Publications by authors named "Jie Qiao"

563 Publications

DNA methylome reveals cellular origin of cell-free DNA in spent medium of human preimplantation embryos.

J Clin Invest 2021 Jun;131(12)

Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, and.

The discovery of embryonic cell-free DNA (cfDNA) in spent embryo culture media (SECM) has brought hope for noninvasive preimplantation genetic testing. However, the cellular origins of SECM cfDNA are not sufficiently understood, and methods for determining maternal DNA contamination are limited. Here, we performed whole-genome DNA methylation sequencing for SECM cfDNA. Our results demonstrated that SECM cfDNA was derived from blastocysts, cumulus cells, and polar bodies. We identified the cumulus-specific differentially methylated regions (DMRs) and oocyte/polar body-specific DMRs, and established an algorithm for deducing the cumulus, polar body, and net maternal DNA contamination ratios in SECM. We showed that DNA methylation sequencing accurately detected chromosome aneuploidy in SECM and distinguished SECM samples with low and high false negative rates and gender discordance rates, after integrating the origin analysis. Our work provides insights into the characterization of embryonic DNA in SECM and provides a perspective for noninvasive preimplantation genetic testing in reproductive medicine.
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http://dx.doi.org/10.1172/JCI146051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203451PMC
June 2021

Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology.

Front Endocrinol (Lausanne) 2021 28;12:667422. Epub 2021 May 28.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. PCOS patients are characterized by hyperandrogenemia, anovulation, and metabolic dysfunction. Hypothalamus-pituitary-ovary axis imbalance is considered as an important pathophysiology underlying PCOS, indicating that central modulation, especially the abnormal activation of hypothalamic GnRH neurons plays a vital role in PCOS development. Increased GnRH pulse frequency can promote LH secretion, leading to ovarian dysfunction and abnormal sex steroids synthesis. By contrast, peripheral sex steroids can modulate the action of GnRH neurons through a feedback effect, which is impaired in PCOS, thus forming a vicious cycle. Additionally, hypothalamic GnRH neurons not only serve as the final output pathway of central control of reproductive axis, but also as the central connection point where reproductive function and metabolic state inter-regulate with each other. Metabolic factors, such as insulin resistance and obesity in PCOS patients can regulate GnRH neurons activity, and ultimately regulate reproductive function. Besides, gut hormones act on both brain and peripheral organs to modify metabolic state. Gut microbiota disturbance is also related to many metabolic diseases and has been reported to play an essential part in PCOS development. This review concludes with the mechanism of central modulation and the interaction between neuroendocrine factors and reproductive or metabolic disorders in PCOS development. Furthermore, the role of the gut microenvironment as an important part involved in the abnormal neuronal-reproductive-metabolic circuits that contribute to PCOS is discussed, thus offering possible central and peripheral therapeutic targets for PCOS patients.
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http://dx.doi.org/10.3389/fendo.2021.667422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194358PMC
May 2021

Regional Variation of Early-onset Neonatal Group B Streptococcal Disease Prevention Strategies in Mainland China.

Pediatr Infect Dis J 2021 Jul;40(7):663-668

Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California.

Background: Prevention strategies can reduce the incidence of early-onset group B Streptococcus (GBS) neonatal sepsis (EOGBS). Rates of GBS colonization and infection vary among regions within China. China has not adopted a unified prevention strategy.

Methods: To assess strategies to reduce EOGBS in China, models were developed to quantify residual EOGBS rates with intrapartum antibiotic prophylaxis in infants ≥ 35 weeks' gestation in risk factor-based and antepartum screening-based strategies. Maternal GBS colonization rates and EOGBS incidence in 3 regions of China (A: Xiamen of Fujian province, B: Shanghai and C: Liuzhou of Guangxi province) were estimated from published data.

Results: Estimates for GBS colonization and attack rates were 21.6%, 11.7% and 6.1% and 1.79, 1.79 and 0.58 per 1000 live births for regions A, B and C, respectively. Modeling predicted that strategies including screening cultures beginning at 36 weeks' gestation and intrapartum antibiotic prophylaxis in 90% of eligible parturients could reduce EOGBS incidence to 0.44, 0.50 and 0.16 per 1000 live births in these regions. In region C, the expected EOGBS rate could be reduced to 0.28 per 1000 using a risk factor-based strategy.

Conclusions: Different strategies for preventing EOGBS may be needed in different regions of mainland China. Screening strategies may be most appropriate in regions with higher attack rates, even with moderate levels of maternal GBS colonization. In areas with low attack rates, risk factor strategies that reduce morbidity by at least one-third may suffice.
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http://dx.doi.org/10.1097/INF.0000000000003089DOI Listing
July 2021

DevOmics: an integrated multi-omics database of human and mouse early embryo.

