Stability of the cytosine methylome during post-testicular sperm maturation in mouse.

Beyond the haploid genome, mammalian sperm carry a payload of epigenetic information with the potential to modulate offspring phenotypes. Recent studies show that the small RNA repertoire of sperm is remodeled during post-testicular maturation in the epididymis. Epididymal maturation has also been linked to changes in the sperm methylome, suggesting that the epididymis might play a broader role in shaping the sperm epigenome. Here, we characterize the genome-wide methylation landscape in seven germ cell populations from throughout the male reproductive tract. We find very few changes in the cytosine methylation landscape between testicular germ cell populations and cauda epididymal sperm, demonstrating that the sperm methylome is stable throughout post-testicular maturation. Although our sequencing data suggested that caput epididymal sperm exhibit a highly unusual methylome, follow-up studies revealed that this resulted from contamination of caput sperm by extracellular DNA. Extracellular DNA formed web-like structures that ensnared sperm, and was present only in sperm samples obtained from the caput epididymis and vas deferens of virgin males. Curiously, contaminating extracellular DNA was associated with citrullinated histone H3, potentially resulting from a PAD-driven genome decondensation process. Taken together, our data emphasize the stability of cytosine methylation in mammalian sperm, and identify a surprising, albeit transient, period during which sperm are associated with extracellular DNA.

New allele of mouse DNA/RNA helicase senataxin causes meiotic arrest and infertility.

In brief: A new allele of the senataxin gene Setxspcar3 causes meiotic arrest of spermatocytes with aberrant DNA damage and accumulation of R-loops. Abstract: An unbiased screen for discovering novel mouse genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. The Setxspcar3 mutant mice exhibit male infertility and female subfertility. Histology of the Setxspcar3 mutant testes revealed the absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, defective formation of the sex body, and arrest of meiosis in mid-prophase. Additionally, Setxspcar3 testicular cells exhibit abnormal accumulation of R-loops. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for the determination of its role in maintaining R-loop formation and genome integrity.

Linking hydraulic geometry, land use, and stream water quality in the Taihu Basin, China.

Understanding the complexity of catchment-scale human activities, natural factors, and stream water quality is particularly important for basin water resources management. Thorough investigations on how multiple environmental factors quantitatively and simultaneously affect water quality are limited. This study employed Spearman's correlation and ridge regression analysis (RRA) to disentangle the hydraulic geometry and land use contributions to water quality variables (WQVs). Nine and six indicators were used to describe the hydraulic geometry and land use characteristics, respectively, in the Taihu Basin. The results revealed significant correlations between the land use, hydraulic geometry, and stream water quality. Built-up land and cropland negatively impacted the stream water quality, while woodland had the opposite trend. The structure and morphological connectivity of the river network were associated with most WQVs. The hydrologic connectivity characteristics strongly influenced ammonia-nitrogen (NH3-N), permanganate index (CODMn), and dissolved oxygen (DO). Six equations that estimated the stream water quality were established through RRA. Human factors impose a greater impact on the stream water quality than natural factors in the Taihu Basin. Our findings provide quantitative insights to mitigate water pollution via reasonable management and control of the river structure and connectivity and land-use patterns.

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes.

SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre-driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females.

The Association Between the rs2975760 and rs3792267 Single Nucleotide Polymorphisms of Calpain 10 (CAPN10) and Gestational Diabetes Mellitus.

BACKGROUND This study aimed to investigate the association between the rs2975760 and rs3792267 single nucleotide polymorphisms (SNPs) of the calpain 10 (CAPN10) gene and gestational diabetes mellitus. MATERIAL AND METHODS The study included 138 patients with gestational diabetes mellitus and 152 healthy pregnant women. Venous blood was separated, and the DNA was extracted. The rs2975760 and rs3792267SNP polymorphisms of CAPN10 were detected using polymerase chain reaction (PCR). The frequencies of different genotypes in patients with gestational diabetes mellitus and healthy pregnant women were determined, and the relationship between different SNP genotypes and the risk of gestational diabetes mellitus was analyzed. RESULTS There were no significant differences in the frequencies of the TT, CT and CC genotypes of rs2975760 and the frequencies of the GG, AG and AA genotypes of rs3792267 between the women with gestational diabetes and the controls. Expression of rs2975760 and rs3792267 were not associated with the risk of gestational diabetes in the dominant model, recessive model, and additive model. However, grade B and grade D diabetes in the CC and TC genotypes of rs2975760 were significantly different from those in the TT genotype (P<0.05). Grade B and grade D diabetes in the AA and AG genotypes of rs3792267 were significantly different compared with those in the GG genotype (P<0.05), and allele A was significantly increased compared with allele G (P<0.05). CONCLUSIONS The rs2975760 and rs3792267 SNP polymorphisms of CAPN10 showed no significant association with the incidence of gestational diabetes mellitus and only a mild association with the severity.

