Effects of ovarian stimulation on embryo euploidy: an analysis of 12 874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: Does ovarian stimulation and the ovarian response affect embryo euploidy? SUMMARY ANSWER: Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. WHAT IS KNOWN ALREADY: Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. STUDY DESIGN SIZE DURATION: A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). MAIN RESULTS AND THE ROLE OF CHANCE: Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). LIMITATIONS REASONS FOR CAUTION: Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

How the extra X chromosome impairs the development of male fetal germ cells.

The dosage of X-linked genes is accurately regulated with the development of fetal germ cells (FGCs)1,2. How aberrant dosage of X-linked genes impairs FGC development in humans remains poorly understood. FGCs of patients with Klinefelter syndrome (KS), who have an extra X chromosome, provide natural models for addressing this issue3. Here we demonstrate that most human FGCs in KS are arrested at an early stage, characterized by the upregulation of genes related to pluripotency, the WNT pathway and the TGF-ß pathway, along with the downregulation of genes involved in FGC differentiation. The limited KS FGCs that are capable of reaching the late stage remain relatively naive. X chromosomes are not inactivated and the dosage of X-linked genes is excessive in KS FGCs. X-linked genes dominate the differentially expressed genes and are enriched in critical biological processes associated with the developmental delay of KS FGCs. Moreover, aberrant interactions between Sertoli cells and FGCs disrupt the migration of late FGCs to the basement membrane in KS. Notably, inhibition of the TGF-ß pathway improves the differentiation of KS FGCs. Our findings elucidate how the extra X chromosome impairs the development of male FGCs and reveal the initial molecular events preceding germ cell loss in KS.

Sex differences in human pre-gastrulation embryos.

Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment, yet their origins and underlying mechanisms remain uncertain. Here, we conduct a detailed investigation of sex differences in human pre-gastrulation embryos. The lower methylation and incomplete inactivation of the X chromosome in females, as well as the sex-specific cell-cell communication patterns, contribute to sex-differential transcription. Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity, while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals. Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females. The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females, while the situation is opposite in the trophectoderm. In conclusion, our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.

Human embryos harbor complex mosaicism with broad presence of aneuploid cells during early development.

Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained 'chromosome-complementary' cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8-14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.

Single nucleotide polymorphisms in SEPALLATA 2 underlie fruit length variation in cucurbits.

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single-nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found 2 SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of 4 near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resulting in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

[Genetic analysis of carriers of complex chromosome rearrangement].

OBJECTIVE: To comprehensively analyze the numbers of involved chromosomes and breakpoints and the clinical phenotypes of the patients with complex chromosome rearrangement (CCR). METHODS: We selected 23 745 patients with abnormal fertility seeking medical care in the Center of Reproductive Medicine of Peking University Third Hospital from 2011 to 2015, and analyzed their peripheral blood chromosomal karyotypes using G-banding, C-banding and fluorescence in situ hybridization (FISH). RESULTS: A total of 28 CCR carriers (0.118%) were detected among the 23 745 patients with abnormal fertility, including 18 males mainly with azoospermia or oligoasthenospermia and 10 females mainly with infertility, recurrent abortion, embryo termination and abnormal birth. Of the 28 cases of CCR, tripartite rearrangement was found in 9 (32.14%), double translocation in 7 (25%) and special translocation in 12 (42.86%). CCR carrier-related chromosomes were all involved but chromosomes 12 and 19, while 2 and 5 were involved most frequently. CONCLUSION: At present, the incidence of CCR is low. CCR carriers with normal phenotypes are often found because of reproductive problems, and their low chance of having a normal baby necessitates the use of preimplantation genetic test to improve the rate of live birth. Due to the diversity of the chromosomes and breakpoints involved in CCR, it is crucial to give each CCR carrier precise genetic counseling.

Assessing the necessity of screening ≤5 Mb segmental aneuploidy in routine PGT for aneuploidies.

RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.

Characterization of Two Novel Single-Stranded RNA Viruses from Agroathelia rolfsii, the Causal Agent of Peanut Stem Rot.

Peanut stem rot is a soil-borne disease caused by Agroathelia rolfsii. It occurs widely and seriously affects the peanut yield in most peanut-producing areas. The mycoviruses that induce the hypovirulence of some plant pathogenic fungi are potential resources for the biological control of fungal diseases in plants. Thus far, few mycoviruses have been found in A. rolfsii. In this study, two mitoviruses, namely, Agroathelia rolfsii mitovirus 1 (ArMV1) and Agroathelia rolfsii mitovirus 2 (ArMV2), were identified from the weakly virulent A. rolfsii strain GP3-1, and they were also found in other A. rolfsii isolates. High amounts of ArMV1 and ArMV2in the mycelium could reduce the virulence of A. rolfsii strains. This is the first report on the existence of mitoviruses in A. rolfsii. The results of this study may provide insights into the classification and evolution of mitoviruses in A. rolfsii and enable the exploration of the use of mycoviruses as biocontrol agents for the control of peanut stem rot.