Brief Bioinform 2021 Jun 7. Epub 2021 Jun 7.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Transcriptomic and epigenetic alterations during early embryo development have been proven to play essential roles in regulating the cell fate. Nowadays, advances in single-cell transcriptomics and epigenomics profiling techniques provide large volumes of data for understanding the molecular regulatory mechanisms in early embryos and facilitate the investigation of assisted reproductive technology as well as preimplantation genetic testing. However, the lack of integrated data collection and unified analytic procedures greatly limits their usage in scientific research and clinical application. Hence, it is necessary to establish a database integrating the regulatory information of human and mouse early embryos with unified analytic procedures. Here, we introduce DevOmics (http://devomics.cn/), which contains normalized gene expression, DNA methylation, histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac), chromatin accessibility and 3D chromatin architecture profiles of human and mouse early embryos spanning six developmental stages (zygote, 2cell, 4cell, 8cell, morula and blastocyst (ICM, TE)). The current version of DevOmics provides Search and Advanced Search for retrieving genes a researcher is interested in, Analysis Tools including the differentially expressed genes (DEGs) analysis for acquiring DEGs between different types of samples, allelic explorer for displaying allele-specific gene expression as well as epigenetic modifications and correlation analysis for showing the dynamic changes in different layers of data across developmental stages, as well as Genome Browser and Ortholog for visualization. DevOmics offers a user-friendly website for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryos.
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http://dx.doi.org/10.1093/bib/bbab208DOI Listing
June 2021

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China.

Chin Med J (Engl) 2021 Jun 4;134(12):1405-1415. Epub 2021 Jun 4.

Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.

Background: More and more scholars have called for the cumulative live birth rate (CLBR) of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology. This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.

Methods: Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles performed between January 2013 to December 2014. A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included. The study was followed up for 4 years to observe the CLBR. The multivariable logistic regression model was used to analyze the prognosis factor, P value of <0.05 was considered statistically significant.

Results: The cumulative pregnancy rate was 58.14% (10,452/17,978), and the CLBR was 49.66% (8928/17,978). The female age was younger in the live birth group when compared with the non-live birth group (30.81 ± 4.05 vs. 33.09 ± 5.13, P < 0.001). The average duration of infertility was shorter than the non-live birth cohort (4.22 ± 3.11 vs. 5.06 ± 4.08, P < 0.001). The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group (both P < 0.001). Meanwhile, the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group (15.35 ± 7.98 vs. 11.35 ± 7.60, P < 0.001; 6.66 ± 5.19 vs. 3.62 ± 3.51, P < 0.001, respectively).

Conclusions: The women's age, body mass index, duration of infertility years, infertility factors, controlled ovarian hyperstimulation protocol, the number of acquired oocytes, and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.
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http://dx.doi.org/10.1097/CM9.0000000000001586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213303PMC
June 2021

Analysis of in vitro fertilization/intracytoplasmic sperm injection outcomes in infertile women with a history of thyroid cancer: a retrospective study.

Reprod Biol Endocrinol 2021 Jun 4;19(1):82. Epub 2021 Jun 4.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 49 North Garden Rd, Beijing, 100191, China.

Background: Recent studies have revealed that women with infertility have a higher risk of thyroid cancer (TC) than fertile women. However, studies on whether a history of thyroid cancer affects clinical outcomes in women who conceive using in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) are scarce. We investigate whether a history of thyroid cancer (TC) affects the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and increases the risk of adverse obstetric outcomes in women with infertility.

Methods: This retrospective study enrolled 384 women with infertility who underwent their first IVF/ICSI treatment at the Peking University Third Hospital between 2010 and 2019. Participants were divided into the TC (64 women with TC history) and control (320 women matched from 85,272 women without thyroid diseases) groups. Controls were individually matched to the TC group according to age, body mass index, concomitant infertility factors, first IVF/ICSI dates, and controlled ovarian stimulation and embryo transfer procedure protocols. IVF/ICSI outcomes, including the numbers of retrieved oocytes and high-grade embryos, clinical pregnancy, miscarriage, preterm delivery, and live birth rates, and adverse obstetric outcome risk were assessed.

Results: The TC group had significantly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels than the control group. Despite similar gonadotropin treatment dosage, the TC group had a significantly lower numbers of retrieved oocytes and high-grade embryos than the control group. The occurrence rates of clinical pregnancy, miscarriage, preterm delivery, live births, and adverse obstetric outcomes, including multiple gestation, preterm delivery, gestational diabetes mellitus, gestational hypertension, low birth weight, and large-for-gestational-age infants, were not significantly different between the two groups.

Conclusions: TC history did not affect the pregnancy outcomes or increase the risk of adverse obstetric outcomes after the first IVF/ICSI, but it may decrease the number of retrieved oocytes and high-grade embryos.
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http://dx.doi.org/10.1186/s12958-021-00763-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176716PMC
June 2021

Intrauterine insemination (IUI) with or without letrozole for unexplained or mild male factor infertility: A randomized pilot study.

Eur J Obstet Gynecol Reprod Biol 2021 May 15;262:216-220. Epub 2021 May 15.

Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.