Nuclear localization of EIF4G3 suggests a role for the XY body in translational regulation during spermatogenesis in mice.

Eukaryotic translation initiation factor 4G (EIF4G) is an important scaffold protein in the translation initiation complex. In mice, mutation of the Eif4g3 gene causes male infertility, with arrest of meiosis at the end of meiotic prophase. This study documents features of the developmental expression and subcellular localization of EIF4G3 that might contribute to its highly specific role in meiosis and spermatogenesis. Quite unexpectedly, EIF4G3 is located in the nucleus of spermatocytes, where it is highly enriched in the XY body, the chromatin domain formed by the transcriptionally inactive sex chromosomes. Moreover, many other, but not all, translation-related proteins are also localized in the XY body. These unanticipated observations implicate roles for the XY body in controlling mRNA metabolism and/or "poising" protein translation complexes before the meiotic division phase in spermatocytes.

Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.

BACKGROUND: The continuous and non-synchronous nature of postnatal male germ-cell development has impeded stage-specific resolution of molecular events of mammalian meiotic prophase in the testis. Here the juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis that allows decomposition of the transcriptional programs of spermatogonia and meiotic prophase substages. RESULTS: Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), prepared as surface-spread chromatin and immunolabeled for meiotic stage-specific protein markers (STRA8, SYCP3, phosphorylated H2AFX, and HISTH1T). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. Independent principal component analyses of cytological and transcriptomic data yielded similar patterns for both data types, providing strong evidence for substage-specific gene expression signatures. A novel permutation-based maximum covariance analysis (PMCA) was developed to map co-expressed transcripts to one or more of the eight meiotic prophase substages, thereby linking distinct molecular programs to cytologically defined cell states. Expression of meiosis-specific genes is not substage-limited, suggesting regulation of substage transitions at other levels. CONCLUSIONS: This integrated analysis provides a general method for resolving complex cell populations. Here it revealed not only features of meiotic substage-specific gene expression, but also a network of substage-specific transcription factors and relationships to potential target genes.

Nuclear localization of PRDM9 and its role in meiotic chromatin modifications and homologous synapsis.

Developmental progress of germ cells through meiotic phases is closely tied to ongoing meiotic recombination. In mammals, recombination preferentially occurs in genomic regions known as hotspots; the protein that activates these hotspots is PRDM9, containing a genetically variable zinc finger (ZNF) domain and a PR-SET domain with histone H3K4 trimethyltransferase activity. PRDM9 is required for fertility in mice, but little is known about its localization and developmental dynamics. Application of spermatogenic stage-specific markers demonstrates that PRDM9 accumulates in male germ cell nuclei at pre-leptonema to early leptonema but is no longer detectable in nuclei by late zygonema. By the pachytene stage, PRDM9-dependent histone H3K4 trimethyl marks on hotspots also disappear. PRDM9 localizes to nuclei concurrently with the deposition of meiotic cohesin complexes, but is not required for incorporation of cohesin complex proteins into chromosomal axial elements, or accumulation of normal numbers of RAD51 foci on meiotic chromatin by late zygonema. Germ cells lacking PRDM9 exhibit inefficient homology recognition and synapsis, with aberrant repair of meiotic DNA double-strand breaks and transcriptional abnormalities characteristic of meiotic silencing of unsynapsed chromatin. Together, these results on the developmental time course for nuclear localization of PRDM9 establish its direct window of function and demonstrate the independence of chromosome axial element formation from the concurrent PRDM9-mediated activation of recombination hotspots.

Mapping Water Vulnerability of the Yangtze River Basin: 1994-2013.

A holistic understanding of the magnitude and long-term trend of water vulnerability is essential for making management decisions in a given river basin. Existing procedures to assess the spatiotemporal dynamic of water vulnerability in complex mega-scale river basins are inadequate; a new method named ensemble hydrologic assessment was proposed in this study, which allows collection of data and knowledge about many aspects of water resources to be synthesized in a useful way for vulnerability assessment. The objective of this study is to illustrate the practical utility of such an integrated approach in examining water vulnerability in the Yangtze River Basin. Overall, the results demonstrated that the ensemble hydrologic assessment model could largely explain the spatiotemporal evolution of water vulnerability. This paper improves understanding of the status and trends of water resources in the Yangtze River Basin.

Meiosis arrest female 1 (MARF1) has nuage-like function in mammalian oocytes.

