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1.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3061-3070, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622617

RESUMO

The study of distinct genes, chromosomes and the spatio-temporal relationships between them is of great significance in genetics, developmental biology and biomedicine. CRISPR/Cas9 has become the most widely used gene editing tool due to its excellent targeting ability. Recently, researchers have developed a series of advanced live cell imaging techniques based on the nuclease-inactivated mutant of Cas9 (dCas9), providing rapid and convenient tools for high-resolution imaging of specific sites in the chromatin and genome. This review summarizes the advances of CRISPR/dCas9 system in live cell imaging from three aspects, including the strategies of cell delivery, optimization of the fluorescence signals, as well as orthogonal and multicolor imaging. Furthermore, we shed light on the development trends and prospects of this field.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Cromatina , Endonucleases
2.
Artigo em Inglês | MEDLINE | ID: mdl-34608573

RESUMO

PURPOSE: To study the application of next-generation sequencing on preimplantation genetic testing for recurrent hydatidiform mole patients. METHODS: A total of ten recurrent hydatidiform mole patients aged 27-34 years with a history of at least twice hydatidiform moles and no normal pregnancy were collected from 2019 to 2020. The diagnosis of hydatidiform mole type was clarified using short tandem repeat genotyping on products of conception, and whole-exome sequencing was applied for all patients and their partners. Seven recurrent hydatidiform mole patients with complete hydatidiform mole/partial hydatidiform mole type among previous hydatidiform mole tissues and no Pathogenetic/Likely pathogenetic/Uncertain significance variants in NLRP7/KHDC3L/MEI1/C11orf80 underwent a procedure of preimplantation genetic testing. Next-generation sequencing for analyzing the copy number variants and the numbers of heterozygous single nucleotide polymorphism was adopted to clarify the ploidy and parental origin of the embryo chromosomes in vitro. Embryos with biparental diploidy were selected for transfer. RESULTS: Seven patients have undergone the procedure of preimplantation genetic testing, and twenty-three embryos were obtained, among which 82.6% (n = 19) were identified transferrable and 17.4% (n = 4) were identified aneuploid. Two patients have delivered healthy babies and another is currently in the second trimester after transfer. CONCLUSION: Analyzing the copy number variants and the numbers of heterozygous single nucleotide polymorphism on the basis of next-generation sequencing can be utilized in the procedure of preimplantation genetic testing among part of recurrent hydatidiform mole patients. The current study is effective to reduce the occurrence of hydatidiform mole with improved clinical strategy, the advanced testing technology and analysis methods, as three of seven patients have conceived or delivered successfully.

3.
PLoS One ; 16(9): e0257248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507348

RESUMO

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis.

4.
Lancet ; 398(10304): 953-954, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509225
5.
JAMA Netw Open ; 4(9): e2123634, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34505887

RESUMO

Importance: Twin pregnancy is a common occurrence in pregnancies conceived with in vitro fertilization (IVF), but the absolute risk of adverse obstetric outcomes stratified by IVF, twin or singleton pregnancy, and maternal age are unknown. Objective: To estimate the absolute risk of adverse obstetric outcomes at each maternal age among twin pregnancies conceived with IVF. Design, Setting, and Participants: This retrospective cohort study included pregnant women with infants born from January 1, 2013, to December 31, 2018, based on the Hospital Quality Monitoring System in China. Data were analyzed from September 1, 2020, to June 30, 2021. Exposures: Twin pregnancy with IVF (IVF-T), singleton pregnancy with IVF (IVF-S), twin pregnancy with non-IVF (nIVF-T), and singleton pregnancy with non-IVF (nIVF-S). Main Outcomes and Measures: Sixteen obstetric outcomes, including 10 maternal complications (gestational hypertension, eclampsia and preeclampsia, gestational diabetes, placenta previa, placental abruption, placenta accreta, preterm birth, dystocia, cesarean delivery, and postpartum hemorrhage) and 6 neonatal complications (fetal growth restriction, low birth weight, very low birth weight, macrosomia, malformation, and stillbirth). Results: Among 16 879 728 pregnant women aged 20 to 49 years (mean [SD] age, 29.2 [4.7] years), the twin-pregnancy rates were 32.1% in the IVF group and 1.5% in the non-IVF group (relative risk, 20.8; 95% CI, 20.6-20.9). The most common adverse obstetric outcomes after pregnancy conceived with IVF were cesarean delivery (88.8%), low birth weight (43.8%), preterm birth (39.6%), gestational diabetes (20.5%), gestational hypertension and preeclampsia and eclampsia (17.5%), dystocia (16.8%), and postpartum hemorrhage (11.9%). The absolute risk of most adverse obstetric outcomes in each subgroup presented in 2 dominant patterns: Pattern A indicated the absolute risk ranging from IVF-T to nIVF-T to IVF-S to nIVF-S, and pattern B indicated the absolute risk ranging from IVF-T to IVF-S to nIVF-T to nIVF-S. Both patterns showed an elevated obstetric risk with increasing maternal age in each subgroup. Conclusions and Relevance: In this cohort study, twin pregnancy, IVF, and advanced maternal age were independently associated with adverse obstetric outcomes. Given these findings, promotion of the elective single embryo transfer strategy is needed to reduce multiple pregnancies following IVF technologies. Unnecessary cesarean delivery shouldh be avoided in all pregnant women.

