clinical translation.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov NCT05665010, registered on 2022-11-30.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"41"},"PeriodicalIF":4.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential ability of circulating INSL3 level for the prediction of ovarian reserve and IVF success as a novel theca cell-specific biomarker in women with unexplained infertility and diminished ovarian reserve.","authors":"Pinar Ozcan, F Sezer, A Altun, C Yildiz, H T Timur, E C Keles, O Dural, H S Taha, E Saridogan","doi":"10.1186/s12958-025-01367-2","DOIUrl":"10.1186/s12958-025-01367-2","url":null,"abstract":"<p><strong>Background: </strong>Insulin-like peptide (INSL3), belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Our study investigates if circulating and follicular fluid INSL3 levels serve as biomarkers for ovarian reserve and IVF success in women with unexplained infertility (UI) and diminished ovarian reserve (DOR).</p><p><strong>Methods: </strong>This prospective study included 75 women (25 with DOR, 24 with UI) undergoing IVF and 26 controls with normal ovarian reserve. Serum and follicular fluid INSL3 levels were measured, and their association with ovarian reserve markers, pregnancy rates, and live birth rates (LBR) was analyzed.</p><p><strong>Results: </strong>Circulating (p = 0.001) and follicular fluid (p < 0.001) INSL3 levels, AMH levels (p < 0.001) and AFC (p < 0.001) were significantly lower and basal E2 level (p < 0.001) were significantly higher in DOR group compared to the UI and control groups. Circulating INSL3 positively correlated with serum anti-Müllerian hormone (AMH) and antral follicle count (AFC), and negatively correlated with follicle-stimulating hormone (FSH). Positive pregnancy rates and LBR were significantly lower in the DOR group. Basal FSH was identified as a significant predictor of LBR.</p><p><strong>Conclusions: </strong>The current study presents that although the serum and follicular fluid INSL3 levels are significantly lower in women with DOR, the narrow margin between the DOR and control groups indicates that INSL3measurement may be insufficient on its own to be of diagnostic value for DOR. Further research with larger sample sizes is needed to validate these findings and explore the role of INSL3 in ovarian aging and infertility treatment.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"40"},"PeriodicalIF":4.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic accuracy of preimplantation genetic testing (PGT) in assessing the genetic status of embryos: a systematic review and meta-analysis.","authors":"Kexin Chen, Zhixin Hu, Yuxuan Lian, Youzhen Han, Xiaoting Zhou, Yonggang Li, Lifeng Xiang, Weiqun Jiang, Mingying Li, Peng Zeng, Manqin Zhang, Xi Luo, Yongfang Xu, Haishan Zheng, Mei Tian, Mei Wang, Rui Ma, Jichun Yang, Yun Bai, Ruiyu Du, Bo Deng, Ze Wu, Yunxiu Li, Jiacong Yan","doi":"10.1186/s12958-025-01376-1","DOIUrl":"10.1186/s12958-025-01376-1","url":null,"abstract":"<p><strong>Background: </strong>Preimplantation genetic testing (PGT) is widely used in assisted reproduction to assess the genetic status of embryos. However, increasing evidence suggests that the trophectoderm (TE) may not fully reflect the genetic status of the inner cell mass (ICM), raising controversy about the accuracy of TE biopsy. Research in recent years has focused on cell-free DNA (cfDNA) found in blastocoel fluid (BF) and spent culture medium (SCM), as these may contain genetic information from both the TE and ICM. Therefore, further research and validation are essential to determine the reliability and clinical applicability of these diagnostic methods in PGT.</p><p><strong>Methods: </strong>Relevant studies published between January 2000 and August 2024 were identified through PubMed and Web of Science (WOS). Risk assessment and publication bias were evaluated using QUADAS-2 and Deek's test. Diagnostic meta-analysis was performed using a bivariate model to combine sensitivity and specificity, with results visualized through forest plots and summary receiver operating characteristic (SROC) curves.