Objective: To study the feasibility of a randomized controlled trial (RCT) comparing intrauterine insemination (IUI) with and without letrozole in couples with unexplained or mild male factor infertility STUDY DESIGN: We performed a randomized pilot study including 100 couples with unexplained or mild male factor infertility in the Reproductive Medicine Centre of Peking University Third Hospital in China. The couples scheduled for IUI were randomized to IUI with or without ovarian stimulation (letrozole) for up to 3 cycles within a time horizon of 4 months. Women in the letrozole group received 5 mg oral letrozole daily starting from cycle day 3-5 for 5 days. Women in the natural cycle IUI group did not receive any ovarian stimulation before IUI. The primary outcome is ongoing pregnancy leading to live birth. The study was registered under trial number NCT03455426 RESULTS: Between March 2018 and January 2019, 158 couples were eligible to participate after initial screening and 100 (63.3 %) couples agreed to participate. Of the 100 recruited couples, 50 were randomly allocated to IUI with letrozole and 50 to natural cycle IUI. Live birth occurred in 12 women (24.0 %) in the letrozole group and 10 women (20.0 %) in the natural cycle group (RR 1.20 (95 % CI 0.57-2.52)). Clinical pregnancy rates were 28 % and 26 % in the letrozole group and natural cycle group respectively (RR 1.08 (95 % CI 0.56-2.05). There were no multiple pregnancies in both groups. Patients were willing to be randomized and useful information was gained to plan a definitive trial.

Conclusions: We showed that an RCT comparing IUI with letrozole versus natural cycle IUI in couples with unexplained or mild male factor infertility is feasible and acceptable.
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http://dx.doi.org/10.1016/j.ejogrb.2021.05.029DOI Listing
May 2021

OP-IVM: Combining In vitro Maturation after Oocyte Retrieval with Gynecological Surgery.

J Vis Exp 2021 May 9(171). Epub 2021 May 9.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital; National Clinical Research Center for Obstetrics and Gynecology; Key Laboratory of Assisted Reproduction, Ministry of Education; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction; Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences;

The use of in vitro maturation (IVM) before gynecological operation (OP-IVM) is an extension of conventional IVM that combines IVM following oocyte retrieval with routine gynecological surgery. OP-IVM is suitable for patients undergoing benign gynecological surgery who have the need for fertility preservation (FP) or infertility treatments such as in vitro fertilization and embryo transfer (IVF-ET). In the operating room, patients undergoing benign gynecological surgery are first anesthetized and receive ultrasound-guided immature follicle aspiration (IMFA) treatment. As the subsequent gynecological surgery is performed, the cumulus-oocyte complexes (COCs) are examined, and the immature COCs are transferred into the IVM medium and cultured for 28-32 hours in the IVF laboratory. After assessment, mature oocytes in the MII stage will be selected and cryopreserved in liquid nitrogen for FP or fertilized by intracytoplasmic sperm injection (ICSI) for IVF-ET. By combining IVM with gynecological surgery, immature oocytes that would have been discarded can be saved and used for assisted reproductive technology (ART). The procedure, significance and critical aspects of OP-IVM are described in this article.
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http://dx.doi.org/10.3791/61647DOI Listing
May 2021

Mitochondrial proteome of mouse oocytes and cisplatin-induced shifts in protein profile.

Acta Pharmacol Sin 2021 May 20. Epub 2021 May 20.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.

Mitochondria are essential organelles that provide energy for mammalian cells and participate in multiple functions, such as signal transduction, cellular differentiation, and regulation of apoptosis. Compared with the mitochondria in somatic cells, oocyte mitochondria have an additional level of importance since they are required for germ cell maturation, dysfunction in which can lead to severe inherited disorders. Thus, a systematic proteomic profile of oocyte mitochondria is urgently needed to support the basic and clinical research, but the acquisition of such a profile has been hindered by the rarity of oocyte samples and technical challenges associated with capturing mitochondrial proteins from live oocytes. Here, in this work, using proximity labeling proteomics, we established a mitochondria-specific ascorbate peroxidase (APEX2) reaction in live GV-stage mouse oocytes and identified a total of 158 proteins in oocyte mitochondria. This proteome includes intrinsic mitochondrial structural and functional components involved in processes associated with "cellular respiration", "ATP metabolism", "mitochondrial transport", etc. In addition, mitochondrial proteome capture after oocyte exposure to the antitumor chemotherapeutic cisplatin revealed differential changes in the abundance of several oocyte-specific mitochondrial proteins. Our study provides the first description of a mammalian oocyte mitochondrial proteome of which we are aware, and further illustrates the dynamic shifts in protein abundance associated with chemotherapeutic agents.
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http://dx.doi.org/10.1038/s41401-021-00687-4DOI Listing
May 2021

Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.

Sleep Breath 2021 May 19. Epub 2021 May 19.

Reproductive Medical Center, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.

Purpose: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients.

Methods: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA.

Results: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05).