6.
Biomed Res Int ; 2021: 2202888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513987

RESUMO

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.


Assuntos
Calpaína/genética , Hipertensão Pulmonar/genética , MicroRNAs/genética , Animais , Calpaína/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Hipertensão Pulmonar/patologia , Hipóxia/genética , Hipóxia/metabolismo , Masculino , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiologia , Ratos , Ratos Sprague-Dawley , Remodelação Vascular/genética
7.
Arch Gynecol Obstet ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410473

RESUMO

BACKGROUND: The pathophysiology of ovarian hyperstimulation syndrome (OHSS) is largely unknown. High ovarian response is acknowledged as a risk factor. However, in our clinical practice, the incidence of OHSS is not necessarily linked to the degree of such response among women. Here, we aimed to screen for potential risk factors other than those associated with ovarian response. METHODS: A total of 21,222 ovarian stimulation cycles were collected among women undergoing assisted reproductive technology, among which 84 patients with late-onset OHSS were identified as cases; corresponding matched control cases were obtained from the remaining 21,138 cycles. A multivariable logistic regression with the best subset method was performed to screen for significant risk factors. RESULTS: First, control samples were obtained with a case-to-control ratio of 1:4. The matching criteria were mainly ovarian response-related factors including age, body mass index, number of oocytes retrieved, standard or mild ovarian stimulation, and specific ovarian stimulation protocols. After matching the five ovarian response-related factors, 81 cases and 318 controls were obtained. The best model was selected after analysis as above. Basal serum low-density lipoprotein cholesterol (LDL-C), basal total cholesterol (TC), and estradiol (E2) concentrations on the day of triggering ovulation were included in the model, with odds ratios of 0.3410 (95% confidence interval, CI, 0.1618-0.7186), 2.2008 (95% CI 1.1192-4.3275) and 1.0000 (95% CI 1.0000-1.0001), respectively. CONCLUSION: Basal LDL-C was a risk factor negatively associated with late-onset OHSS, while basal TC and triggering E2 levels during ovarian stimulation were positive risk factors.

8.
Sci China Life Sci ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34302606

RESUMO

Early human embryogenesis is a very sophisticated process due to its unique gene regulatory network. Autophagy has been suggested to play an important role in mediating the development of early embryonic cells in mammals. However, evidence showing how autophagy regulates early human embryogenesis remains to be further explored. In this study, we systematically investigated the human transcriptome and methylome patterns of autophagy-related (ATG) genes in early embryonic cells at single-cell resolution. We analyzed the transcriptomic data of 365 cells and methylome data of 265 cells. The results showed that most ATG genes remained epigenetically active and were expressed stably throughout early embryogenesis, whereas the dynamics varied among different developmental stages. This evidence indicated that the autophagy pathway was constitutively activated and exerted a fundamental role in early human embryo development. Our work, for the first time, comprehensively reveals the features of autophagy during early human embryo development.

9.
Front Endocrinol (Lausanne) ; 12: 698579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305818

RESUMO

Several studies have reported the association between thyroid autoimmunity (TAI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes. However, the findings remain controversial. We performed a large-scale retrospective cohort study to verify the effect of the presence of thyroid antibodies on IVF/ICSI outcomes and fetal growth and to evaluate the association between the types and titers of thyroid antibodies and adverse IVF/ICSI outcomes. A total of 16481 patients with infertility were referred to the Reproductive Center of Peking University Third Hospital for their first IVF/ICSI treatment between January 2018 and June 2019.Patients who sought IVF/ICSI treatment due to tubal or male factors infertility and who achieved fresh embryo transfer were included in our study. Finally, 778 patients with thyroid antibody positivity were selected as the TAI group, and 778 age-matched patients were included in the control group. The number of oocytes retrieved and high-graded embryos and the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were compared between the TAI and control groups. In addition, subgroup analysis was performed to demonstrate whether different types and titers of thyroid antibodies had different effects on IVF/ICSI outcomes. After adjusting for thyroid function, anti-Müllerian hormone levels, basal follicle stimulating hormone levels, basal estradiol levels and antral follicle count, the number of oocytes retrieved in the TAI group was significantly lower than that in the control group. No significant differences were observed between the two groups in the rates of clinical pregnancy, miscarriage, preterm delivery, live birth, and birth weight in singletons; however, the birth weight in twin pregnancy was significantly lower in the TAI group than in the control group. Subgroup analysis showed no association between the types or titers of thyroid antibodies and adverse IVF/ICSI outcomes. In conclusion, the presence of TAI in patients with infertility did not impair embryo quality or affect pregnancy outcomes, including clinical pregnancy, miscarriage, preterm delivery, and live birth. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy.