</p><p><strong>Results: </strong>Out of 6,407 initially screened records, 36 studies involving 4,230 embryos were included. TE biopsy was identified as the best method for diagnosing the genetic status of embryos (sensitivity: 0.839; specificity: 0.791, AUC: 0.878), while SCM had slightly lower accuracy (sensitivity: 0.874; specificity: 0.719, AUC: 0.869). The effectiveness of BF (AUC: 0.656) was significantly lower than that of TE biopsy and SCM. Despite this, TE biopsy has not yet achieved ideal diagnostic performance. However, TE biopsies demonstrate a high level of accuracy in diagnosing PGT-SR (AUC: 0.957). Additionally, multiple TE biopsies (AUC: 0.966) or TE biopsies combined with SCM (AUC: 0.927) can enhance the diagnostic efficiency of PGT.</p><p><strong>Conclusion: </strong>The findings of this study suggest that TE biopsy has yet to achieve optimal diagnostic accuracy, which may result in a significant number of missed embryo diagnoses and misdiagnoses. Our results confirm that SCM has the potential to serve as a supplementary test. Employing multiple biopsies or combining TE with SCM may enhance diagnostic efficiency and yield optimal results.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"39"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of recombinant LH in ovarian stimulation: what's new?","authors":"Carlo Alviggi, Luigi Vigilante, Federica Cariati, Alessandro Conforti, Peter Humaidan","doi":"10.1186/s12958-025-01361-8","DOIUrl":"10.1186/s12958-025-01361-8","url":null,"abstract":"<p><p>It is widely recognized that luteinizing hormone (LH) activity is pivotal during folliculogenesis. Nonetheless, the use of LH during ovarian stimulation remains a matter of debate. Indeed, women with good LH function are able to sustain follicle growth and maturation during ovarian stimulation carried out with regimens based on follicle-stimulating hormone (FSH) alone. However, evidence exists that LH activity could be necessary in specific infertile subgroups undergoing assisted reproduction treatment (ART) who are characterized by a functional or constitutive LH deficiency. For instance, women with reduced sensitivity to gonadotropins, also called hypo-responders, usually present with a genetic condition that could impair the function of LH. Furthermore, women of advanced reproductive age present a less functional LH system and consequently reduced androgen production. Reduced ovarian sensitivity and advanced reproductive age represent the main criteria proposed by the POSEIDON group to identify women with impaired prognosis when undergoing ART. Hypogonadotropic hypogonadal women are characterized by undetectable LH levels, thus the addition of LH activity during stimulation is mandatory to achieve satisfactory follicular recruitment. The aim of the present review is to describe the role of recombinant LH in ovarian stimulation, identifying the specific infertile population for whom LH supplementation could improve the outcome of ART.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 Suppl 1","pages":"38"},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and management of infertility in patients with polycystic ovary syndrome (PCOS): guidelines from the Italian Society of Human Reproduction (SIRU) and the Italian Centers for the Study and Conservation of Eggs and Sperm (CECOS Italy).","authors":"Stefano Palomba, Giuseppe Seminara, Francesco Tomei, Angelo Marino, Giuseppe Morgante, Domenico Baldini, Enrico Papaleo, Guglielmo Ragusa, Antonio Aversa, Adolfo Allegra, Antonino Guglielmino, Edgardo Somigliana","doi":"10.1186/s12958-025-01372-5","DOIUrl":"10.1186/s12958-025-01372-5","url":null,"abstract":"<p><p>The polycystic ovary syndrome (PCOS) is a multifaced disease of the reproductive age associated with several comorbidities including infertility. Very few documents regarding the management of the infertility in women with PCOS, including guidelines, position papers and consensus conferences, are available in the literature. The Italian Law indicates that health professionals must comply with the recommendations set out in the guidelines developed by public and private bodies and institutions, as well as scientific societies and technical-scientific associations of the health professions, except for specific cases. Unfortunately, no guideline for the diagnosis and the management of infertility in women with PCOS is currently available in Italy. In 2024, the Italian Society of Human Reproduction (SIRU) and the Italian Centers for the Study and Conservation of Eggs and Sperm (CECOS Italy) pointed out the need to produce Italian guidelines on this topic and established a specific working group to develop those guidelines. The working group chose to adapt the guideline with highest quality to the Italian context rather than developing a de novo document. The International Evidence-Based Guideline for the Assessment and Management of PCOS guidelines were selected. All recommendations regarding the diagnosis and the management of women with PCOS and infertility extracted, adapted to the Italian context and improved incorporating new recommendations or practical comments and suggestions where needed.