Conclusion: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.
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http://dx.doi.org/10.1007/s11325-021-02376-2DOI Listing
May 2021

Effects of SARS-CoV-2 infection on human reproduction.

J Mol Cell Biol 2021 May 18. Epub 2021 May 18.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China.

The worldwide infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts human health and life on multiple levels. People infected with SARS-CoV-2 suffer from physical disorders and psychological distress. At present, no direct evidence indicates that SARS-CoV-2 negatively influences human reproduction, and the possibility that gametes and embryos are affected requires further investigation. To evaluate the potential effects of SARS-CoV-2 infection on human reproduction and fetal health, this review summarizes the basic and clinical research of SARS-CoV-2 on reproduction up to date, hoping to offer guidance and advice to people at reproductive age and provide clues for the prevention and treatment of associated diseases.
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http://dx.doi.org/10.1093/jmcb/mjab025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194633PMC
May 2021

Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis.

Cell Death Dis 2021 May 12;12(5):478. Epub 2021 May 12.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

The spermatogenesis process is complex and delicate, and any error in a step may cause spermatogenesis arrest and even male infertility. According to our previous transcriptomic data, CEP70 is highly expressed throughout various stages of human spermatogenesis, especially during the meiosis and deformation stages. CEP70 is present in sperm tails and that it exists in centrosomes as revealed by human centrosome proteomics. However, the specific mechanism of this protein in spermatogenesis is still unknown. In this study, we found a heterozygous site of the same mutation on CEP70 through mutation screening of patients with clinical azoospermia. To further verify, we deleted CEP70 in mice and found that it caused abnormal spermatogenesis, leading to male sterility. We found that the knockout of CEP70 did not affect the prophase of meiosis I, but led to male germ-cell apoptosis and abnormal spermiogenesis. By transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analysis, we found that the deletion of CEP70 resulted in the abnormal formation of flagella and acrosomes during spermiogenesis. Tandem mass tag (TMT)-labeled quantitative proteomic analysis revealed that the absence of CEP70 led to a significant decrease in the proteins associated with the formation of the flagella, head, and acrosome of sperm, and the microtubule cytoskeleton. Taken together, our results show that CEP70 is essential for acrosome biogenesis and flagella formation during spermiogenesis.
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http://dx.doi.org/10.1038/s41419-021-03755-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116340PMC
May 2021

A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband.

J Assist Reprod Genet 2021 May 3. Epub 2021 May 3.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49, North Garden Road, Haidian District, Beijing, 100191, People's Republic of China.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the development of renal cysts and progression to renal failure. Preimplantation genetic testing-monogenic disease (PGT-M) is an alternative option to obtain healthy babies. However, de novo PKD1 mutation of one of the spouses or the absence of a positive family history poses a serious challenge to PGT-M. Here, we described a comprehensive strategy which includes preimplantation genetic testing for aneuploidies (PGT-A) study and monogenic diagnosis study for ADPKD patients bearing de novo mutations. The innovation of our strategy is to use the gamete (polar body or single sperm) as proband for single-nucleotide polymorphism (SNP) linkage analysis to detect an embryo's carrier status. Nine ADPKD couples with either de novo mutation or without a positive family history were recruited and a total of 34 embryos from 13 PGT-M cycles were examined. Within these nine couples, two successfully delivered healthy babies had their genetic status confirmed by amniocentesis. This study provides a creative approach for embryo diagnosis of patients with de novo mutations or patients who lack essential family members for linkage analysis.
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http://dx.doi.org/10.1007/s10815-021-02188-zDOI Listing
May 2021

PPP2R1B is modulated by ubiquitination and is essential for spermatogenesis.

FASEB J 2021 May;35(5):e21564

Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing, China.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme complex that regulates many fundamental cellular processes. PP2A is involved in tumorigenesis because mutations in the scaffold subunit, PPP2R1B, were found in several types of cancers. However, the biological function of PPP2R1B remains largely unknown. We report here that homozygous deletion of Ppp2r1b in Mus musculus impairs meiotic recombination and causes meiotic arrest in spermatocytes. Consistently, male mice lacking Ppp2r1b are characterized with infertility. Furthermore, heterozygous missense mutations in the Homo sapiens PPP2R1B gene, which encodes PPP2R1B, are identified in azoospermia patients with meiotic arrest. We found that PPP2R1B mutants are susceptible to degradation by an E3 ligase CRL4A , and resistant to de-polyubiquitylation by ubiquitin-specific protease 5 (USP5). In addition, heterozygous mutations in PPP2R1B reduce stability of the wild-type PPP2R1B. Our results demonstrate an essential role of PPP2R1B in spermatogenesis and identify upstream regulators of PPP2R1B.
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http://dx.doi.org/10.1096/fj.202002810RDOI Listing
May 2021

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility.

J Assist Reprod Genet 2021 Apr 26. Epub 2021 Apr 26.

Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, 49 North Garden Rd, Beijing, 100191, China.

Purpose: We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes.

Methods: This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed.

Results: We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity.