10.
J Hazard Mater ; 421: 126685, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34332485

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are toxic and recalcitrant pollutants, with an urgent need for bioremediation. Systematic biodegradation studies show that surfactant-mediated bioremediation is still poorly understood. Here, we investigated a comprehensive cellular response pattern of the PAH degrading strain B. subtilis ZL09-26 to (non-)green surfactants at the cellular and proteomic levels. Eight characteristic cellular factor investigations and detailed quantitative proteomics analyses were performed to understand the highly enhanced phenanthrene (PHE) degradation efficiency (2.8- to 3-fold improvement) of ZL09-26 by humic acid (HA) or Tween80. The commonly upregulated pathway and proteins (Arginine generation, LacI-family transcriptional regulator, and Lactate dehydrogenase) and various metabolic pathways (such as phenanthrene degradation upstream pathway and central carbon metabolism) jointly govern the change of cellular behaviors and improvement of PHE transport, emulsification, and degradation in a network manner. The obtained molecular knowledge empowers engineers to expand the application of surfactants in the biodegradation of PAHs and other pollutants.

11.
Bioresour Technol ; 337: 125465, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34320745

RESUMO

Modificated lignins can affect enzymatic hydrolysis efficiency (EHE) because of changing physicochemical properties of lignin. In this study, carboxylated and quaternized lignin (CQL) and hydroxymethylated lignin (HML) were prepared to explore the effect of lignin modification on cellulase adsorption and EHE of p-toluenesulfonic acid treated corn stover (PCS). The results showed that CQL enhanced EHE of PCS due to the higher ß-glucosidase (ß-GL) activity, resulting from the formation of CQL-ß-GL complexes with a lower binding free energy and the improvement of ß-GL conformation made by the binding of CQL and ß-GL. However, the drop in EHE due to the addition of HML was consequent on ß-GL deactivation that was because the binding site of HML and ß-GL overlapped with the carbohydrate binding domain of ß-GL, causing the decrease in ß-GL activity compared with CQL. This study would help deeply elucidate the effect of modified lignins on EHE and cellulase adsorption.


Assuntos
Celulase , Lignina , Adsorção , Benzenossulfonatos , Hidrólise
12.
Eur J Obstet Gynecol Reprod Biol ; 262: 216-220, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34062308

RESUMO

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.


Assuntos
Infertilidade Masculina , Infertilidade , China , Feminino , Humanos , Inseminação , Inseminação Artificial , Letrozol , Masculino , Indução da Ovulação , Projetos Piloto , Gravidez , Taxa de Gravidez
13.
J Clin Invest ; 131(12)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34128477

RESUMO

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.


Assuntos
Blastocisto/metabolismo , Ácidos Nucleicos Livres/metabolismo , Metilação de DNA , Aneuploidia , Blastocisto/patologia , Ácidos Nucleicos Livres/genética , Meios de Cultura , Técnicas de Cultura Embrionária , Estudo de Associação Genômica Ampla , Humanos
14.
Hum Reprod ; 36(9): 2452-2462, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34179971