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"37"},"PeriodicalIF":4.2,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The composition of human sperm sncRNAome: a cross-country small RNA profiling.","authors":"Poonam Mehta, Rajender Singh","doi":"10.1186/s12958-025-01358-3","DOIUrl":"10.1186/s12958-025-01358-3","url":null,"abstract":"<p><strong>Background: </strong>Over the last decade, numerous studies have implicated sperm-borne small non-coding RNAs (sncRNAs) in fertility and transgenerational inheritance. Spermatozoa contain a variety of small RNAs; however, inter-individual and inter-population variations in the human sperm sncRNA content (sncRNAome) have not yet been ascertained.</p><p><strong>Methods: </strong>We performed sncRNA sequencing in 54 normozoospermic proven fertile Indian donors. We also obtained a second semen sample from 13 donors and a third semen sample from eight donors and repeated sncRNA sequencing. To better understand sperm sncRNAome similarities and variations, sncRNA sequencing data for eligible Chinese (n = 87), US (n = 14), and Spanish (n = 2) normozoospermic (fertile or presumptive fertile) samples were downloaded and analyzed in a uniform manner. sncRNA data were compared within and across populations to identify similarities and differences.</p><p><strong>Results: </strong>In Indian samples, rsRNAs (13.71-78.76%), YsRNAs (0.64-76.53%) and tsRNAs (5.63-35.16%) constituted the major fraction and miRNAs, piRNAs, mt-tsRNAs, and other sncRNAs constituted the minor fraction. Across three other populations, rsRNAs (11-80%) and tsRNAs (10-60%) constituted the major fraction, and YsRNAs (0.62-4.28%), miRNAs (0.41-7.37%), piRNAs (1.37-4.36%), mt-tsRNAs (0.14-4.33%), and other sncRNAs constituted the minor fraction. Only 47 miRNAs were consistent across the Indian samples, and only 17 miRNAs were consistent across the four populations. Interestingly, all piRNAs detected in Indian samples were derived from the chromosome 15 piRNA cluster, which were also predominantly present in other populations. tRNA-Gly-GCC contributed approximately 50% of the tsRNA pool across all populations. The mt-tsRNAs also originated majorly from one mt-tRNA that differed across populations. Among the rsRNAs, the maximum number of reads belonged to 28S, followed by 18S, 5S, 5.8S, and 45S in decreasing order. Y4sRNAs were the most abundant YsRNAs, while the second most common contributor differed across populations.</p><p><strong>Conclusions: </strong>The human sperm sncRNAome has a 'core component' that shows small variations and a 'peripheral component' that shows significant variations across individuals and populations. The availability of the normal human sperm sncRNAome would help delineate biologically meaningful variations from sample-to-sample natural/random variations.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"36"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian stimulation by promoting basal follicular growth.","authors":"Masao Jinno","doi":"10.1186/s12958-025-01356-5","DOIUrl":"10.1186/s12958-025-01356-5","url":null,"abstract":"<p><strong>Background: </strong>Most methods of ovarian stimulation rely on gonadotropin modulation. However, abnormal anti-Müllerian hormone concentrations are frequent in infertility, suggesting that defects in the gonadotropin-independent period of folliculogenesis preceding cyclic recruitment (i.e., basal follicular growth) may often occur. We need to better understand basal follicular growth and determine how to improve it.</p><p><strong>Methods: </strong>Section I summarizes a literature search concerning preantral and early antral folliculogenesis, cyclic recruitment, and selection. Section II presents current knowledge about interventions involving early antral folliculogenesis and cyclic recruitment.