GametesOmics: A Comprehensive Multi-omics Database for Exploring the Gametogenesis in Humans and Mice.

Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we develop GametesOmics, a comprehensive database that integrates the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification(s) of each gene; Tools with Differentially expressed gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression, DNA methylation, and chromatin accessibility between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.

Concurrent Preimplantation Genetic Testing and Competence Assessment of Human Embryos by Transcriptome Sequencing.

Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.

Outcomes and the effect of PGT-M in women with hormone-related hereditary tumor syndrome.

Purpose: To review the outcome of PGT-M in hormone-related hereditary tumor syndrome and evaluate the effect of ovarian induction on tumor growth in those patients. Methods: Medical records of PGT-M were retrospectively analyzed in patients with hormone-related heritage tumors in our reproductive center. A total of eleven women with hereditary breast and ovarian cancer (HBOC) (including BRCA1/2 mutation carriers), and Lynch syndrome (including MMR gene mutation carriers) were included. Thirteen IVF/PGT-M cycles were performed. Eleven for PGT-M and two for fertility preservation. The ovulation protocol, numbers of oocytes retrieved and two pronuclei (2PN) zygotes, PGT-M results, and clinical outcomes were analyzed. Tumor progression was also estimated by comparing transvaginal ultrasound (TVS), MR, CT, or colonoscopy according to the follow-up requirements of different tumors. Results: Eleven IVF/PGT-M cycles were performed with an antagonist protocol; Two cycles were performed with a mild stimulation protocol. The total dose of gonadotropin (Gn) was 1827 IU per patient (range from 1200 to 2625 IU). The median number of oocytes retrieved was 13 (range from 4 to 30), and the median number of 2PN zygotes was 8 (range from 2 to 16). A total of 32 embryos underwent PGT-M, and 9 (28.1%) embryos were suitable for transfer. Six transfer cycles were performed, and 5 cycles got clinical pregnancy (83%) with five newborns (83%). The follow-up examinations conducted 10-18 months after PGT-M/delivery revealed no new lesions or tumor progression. Conclusion: PGT-M results can provide important information for improving the consultation of hormone-related heritage tumor patients regarding their fertility preservation and reproductive options. Ovarian induction for women with hormone-related hereditary tumor syndrome is not associated with tumor progression.

Diverse impacts of female chromosomal polymorphisms on assisted reproduction outcomes: a retrospective cohort study.

BACKGROUND: The effects of female chromosomal polymorphisms (FCPs) on various aspects of reproductive health have been investigated, yet the findings are frequently inconsistent. This study aims to clarify the role of FCPs on the outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: This retrospective cohort study comprised 951 couples with FCPs and 10,788 couples with normal karyotypes who underwent IVF/ICSI treatment at Peking University Third Hospital between 2015 and 2021. The exposure was FCPs. The embryological outcomes and clinical outcomes were compared. RESULTS: The FCPs, as a whole, compromised the oocyte maturation rate (76.0% vs. 78.8%, P = 0.008), while they did not adversely affect other IVF/ICSI outcomes. Further detailed analyses showed that every type of FCPs contributed to the lower oocyte maturation rate, particularly the rare FCPs (69.0% vs. 78.8%, P = 0.008). The female qh + was associated with a higher normal fertilization rate (63.0% vs. 59.2%, adjusted P = 0.022), a higher clinical pregnancy rate (37.0% vs. 30.7%, adjusted P = 0.048), and a higher live birth rate (27.0% vs.19.0%, adjusted P = 0.003) in couples undergoing IVF. Conversely, in couples undergoing ICSI, female qh + was found to be related to a lower normal fertilization rate (58.8% vs. 63.8%, P = 0.032), a comparable clinical pregnancy rate (25.7% vs. 30.9%, P = 0.289), and a comparable live birth rate (19.8% vs. 19.2%, P = 0.880) compared to the control group. Additionally, an increased risk of preterm birth was observed in women undergoing IVF with multiple polymorphisms (62.5% vs. 16.9%, adjusted P <  0.001) and in women undergoing ICSI with pstk+ (36.4% vs. 15.4%, P = 0.036). CONCLUSIONS: Our research unravels the diverse impacts of various FCPs on IVF/ICSI outcomes, highlighting the detrimental effects of FCPs on oocyte maturation and the risk of preterm birth.