Orderly regulation of meiosis and protection of germline genomic integrity from transposable elements are essential for male and female gamete development. In the male germline, these processes are ensured by proteins associated with cytoplasmic nuage, but morphologically similar germ granules or nuage have not been identified in mammalian female germ cells. Indeed, many mutations affecting nuage-associated proteins such as PIWI and tudor domain containing proteins 5 and 7 (TDRD5/7) can result in failure of meiosis, up-regulation of retrotransposons, and infertility only in males and not in females. We recently identified MARF1 (meiosis arrest female 1) as a protein essential for controlling meiosis and retrotransposon surveillance in oocytes; and in contrast to PIWI-pathway mutations, Marf1 mutant females are infertile, whereas mutant males are fertile. Here we put forward the hypothesis that MARF1 in mouse oocytes is a functional counterpart of the nuage-associated components of spermatocytes. We describe the developmental pattern of Marf1 expression and its roles in retrotransposon silencing and protection from DNA double-strand breaks. Analysis of MARF1 protein domains compared with PIWI and TDRD5/7 revealed that these functional similarities are reflected in remarkable structural analogies. Thus, functions that in the male germline require protein interactions and cooperative scaffolding are combined in MARF1, allowing a single molecule to execute crucial activities of meiotic regulation and protection of germline genomic integrity.

Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells.

Basigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction since male knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and mature spermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulates formation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertoli cell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosome synapsis and progression through meiosis. However, only punctate expression of the round spermatid marker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating that spermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a large increase in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, we determined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans were significantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertoli cell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells. Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatly reduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) was compromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normal progression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to be necessary for integrity of the BTB and spermatocyte progression to mature spermatozoa.

Characterization and first flush analysis in road and roof runoff in Shenyang, China.

As urbanization increases, urban runoff is an increasingly important component of total urban non-point source pollution. In this study, the properties of urban runoff were examined in Shenyang, in northeastern China. Runoff samples from a tiled roof, a concrete roof and a main road were analyzed for key pollutants (total suspended solids (TSS), total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD), Pb, Cd, Cr, Cu, Ni, and Zn). The event mean concentration, site mean concentration, M(V) curves (dimensionless cumulative curve of pollutant load with runoff volume), and mass first flush ratio (MFF30) were used to analyze the characteristics of pollutant discharge and first flush (FF) effect. For all events, the pollutant concentration peaks occurred in the first half-hour after the runoff appeared and preceded the flow peaks. TN is the main pollutant in roof runoff. TSS, TN, TP, Pb, and Cr are the main pollutants in road runoff in Shenyang. There was a significant correlation between TSS and other pollutants except TN in runoff, which illustrated that TSS was an important carrier of organic matter and heavy metals. TN had strong positive correlations with total rainfall (Pearson's r = 0.927), average rainfall (Pearson's r = 0.995), and maximum rainfall intensity (Pearson's r = 0.991). TP had a strong correlation with rainfall intensity (Pearson's r = 0.940). A significant positive correlation between COD and rainfall duration (Pearson's r = 0.902, significance level = 0.05) was found. The order of FF intensity in different surfaces was concrete roof > tile roof > road. Rainfall duration and the length of the antecedent dry period were positively correlated with the FF. TN tended to exhibit strong flush for some events. Heavy metals showed a substantially stronger FF than other pollutant.

Gender disparities in summer outdoor heat risk across China: Findings from a national county-level assessment during 1991-2020.

Increasing anthropogenic global warming has emerged as a significant challenge to human health in China, as extreme heat hazards increasingly threaten outdoor-exposed populations. Differences in thermal comfort, outdoor activity duration, and social vulnerability between females and males may exacerbate gender inequalities in heat-related health risks, which have been overlooked by previous studies. Here, we combine three heat hazards and outdoor activity duration to identify the spatiotemporal variation in gender-specific heat risk in China during 1991-2020. We found that females' heat risk tends to be higher than that of males. Gender disparities in heat risk decrease in southern regions, while those in northern regions remain severe. Males are prone to overheating in highly urbanized areas, while females in low urbanized areas. Males' overheating risk is mainly attributed to population clustering associated with prolonged outdoor activity time and skewed social resource allocation. In contrast, females' overheating risk is primarily affected by social inequalities. Our findings suggest that China needs to further diminish gender disparities and accelerate climate adaptation planning.

A single cell atlas of the mouse seminal vesicle.

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest of mouse spermatocytes.