</p><p><strong>Results: </strong>While folliculogenesis following cyclic recruitment is gonadotropin-dependent, basal follicular growth is not. Basal follicular growth is regulated by follicle-stimulating hormone and local communication between the oocyte and its granulosa and thecal cells involving gap junctions and many autocrine/paracrine factors. This local communication sustains growth synergistically with follicle-stimulating hormone, but also suppresses this hormone to induce granulosa cell differentiation. As a follicle develops, its responsiveness to gonadotropin progressively increases. Section II describes 4 interventions affecting early antral folliculogenesis, including granulocyte colony-stimulating factor priming, bromocriptine rebound, carbohydrate metabolism intervention, and danazol priming, which have improved embryo development and live birth rate in patients with previous failures.</p><p><strong>Conclusion: </strong>Basal follicular growth modulation can increase live birth rates.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"35"},"PeriodicalIF":4.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ViLR: a novel virtual long read method for breakpoint identification and direct SNP haplotyping in de novo PGT-SR carriers without a proband.","authors":"Jiangyang Xue, Min Xie, Jie Cai, Kai Kang, Mengnan Gu, Mai Li, Haiyue Shi, Xin Zhang, Lingyin Kong, Bo Liang, Liming Zhou, Changshui Chen, Haibo Li","doi":"10.1186/s12958-025-01366-3","DOIUrl":"10.1186/s12958-025-01366-3","url":null,"abstract":"<p><strong>Background: </strong>Despite the gradual application of third-generation long read sequencing (LRS) or reference embryo establishment to preimplantation genetic testing for structural rearrangement (PGT-SR) without familial involvement, there are still limitations to their extensive clinical application yet. This study developed a novel virtual NGS-based long read method (ViLR) and preliminarily evaluated its clinical feasibility of breakpoint characterization and direct SNP haplotyping for de novo chromosomal structural rearrangements (CSR).</p><p><strong>Methods: </strong>A total of 10 families with de novo CSR risk were enrolled in this study for ViLR analysis. In contrast to LRS, ViLR is a virtual long read solution that used the same barcoded labeling and assembly of different long gDNAs differently barcoded. Notably, ViLR could generate an average fragment length of over 30 Kb, with an N50 block size of up to 16 Mb in a single assay, allowing to achieve accurate breakpoint mapping and direct carrier's haplotyping. An approximately 2 Mbp region flanking upstream and downstream of each breakpoint was selected for informative SNP collection. Embryo haplotype determination was based on the established carriers' haplotypes after whole genome amplification and sequencing. To confirm PGT-SR results, we performed prenatal genetic diagnosis.</p><p><strong>Results: </strong>This study achieved an average mapping rate of 99.5%, > 90% coverage depth (> 10X), an average number of effective barcode (> 5 kb length) counts of 11,000,000 and an average fragment length of 40 kb, which generated sufficient informative SNPs for breakpoint characterization and haplotype phasing. ViLR analysis of 10 de novo PGT-SR carriers precisely identified breakpoints and haplotypes. Seven families obtained 18 euploid embryos, in which 10 were euploid/normal embryos, 7 were euploid/balanced carrier embryos, and the remaining one unknown was due to homologous recombination of the breakpoint region. Prenatal genetic diagnosis was performed for four women, and the outcomes coincided with the results from embryo PGT-SR. At the time of writing this paper, four healthy babies had been delivered uneventfully.</p><p><strong>Conclusion: </strong>Here, we demonstrated the clinical potential of ViLR as a novel solution for breakpoint identification and direct SNP haplotyping in de novo PGT-SR families without proband involvement.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"34"},"PeriodicalIF":4.