RESUMO

STUDY QUESTION: Is ovarian stimulation with follitropin delta in its individualised fixed-dose regimen at least as efficacious as follitropin alfa in a conventional dosing regimen in Asian population? SUMMARY ANSWER: Ovarian stimulation with individualised follitropin delta dosing resulted in a non-inferior ongoing pregnancy rate, a significantly higher live birth rate and a significantly lower incidence of early ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions compared to conventional follitropin alfa dosing. WHAT IS KNOWN ALREADY: Previous randomised controlled trials conducted in Japan as well as in Europe, North- and South America have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum anti-Müllerian hormone (AMH) level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates. STUDY DESIGN, SIZE, DURATION: Randomised, controlled, multi-centre, assessor-blind trial conducted in 1009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle. Randomisation was stratified by age (<35, 35-37, 38-40 years). The primary endpoint was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority limit -10.0%; analysis adjusted for age stratum). PARTICIPANTS/MATERIALS, SETTING, METHODS: The follitropin delta treatment consisted of a fixed daily dose individualised according to each patient's initial AMH level and body weight (AMH <15 pmol/l: 12 µg; AMH ≥15 pmol/l: 0.19 to 0.10 µg/kg; min-max 6-12 µg). The follitropin alfa dose was 150 IU/day for the first 5 days with subsequent potential dose adjustments according to individual response. A GnRH antagonist protocol was applied. OHSS was classified based on Golan's system. Women with an ongoing pregnancy were followed until live birth and 4 weeks after. MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes retrieved was significantly (P < 0.001) lower with individualised follitropin delta versus conventional follitropin alfa (10.0 ± 6.1 versus 12.4 ± 7.3). Nevertheless, compared to the conventional dosing approach, the individualised follitropin delta dosing regimen resulted in on average 2 more oocytes (9.6 ± 5.3 versus 7.6 ± 3.5) in potential low responders as indicated by AMH <15 pmol/l, and on average 3 fewer oocytes (10.1 ± 6.3 versus 13.8 ± 7.5) in potential high responders as indicated by AMH ≥15 pmol/l. Among women with AMH ≥15 pmol/l, excessive response occurred less frequently with individualised follitropin delta than with follitropin alfa (≥15 oocytes: 20.2% versus 39.1%; ≥20 oocytes: 6.7% versus 18.5%; both P < 0.001). The incidence of early OHSS and/or preventive interventions for early OHSS was significantly (P = 0.004) reduced from 9.6% with follitropin alfa to 5.0% with individualised follitropin delta. The total gonadotropin use was significantly (P < 0.001) reduced from an average of 109.9 ± 32.9 µg (1498 ± 448 IU) follitropin alfa to 77.5 ± 24.4 µg follitropin delta. Non-inferiority of follitropin delta in its individualised dosing regimen to conventional follitropin alfa was established with respect to the primary endpoint of ongoing pregnancy rate which was 31.3% with follitropin delta compared to 25.7% with follitropin alfa (estimated mean difference 5.4% [95% CI: -0.2%; 11.0%]). The live birth rate was significantly higher at 31.3% with individualised follitropin delta compared to 24.7% with follitropin alfa (estimated mean difference 6.4% [95% CI: 0.9%; 11.9%]; P = 0.023). The live birth rate for each stratum were as follows for follitropin delta and follitropin alfa, respectively; <35 years: 31.0% versus 25.0%, 35-37 years: 35.3% versus 26.7%, 38-40 years: 20.0% versus 14.3%. LIMITATIONS, REASONS FOR CAUTION: The trial only covered the clinical outcome of one treatment cycle with fresh cleavage-stage embryo transfers. WIDER IMPLICATIONS OF THE FINDINGS: The present trial shows that in addition to reducing the early OHSS risk, follitropin delta in its individualised fixed-dose regimen has the potential to improve the success rate in fresh cycles across all ages and with a lower gonadotropin consumption compared to conventional follitropin alfa dosing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Ferring Pharmaceuticals. J.Q., Y.Z., X.L., T.H., H.-Y.H. and S.-H.K. have received institutional (not personal) clinical trial fees from Ferring Pharmaceuticals. M.G., B.M. and J.-C.A. are employees of Ferring Pharmaceuticals. J.-C.A. has pending and issued patent applications in the WO 2013/020996 and WO 2019/043143 patent families that comprise allowed and granted patent rights related to follitropin delta. TRIAL REGISTRATION NUMBER: NCT03296527 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 28 September 2017. DATE OF FIRST PATIENT'S ENROLMENT: 1 December 2017.


Assuntos
Fertilização In Vitro , Injeções de Esperma Intracitoplásmicas , Adulto , Feminino , Hormônio Foliculoestimulante Humano , Humanos , Indução da Ovulação , Gravidez , Taxa de Gravidez , Proteínas Recombinantes
15.
Pediatr Infect Dis J ; 40(7): 663-668, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34097659

RESUMO

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.

16.
Reprod Biol Endocrinol ; 19(1): 82, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088310

RESUMO

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.

17.
Brief Bioinform ; 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34097004

RESUMO

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.

18.
Chin Med J (Engl) ; 134(12): 1405-1415, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091521

RESUMO

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 ±â€Š4.05 vs. 33.09 ±â€Š5.13, P < 0.001). The average duration of infertility was shorter than the non-live birth cohort (4.22 ±â€Š3.11 vs. 5.06 ±â€Š4.08, 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 ±â€Š7.98 vs. 11.35 ±â€Š7.60, P < 0.001; 6.66 ±â€Š5.19 vs. 3.62 ±â€Š3.51, 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.


Assuntos
Coeficiente de Natalidade , Injeções de Esperma Intracitoplásmicas , China , Feminino , Fertilização In Vitro , Humanos , Nascido Vivo , Indução da Ovulação , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
19.
Front Endocrinol (Lausanne) ; 12: 667422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122341

RESUMO

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.

20.
J Assist Reprod Genet ; 38(9): 2425-2434, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33939064

RESUMO

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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