A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming.

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.

Genome-Wide Analysis of Trehalose-6-Phosphate Phosphatase Gene Family and Their Expression Profiles in Response to Abiotic Stress in Groundnut.

Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme in trehalose biosynthesis which plays an essential role in plant development and in the abiotic stress response. However, little is currently known about TPPs in groundnut. In the present study, a total of 16 AhTPP genes were identified, and can be divided into three phylogenetic subgroups. AhTPP members within the same subgroups generally displayed similar exon-intron structures and conserved motifs. Gene collinearity analysis revealed that segmental duplication was the primary factor driving the expansion of the AhTPP family. An analysis of the upstream promoter region of AhTPPs revealed eight hormone- and four stress-related responsive cis-elements. Transcriptomic analysis indicated high expression levels of AhTPP genes in roots or flowers, while RT-qPCR analysis showed upregulation of the six tested genes under different abiotic stresses, suggesting that AhTPPs play roles in growth, development, and response to various abiotic stresses. Subcellular localization analysis showed that AhTPP1A and AhTPP5A were likely located in both the cytoplasm and the nucleus. To further confirm their functions, the genes AhTPP1A and AhTPP5A were individually integrated into yeast expression vectors. Subsequent experiments demonstrated that yeast cells overexpressing these genes displayed increased tolerance to osmotic and salt stress compared to the control group. This study will not only lay the foundation for further study of AhTPP gene functions, but will also provide valuable gene resources for improving abiotic stress tolerance in groundnut and other crops.

Development of a novel DGT passive sampler for measuring polycyclic aromatic hydrocarbons in aquatic systems.

Polycyclic aromatic hydrocarbons (PAHs) are priority pollutants and need to be measured reliably in waters and other media, to understand their sources, fate, behaviour and to meet regulatory monitoring requirements. Conventional water sampling requires large water volumes, time-consuming pre-concentration and clean-up and is prone to analyte loss or contamination. Here, for the first time, we developed and validated a novel diffusive gradients in thin-films (DGT) passive sampler for PAHs. Based on the well-known DGT principles, the sampler pre-concentrates PAHs with typical deployment times of days/weeks, with minimal sample handling. For the first time, DGT holding devices made of metal and suitable for sampling hydrophobic organic compounds were designed and tested. They minimize sorption and sampling lag times. Following tests on different binding layer resins, a MIP-DGT was preferred - the first time applying MIP for PAHs. It samples PAHs independent of pH (3.9 -8.1), ionic strength (0.01 -0.5 M) and dissolved organic matter < 20 mg L-1, making it suitable for applications across a wide range of environments. Field trials in river water and wastewater demonstrated that DGT is a convenient and reliable tool for monitoring labile PAHs, readily achieving quantitative detection of environmental levels (sub-ng and ng/L range) when coupled with conventional GC-MS or HPLC. ENVIRONMENTAL IMPLICATIONS: PAHs are carcinogenic and genotoxic compounds. They are environmentally ubiquitous and must be monitored in waters and other media. This study successfully developed a new DGT passive sampler for reliable in situ time-integrated measurements of PAHs in waters at the ng/L level. This is the first time to use passive samplers for accurate measurements of hydrophobic organic contaminants in aquatic systems without calibration, a big step forward in monitoring PAHs. The application of this new sampler will enhance our understanding of the sources, fate, behavior and ecotoxicology of PAHs, enabling improved environmental risk assessment and management of these compounds.

Impacts of male chromosomal polymorphisms on semen quality and IVF/ICSI outcomes: A retrospective cohort study.

OBJECTIVE: The study aims to elucidate the impacts of different types of male chromosomal polymorphisms (MCPs) on various outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. METHODS: This retrospective cohort study included 1442 couples with normal karyotypes, 1442 couples with MCPs, 42 couples with male chromosomal rearrangements (MCRs), and 42 couples with MCRs combined with MCPs who underwent IVF/ICSI treatment at Peking University Third Hospital from 2015 to 2021. The semen quality, embryological outcomes, and clinical outcomes of different groups stratified by karyotypes were compared. RESULTS: For couples undergoing IVF, male inv(9) was associated with a significantly lower sperm viability rate (29.41% vs 34.49%, P = 0.030), a lower progressive motility rate (25.13% vs 30.50%, P = 0.013), and a lower normal fertilization rate (52.41% vs 59.84%, P = 0.014). Male 9qh + was related to a lower sperm viability rate (27.56% vs 34.49%, P = 0.028). No MCPs were observed to compromise clinical outcomes in couples undergoing IVF. For couples undergoing ICSI, no MCPs exhibited an association with poorer semen quality and embryological outcomes. However, Yqh + and DGpstk+ were found to be significantly correlated with an increased likelihood of preterm birth (23.3% vs 9.2%, P = 0.003; 20.0% vs 9.2%, P = 0.041, respectively). In couples with MCRs, the presence of MCPs significantly reduced the sperm viability rate (19.99% vs 30.97%, P = 0.017) and progressive motility rate (8.07% vs 27.85%, P = 0.018). CONCLUSION: Our study provides detailed evidence for the impacts of various MCPs on IVF/ICSI outcomes, reveals the complexity and heterogeneity of these impacts, and highlights the adverse effects of male inv(9).