Conclusion: Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.
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http://dx.doi.org/10.1007/s10815-021-02204-2DOI Listing
April 2021

Full-length SMRT transcriptome sequencing and microsatellite characterization in Paulownia catalpifolia.

Sci Rep 2021 Apr 22;11(1):8734. Epub 2021 Apr 22.

Paulownia Research and Development Center of State Administration of Forestry and Grassland, Zhengzhou, 450003, China.

Paulownia catalpifolia is an important, fast-growing timber species known for its high density, color and texture. However, few transcriptomic and genetic studies have been conducted in P. catalpifolia. In this study, single-molecule real-time sequencing technology was applied to obtain the full-length transcriptome of P. catalpifolia leaves treated with varying degrees of drought stress. The sequencing data were then used to search for microsatellites, or simple sequence repeats (SSRs). A total of 28.83 Gb data were generated, 25,969 high-quality (HQ) transcripts with an average length of 1624 bp were acquired after removing the redundant reads, and 25,602 HQ transcripts (98.59%) were annotated using public databases. Among the HQ transcripts, 16,722 intact coding sequences, 149 long non-coding RNAs and 179 alternative splicing events were predicted, respectively. A total of 7367 SSR loci were distributed throughout 6293 HQ transcripts, of which 763 complex SSRs and 6604 complete SSRs. The SSR appearance frequency was 28.37%, and the average distribution distance was 5.59 kb. Among the 6604 complete SSR loci, 1-3 nucleotide repeats were dominant, occupying 97.85% of the total SSR loci, of which mono-, di- and tri-nucleotide repeats were 44.68%, 33.86% and 19.31%, respectively. We detected 112 repeat motifs, of which A/T (42.64%), AG/CT (12.22%), GA/TC (9.63%), GAA/TTC (1.57%) and CCA/TGG (1.54%) were most common in mono-, di- and tri-nucleotide repeats, respectively. The length of the repeat SSR motifs was 10-88 bp, and 4997 (75.67%) were ≤ 20 bp. This study provides a novel full-length transcriptome reference for P. catalpifolia and will facilitate the identification of germplasm resources and breeding of new drought-resistant P. catalpifolia varieties.
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http://dx.doi.org/10.1038/s41598-021-87538-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062547PMC
April 2021

"Aptamer-locker" DNA coupling with CRISPR/Cas12a-guided biosensing for high-efficiency melamine analysis.

Biosens Bioelectron 2021 Jul 7;183:113233. Epub 2021 Apr 7.

State Key Laboratory of Biocatalysts and Enzyme Engineering, Hubei University, China; Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, China. Electronic address:

Herein, we report a method that combined "aptamer-locker" DNA with CRISPR/Cas12a-based biosensing for sensitive and rapid melamine analysis. Three strategies were harnessed for designing the DNA sensors that were well characterized by circular dichroism (CD) spectroscopy and isothermal titration calorimetry (ITC) in the absence and presence of melamine. The detection parameters were optimized to achieve good analytic performance. As a result, a limit of detection (LOD) as low as 38 nM was achieved, which is below the threshold (1.0 mg/kg) of allowable melamine in infant milk products. In addition, the sensors show high selectivity for melamine against other analogues such as cyanuric acid, ammeline and ammelide. Moreover, our method was effective for rapid melamine analysis in whole milk samples, with or without sample pretreatment, in less than 20 min. Adopting a commercially available portable fluorimeter, on-site analysis of melamine in milk was accomplished. The strategies demonstrated here can expand to detect other non-nucleic-acid targets by simply replacing the aptamers.
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http://dx.doi.org/10.1016/j.bios.2021.113233DOI Listing
July 2021

Highly In-Plane Anisotropic Two-Dimensional Ternary TaNiSe for Polarization-Sensitive Photodetectors.

ACS Appl Mater Interfaces 2021 Apr 9;13(15):17948-17956. Epub 2021 Apr 9.

Nanophotonics Research Center, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology & Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen 518060, China.

Intriguing anisotropic electrical and optoelectrical properties in two-dimensional (2D) materials are currently gaining increasing interest both for fundamental research and emerging optoelectronic devices. Identifying promising new 2D materials with low-symmetry structures will be rewarding in the development of polarization-integrated nanodevices. In this work, the anisotropic electron transport and optoelectrical properties of multilayer 2D ternary TaNiSe were systematically researched. The polarization-sensitive TaNiSe photodetector shows a linearly anisotropy ratio of ≈3.24 with 1064 nm illumination. The multilayer TaNiSe-based field-effective transistors exhibit an excellent field-effective mobility of 161.25 cm·V·s along the axis (armchair direction) as well as a great current saturation characteristic at room temperature. These results will promote a better understanding of the optoelectrical properties and applications in new categories of the in-plane anisotropic 2D materials.
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http://dx.doi.org/10.1021/acsami.1c00268DOI Listing
April 2021

Global burden of non-communicable diseases attributable to dietary risks in 1990-2019.