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production.","authors":"Anna-Lena Gehl, Daniel Klawitter, Ulrich Wissenbach, Marnie Cole, Christine Wesely, Heidi Löhr, Petra Weissgerber, Adela Sota, Markus R Meyer, Claudia Fecher-Trost","doi":"10.1186/s12958-025-01362-7","DOIUrl":"10.1186/s12958-025-01362-7","url":null,"abstract":"<p><strong>Background: </strong>The syncytiotrophoblast (STB) layer of the placenta is formed by cell fusion of cytotrophoblasts, acts as a feto-maternal barrier, is required for the production of pregnancy hormones such as chorionic gonadotropin, estradiol and progesterone and is also responsible for feto-maternal mineral exchange such as calcium. Adequate mineral supply and placental hormone production are essential for the maintenance of pregnancy, and disturbances in trophoblast integrity are associated with pregnancy complications. Since knowledge about the identity and expression levels of proteins in trophoblast and syncytiotrophoblast cells is limited so far, we analyzed the proteomes of trophoblast-like and syncytiotrophoblast-like BeWo cells under different calcium conditions. The investigation of protein expression profiles in combination with hormone assays can provide a better understanding of calcium-dependent cellular processes in trophoblasts and syncytiotrophoblasts.</p><p><strong>Methods: </strong>Here, we combine human trophoblast model cell cultures, hormone assays, antibody-based detection methods and high-resolution mass spectrometry analyzes to assess changes in cellular processes during syncytialization.</p><p><strong>Results: </strong>We monitored the changes in protein expression profiles during forskolin induced syncytialization of trophoblast-like cells in an unbiased manner and show that the expression of numerous proteins is strongly altered. Among them are enzymes of the glucocorticoid and sex hormones synthesis pathways such as cytochrome P450 (CYP) 19A1, CYP11A1, adrenodoxin (FDX1), hydroxysteroid dehydrogenase (HSD) 11β2 and HSD17β1, whose expression is strongly induced by syncytialization. The production of beta human chorionic gonadotropin (ß-hCG), progesterone and estradiol increase during syncytialization, while the secretion and synthesis of ß-hCG and the expression of several protein syncytiotrophoblast markers show a clear calcium dependence.</p><p><strong>Conclusion: </strong>The broad applicability of semi-quantitative proteome profiling of cytotrophoblast- and syncytiotrophoblast-like cells provides new insights into signaling processes that occur in cytotrophoblasts /syncytiotrophoblasts during pregnancy.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"33"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation genetic testing for aneuploidy on previously cryopreserved unbiopsied blastocysts: a cohort study in women with IVF pregnancy loss.","authors":"He Cai, Michal Kirshenbaum, Dian Zhang, Haiyan Bai, Wei Li, Xia Xue, Dongyang Wang, XinXiang Wang, Juanzi Shi","doi":"10.1186/s12958-025-01371-6","DOIUrl":"10.1186/s12958-025-01371-6","url":null,"abstract":"<p><strong>Research question: </strong>Does preimplantation genetic testing for aneuploidy (PGT-A) on cryopreserved unbiopsied blastocysts improve pregnancy outcomes for women with previous IVF-related pregnancy loss?</p><p><strong>Methods: </strong>This retrospective observational study included women who underwent vitrified blastocyst warming procedures, with or without trophectoderm biopsy for PGT-A, between January 2016 and June 2023. Participants had experienced two or more clinical pregnancy losses, with at least one loss following in vitro fertilization (IVF). The primary outcome was the cumulative live birth/ongoing pregnancy rate, analyzed using generalized estimating equations (GEE) with confounding adjustments.</p><p><strong>Results: </strong>The cohort included 146 women, comprising 72 who intended to pursue PGT-A on thawed blastocysts (274 blastocysts) and 74 who proceeded directly to frozen embryo transfer (FET) without prior PGT-A (107 blastocysts). Fourteen women in the PGT-A group had no euploid embryos available for transfer. Among these, two patients had no warmed blastocysts suitable for testing, and twelve had all aneuploid embryoid. The cumulative live birth/ongoing pregnancy rate was significantly lower in the PGT-A group compared to the non-PGT-A group (34.7% [25/72] vs. 52.7% [39/74], adjusted odds ratio [AOR] 0.51, 95% confidence interval [CI]: 0.26-0.99, P = 0.048). Secondary outcomes, including live birth and pregnancy loss rates after initial FET, were comparable between the two groups. Among tested blastocysts, 58 (82.9%) had at least one euploid embryo, resulting in a euploidy rate of 48.6% (125/257).</p><p><strong>Conclusions: </strong>PGT-A on cryopreserved unbiopsied blastocysts reduces cumulative live birth/ongoing pregnancy rates and could not improve pregnancy outcomes following the initial FET cycle in women with a history of IVF pregnancy loss.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"31"},"PeriodicalIF":4.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}