Pain Characteristics and Progression to Sarcopenia in Chinese Middle-Aged and Older Adults: A 4-Year Longitudinal Study.

BACKGROUND: It is imperative for public health to identify the factors that contribute to the progression of sarcopenia among middle-aged and older adults. Our study aimed to investigate the association between pain characteristics and the progression to sarcopenia and its subcomponents among middle-aged and older adults in China. METHODS: We included 5 568 participants from the China Health and Retirement Longitudinal Study. All participants completed assessments for pain characteristics and sarcopenia. Pain assessment included pain status (baseline pain, incident pain, and pain persistence) and pain distribution (single-site pain and multisite pain) using a self-report questionnaire. Diagnosis of sarcopenia followed The Asian Working Group for Sarcopenia 2019 consensus. The odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by logical regression analysis. RESULTS: Participants who reported baseline pain, multisite pain, pain persistence, or multisite pain persistence were more likely to progress to sarcopenia than those without pain, with ORs of 1.33 (95% CI: 1.08-1.65), 1.44 (95% CI: 1.15-1.80), 1.63 (95% CI: 1.23-2.14), and 1.59 (95% CI: 1.19-2.11), respectively. Even after adjusting for other covariates such as gender, age, residential area, education level, marital status, smoking, alcohol consumption, comorbidities, and falls, these associations remained significant. Additionally, pain persistence and multisite pain persistence were significantly associated with low grip strength and clinically meaningful Short Physical Performance Battery decline, but not with low muscle mass. CONCLUSIONS: Our study showed that pain, especially pain persistence, was closely correlated to the increased risk of progression to sarcopenia in Chinese middle-aged and older adults.

Full-length transcriptome sequencing provides insights into alternative splicing under cold stress in peanut.

Introduction: Peanut (Arachis hypogaea L.), also called groundnut is an important oil and cash crop grown widely in the world. The annual global production of groundnuts has increased to approximately 50 million tons, which provides a rich source of vegetable oils and proteins for humans. Low temperature (non-freezing) is one of the major factors restricting peanut growth, yield, and geographic distribution. Since the complexity of cold-resistance trait, the molecular mechanism of cold tolerance and related gene networks were largely unknown in peanut. Methods: In this study, comparative transcriptomic analysis of two peanut cultivars (SLH vs. ZH12) with differential cold tolerance under low temperature (10°C) was performed using Oxford Nanopore Technology (ONT) platform. Results and discussion: As a result, we identified 8,949 novel gene loci and 95,291 new/novel isoforms compared with the reference database. More differentially expressed genes (DEGs) were discovered in cold-sensitive cultivar (ZH12) than cold-tolerant cultivar (SLH), while more alternative splicing events were found in SLH compared to ZH12. Gene Ontology (GO) analyses of the common DEGs showed that the "response to stress", "chloroplast part", and "transcription factor activity" were the most enriched GO terms, indicating that photosynthesis process and transcription factors play crucial roles in cold stress response in peanut. We also detected a total of 708 differential alternative splicing genes (DASGs) under cold stress compared to normal condition. Intron retention (IR) and exon skipping (ES) were the most prevalent alternative splicing (AS) events. In total, 4,993 transcription factors and 292 splicing factors were detected, many of them had differential expression levels and/or underwent AS events in response to cold stress. Overexpression of two candidate genes (encoding trehalose-6-phosphatephosphatases, AhTPPs) in yeast improves cold tolerance. This study not only provides valuable resources for the study of cold resistance in peanut but also lay a foundation for genetic modification of cold regulators to enhance stress tolerance in crops.

Stress biomarkers and child development in young children in Bangladesh.

BACKGROUND: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. METHODS: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. RESULTS: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. CONCLUSIONS: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.