J Hum Nutr Diet 2021 Apr 9. Epub 2021 Apr 9.

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of ZheJiang University School of Medicine, Hangzhou, China.

Background: Dietary risks have raised attention worldwide during recent decades. The present burden-of-disease study aimed to evaluate the global dietary risks for non-communicable diseases (NCDs) from 1990 to 2019 and quantify their impact on mortality and disability-adjusted life-years (DALYs). Data from the 2019 Global Burden of Disease Study on deaths and DALYs from NCDs attributable to worldwide dietary risks were obtained and underwent deep analysis by year, age, gender, location, leading risks and leading causes, and their associations were examined. The socio-demographic index (SDI) was used as an indicator of national socio-economic status, as well as the relationships between age-standardised rates of deaths or DALYs and socio-economic status.

Results: In 2019, 7.9 million deaths and 187.7 million DALYs were attributable to dietary risk factors. High intake of sodium and low intake of whole grains and fruits were leading dietary risks for deaths and DALYs worldwide. However, both indices showed a decreasing trend by year, an increase by age and a higher disease burden in males. The main distribution of dietary-related NCDs was located in highly populated countries. A negative association between the SDI and disease burden and a positive association between the SDI and male preponderance were found.

Conclusions: Dietary risk factors for NCDs increased significantly and varied across regions during 1990-2019. Therefore, greater efforts are needed to raise public awareness of interventions and improve dietary practices aiming to reduce the disease burden caused by suboptimal dietary intake, especially in developing countries and among males.
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http://dx.doi.org/10.1111/jhn.12904DOI Listing
April 2021

Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor.

Front Oncol 2021 22;11:641166. Epub 2021 Mar 22.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

We report a rare subtype of adult cystic granulosa cell tumor (AGCT) characterized by elevated anti-Mullerian hormone and hyperandrogenism. A 35-year-old woman with primary infertility, hyperandrogenism, and irregular menses who was previously diagnosed with polycystic ovarian syndrome was diagnosed with AGCT based on histopathological examination and FOXL2 genetic test after laparoscopy. Due to fertility aspirations, she underwent controlled ovarian stimulation followed by embryo cryopreservation before salpingo-oophorectomy, and two embryos were frozen-thawed and transferred after surgery. A healthy female infant was delivered at 40 weeks' gestation. Cystic granulosa cell tumors should be considered a differential diagnosis in patients with persistent ovarian cysts and hyperandrogenism. Younger patients with AGCT with fertility goals should consider active assisted reproduction measures to preserve fertility before treatment for AGCT.
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http://dx.doi.org/10.3389/fonc.2021.641166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019939PMC
March 2021

Age-related changes in human conventional semen parameters and sperm chromatin structure assay-defined sperm DNA/chromatin integrity.

Reprod Biomed Online 2021 May 14;42(5):973-982. Epub 2021 Feb 14.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, China. Electronic address:

Research Question: What are the correlations between male age, traditional semen parameters, sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) in a sufficiently large sample size?

Design: Retrospective cohort study of 18,441 semen samples, with data divided into seven age groups according to male age: ≤25, 26-30, 31-35, 36-40, 41-45, 46-50 and ≥51 years.

Results: Age was negatively correlated with semen volume, total sperm count, motility and HDS, and positively correlated with sperm concentration and DFI (P < 0.001). After 35 years of age, semen volume and total sperm count began to decline. After 30 years of age, motility and HDS decreased consistently. Sperm concentration and DFI increased from 26-30 years of age. DFI was negatively correlated with sperm concentration, total sperm count, motility and normal morphology (P < 0.001) and positively correlated with semen volume and HDS (P < 0.001). HDS was negatively correlated with all parameters (P < 0.001) except semen volume (r = -0.013, P = 0.074) and DFI (r = 0.124, P < 0.001). Patients aged ≥40 years had higher DFI than those aged <40 years in the entire cohort, in the abnormal semen parameters cohort, and in the normal semen parameters cohort (OR 2.145, 2.042, 1.948, respectively, P < 0.001). The ≥40 years age group had a lower HDS than the <40 years age group in the entire cohort and abnormal semen parameters cohort (OR 0.719, 0.677, respectively, P < 0.001).

Conclusions: Ageing is a negative effector of sperm quantity and quality, and routine sperm parameters have weak but significant correlations with sperm DNA/chromatin integrity.
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http://dx.doi.org/10.1016/j.rbmo.2021.02.006DOI Listing
May 2021

Phenotypic and biochemical characteristics and molecular basis in 36 Chinese patients with androgen receptor variants.

Orphanet J Rare Dis 2021 03 9;16(1):122. Epub 2021 Mar 9.

Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Background: Androgen insensitive syndrome (AIS) is a rare genetic disease resulting from androgen receptor (AR) mutations and one of the causes of 46, XY disorder of sexual development (DSD). This study aimed to describe the clinical features and molecular defects of 36 Chinese patients with AR variants and investigate the functional alterations of novel variants in vitro.

Material And Methods: Subjects with AR variants were identified from 150 Chinese 46, XY DSD patients using targeted next-generation sequencing. In-silico and functional assays were performed to evaluate the transcriptional activity and nuclear localization of novel AR variants.

Results: Eight novel and fifteen reported AR variants were identified. 30.6% (11/36) of patients harbored additional variants other than AR. Mutations in the Arg841 residue were found in 7 unrelated patients. Postpubertal serum gonadotropin levels were significantly elevated in patients with complete AIS (CAIS) compared with those in patients with partial AIS (PAIS) (P < 0.05). All the novel variants initially predicted to be uncertain significance by in-silico analyses were reclassified as likely pathogenic for defective AR transcriptional activity in vitro, except p.L295P, which was found in an atypical patient with oligogenic mutations and reclassified as likely benign. c.368_369 ins T was observed to interfere with nuclear translocation.

Conclusions: Compared with PAIS patients, postpubertal CAIS patients had higher gonadotropin levels. Arg841 was disclosed as the location of recurrent mutations in Chinese AIS patients. Functional assays are important for reclassifying the novel AR variants and re-examining the diagnosis of AIS in specific patients with oligogenic mutations, instead of in-silico analysis.
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http://dx.doi.org/10.1186/s13023-021-01765-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942007PMC
March 2021

Poor intracytoplasmic sperm injection outcome in infertile males with azoospermia factor c microdeletions.

Fertil Steril 2021 Jul 19;116(1):96-104. Epub 2021 Mar 19.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, People's Republic of China; National Clinical Research Center for Obstetrics and Gynecology, Beijing, People's Republic of China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, People's Republic of China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, People's Republic of China.

Objective: To explore whether the presence of azoospermia factor c (AZFc) microdeletions adversely affects intracytoplasmic sperm injection (ICSI) outcome.

Design: Retrospective cohort.

Setting: University hospital.

Patient(s): A total of 293 patients with azoospermia or severe oligozoospermia AZFc deletions underwent 345 ICSI cycles, and 363 idiopathic patients with normal Y chromosome underwent 462 ICSI cycles.

Intervention(s): Testicular sperm aspiration, microdissection testicular sperm extraction.

Main Outcome Measure(s): The main clinical outcome parameters were cumulative clinical pregnancy rate, cumulative live birth delivery rate, and no embryo suitable for transfer cycle rate.

Result(s): Compared with the control group, the AZFc deletion group exhibited poorer ICSI outcome, with significant differences between the 2 groups for cumulative clinical pregnancy rate (45.39% vs. 67.49%; odds ratio [OR], 2.843; 95% confidence interval [CI]), cumulative live birth delivery rate (35.15% vs. 53.44%; OR, 2.234; 95% CI), no embryo suitable for transfer cycle rate (15.07% vs. 8.23%; OR, 0.565; 95% CI), fertilization rate (46.80% vs. 53.37%; adjusted β, -0.074; 95% CI), implantation rate (28.63% vs. 31.26%; adjusted β, -0.075; 95% CI) separately. The poor ICSI outcome of the AZFc deletion group was related to AZFc microdeletions by linear and logistic regression analyses.

Conclusion(s): AZFc microdeletions adversely affect ICSI outcome; patients with AZFc deletion should be informed that they have reduced opportunities to be biological fathers.
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http://dx.doi.org/10.1016/j.fertnstert.2021.01.025DOI Listing
July 2021

Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy.

Clin Transl Sci 2021 Mar 20. Epub 2021 Mar 20.

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening and difficult-to-treat organ-specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High-dose intravenous glucocorticoid (IVGC) therapy is considered a first-line treatment for active moderate-to-severe TAO, but there is still insufficient evidence regarding the treatment duration. Long-term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty-eight patients with active moderate-to-severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12-week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low-density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4-week group (p = 0.006). The change in the ADC was higher in the 4-week group than in the 12-week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4-week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.
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http://dx.doi.org/10.1111/cts.12999DOI Listing
March 2021

The impact of the gut microbiota on the reproductive and metabolic endocrine system.

Gut Microbes 2021 Jan-Dec;13(1):1-21

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman's lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.
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http://dx.doi.org/10.1080/19490976.2021.1894070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971312PMC
March 2021

Clinical application of an NGS-based method in the preimplantation genetic testing for Duchenne muscular dystrophy.

J Assist Reprod Genet 2021 Mar 15. Epub 2021 Mar 15.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 Hua Yuan Bei Road, Hai Dian District, Beijing, 100191, China.

Purpose: To determine whether next-generation sequencing (NGS) could be used to directly detect different mutations of Duchenne muscular dystrophy (DMD) during preimplantation genetic testing (PGT).

Methods: From Sep. 2016 to Aug. 2018, a total of six couples participated in this study. Four cases carried DMD exon deletions and two carried exon duplications. Trophectoderm cells were biopsied at day 5 or 6 and NGS was used in the genetic testing of the biopsied cells after whole-genome amplification. We developed a new method-DIRected Embryonic Cell Testing of Exon Deletion/Duplication (DIRECTED) to directly detect the single-gene mutation by NGS. Linage analysis based on single-nucleotide polymorphism (SNP) was used to validate the results from DIRECTED.

Results: In the four deletion cases, DIRECTED was used to detect DMD exon deletion in 16 biopsied embryos. All DIRECTED results were consistent with linkage analysis, indicating this method was reliable in detecting deletions around 1 Mb. In the two cases carrying exon duplications, no blastocyst was obtained for biopsy. Nonetheless, preliminary experiment results suggested that DIRECTED could also be used for direct detection of exon duplications in embryos.

Conclusions: Exon deletions or duplications in DMD of preimplantation embryos could be detected directly by NGS-based methods during PGT.
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http://dx.doi.org/10.1007/s10815-021-02126-zDOI Listing
March 2021

Untreated Prior Pulmonary Tuberculosis Adversely Affects Pregnancy Outcomes in Infertile Women Undergoing Fertilization and Embryo Transfer: A Large Retrospective Cohort Study.

Biomed Environ Sci 2021 Feb;34(2):130-138

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China;National Clinical Research Center for Obstetrics and Gynecology, Beijing 100191, China.

Objective: Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations before fertilization and embryo transfer (IVF-ET). It was unclear whether untreated PTB would affect pregnancy outcomes after IVF-ET.

Method: We conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups.

Results: The untreated PTB group had significantly lower clinical pregnancy (31.7% . 38.1%) and live birth (23.8% . 30.6%) rates than the non-PTB group (both < 0.001). Multivariate analysis revealed that untreated PTB was a risk factor for decreased live birth rate [odds ratio ( ), 0.80; 95% confidence interval ( ), 0.66-0.98; = 0.028] in all patients and for increased miscarriage ( , 4.19; 95% , 1.69-10.39; = 0.002) and decreased live birth ( , 0.45; 95% , 0.24-0.83; = 0.011) rates in patients with unexplained infertility.

Conclusions: Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.
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http://dx.doi.org/10.3967/bes2021.019DOI Listing
February 2021

Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex.

Cell Rep 2021 Mar;34(9):108788

Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, School of Life Sciences, Third Hospital, Peking University, Beijing 100871, China; Biomedical Pioneering Innovation Center and Center for Reproductive Medicine, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Chinese Institute for Brain Research, Beijing 100069, China; Center for Life Sciences, Beijing 100871, China. Electronic address:

The heterogeneity and molecular characteristics of progenitor cells, especially glial progenitors, in the developing human cerebral cortex remain elusive. Here, we find that EGFR expression begins to sharply increase after gestational week (GW) 20, which corresponds to the beginning stages of human gliogenesis. In addition, EGFR cells are mainly distributed in the germinal zone and frequently colocalize with the stemness marker SOX2 during this period. Then, by performing single-cell RNA sequencing on these EGFR cells, we successfully enriched and characterized various glial- and neuronal-lineage progenitor cells and validated their phenotypes in fixed slices. Notably, we identified two subgroups with molecular characteristics similar to those of astrocytes, and the immunostaining results show that these cells are mainly distributed in the outer subventricular zone and might originate from the outer radial glial cells. In short, the EGFR-sorting strategy and molecular signatures in the diverse lineages provide insights into human glial development.
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http://dx.doi.org/10.1016/j.celrep.2021.108788DOI Listing
March 2021

Fine mapping epitope on Glycoprotein-Gn from Severe Fever with Thrombocytopenia Syndrome Virus.

PLoS One 2021 2;16(3):e0248005. Epub 2021 Mar 2.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was recently identified as a tick-borne pathogen that threat to human health. Since 2010, many countries including China, South Korea, and Japan have reported Human SFTS caused by SFTSV infection. The glycoprotein encoded by the SFTSV M gene is the major antigenic component on the viral surface, and responsible for the viral entry, which makes it an important viral antigen and a clinical diagnostic target. The present study aimed to map linear B cell epitopes (BCEs) on the N-terminal glycoprotein (Gn) from SFTSV strain WCH/97/HN/China/2011 using the modified biosynthetic peptide method. Five fine epitopes (E1, 196FSQSEFPD203; E2, 232GHSHKII238; E3, 256VCYKEGTGPC265; E4, 285FCKVAG290, and E5, 316SYGGM320) were identified using the rabbit antisera. Western blot analysis showed that all the five epitopes interacted with the positive serum of sheep that had been naturally infected with SFTSV. Three-dimensional structural modeling analysis showed that all identified BCEs were located on the surface of the SFTSV-Gn and contained flexible loops. The sequence alignment revealed high conservation of the identified BCEs among 13 SFTSV strains from different lineage. These mapped epitopes will escalate the understanding of the epitope distribution and pathogenic mechanism of SFTSV, and could provide a basis for the development of a SFTSV multi-epitope detection antigen.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248005PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924767PMC
March 2021