The ENU-induced repro8 mutation was identified in a screen to uncover genes that control mouse gametogenesis. repro8 causes male-limited infertility, with failure of spermatocytes to exit meiotic prophase via the G2/MI transition. The repro8 mutation is in the Eif4g3 gene, encoding eukaryotic translation initiation factor 4, gamma 3. Mutant germ cells appear to execute events of meiotic prophase normally, and many proteins characteristic of the prophase-to-metaphase transition are not obviously depleted. However, activity of CDC2A (CDK1) kinase is dramatically reduced in mutant spermatocytes. Strikingly, HSPA2, a chaperone protein for CDC2A kinase, is absent in mutant spermatocytes in spite of the presence of Hspa2 transcript, consistent with the observation that the repro8 phenotype is markedly similar to the phenotype of the Hspa2 knockout. Thus, EIF4G3 is required for HSPA2 translation in spermatocytes, a finding that provides the first genetic evidence for selective translational control of meiotic exit in mammalian spermatocytes.

Parameter calibration of the discrete element simulation model for soaking paddy loam soil based on the slump test.

The discrete element computer simulation method is an effective tool that enables the study of the interaction mechanism between the pulping components and the paddy soil during the paddy field pulping process. The findings are valuable in optimizing the parameters of the paddy beating device to improve its working quality and efficiency. However, the lack of accurate soil models for paddy soil has limited the application and development of the discrete element method in paddy pulping research. This study selected the Hertz-Mindlin with Johnson-Kendall-Roberts discrete element model for the pre-pulping paddy loam soil and used the slump error as the test index to select nine parameters, including soil Poisson's ratio and surface energy, as test factors to calibrate the model parameters. The Plackett-Burman test identified soil shear modulus, surface energy, and soil-iron plate static friction coefficient as significant factors affecting the test index. The steepest ascent test results determined the test range of the above parameters. The Box-Behnken test obtained the regression model between the significant factors and the test index, and the regression model was optimized using the slump error as the target. The optimal combination of parameters was surface energy of 3.257 J/m2, soil shear modulus of 0.709 MPa, and static friction coefficient between soil and iron plate of 0.701. The slump simulation test using this combination of parameters yielded an average slump error of 2.04%. The collective results indicate the accuracy of the calibrated discrete element simulation parameters for paddy loam soil. These parameters can be used for discrete element simulation analysis of the paddy pulping process after paddy field soaking.

Evidence for RNA or protein transport from somatic tissues to the male reproductive tract in mouse.

The development of tools to manipulate the mouse genome, including knockout and transgenic technology, has revolutionized our ability to explore gene function in mammals. Moreover, for genes that are expressed in multiple tissues or at multiple stages of development, the use of tissue-specific expression of the Cre recombinase allows gene function to be perturbed in specific cell types and/or at specific times. However, it is well known that putative tissue-specific promoters often drive unanticipated 'off-target' expression. In our efforts to explore the biology of the male reproductive tract, we unexpectedly found that expression of Cre in the central nervous system resulted in recombination in the epididymis, a tissue where sperm mature for ~1-2 weeks following the completion of testicular development. Remarkably, we not only observed reporter expression in the epididymis when Cre expression was driven from neuron-specific transgenes, but also when Cre expression in the brain was induced from an AAV vector carrying a Cre expression construct. A surprisingly wide range of Cre drivers - including six different neuronal promoters as well as the adipose-specific Adipoq Cre promoter - exhibited off-target recombination in the epididymis, with a subset of drivers also exhibiting unexpected activity in other tissues such as the reproductive accessory glands. Using a combination of parabiosis and serum transfer experiments, we find evidence supporting the hypothesis that Cre may be trafficked from its cell of origin to the epididymis through the circulatory system. Together, our findings should motivate caution when interpreting conditional alleles, and suggest the exciting possibility of inter-tissue RNA or protein trafficking in modulation of reproductive biology.

Vegetation coverage change of the demonstration area of ecologically friendly development in the Yangtze River Delta, China based on GEE and BRT during 1984-2019.

The demonstration area of ecologically friendly development in the Yangtze River Delta is a major national strategy area, and thus eco-environmental protection should be a priority for the sustainable development. Exploring the spatial-temporal variations of franctional vegetation coverage (FVC) is conducive to accurate assessing the ecological quality of environment, which is of great significance to regional sustainable development. In this study, the characteristics and trends of spatial-temporal variation of vegetation cover during 1984-2019 in the demonstration area were analyzed based on Google Earth Engine (GEE). The effects of different ecological factors on FVC were quantified by the boosted regression tree (BRT). Results showed that,the changing trend of FVC in the study area shifted from decreasing to increasing trend from 1984 to 2019. The spatial distribution of FVC in the study area varied with both stages and regions. FVC was mainly degraded. Compared with the year 1984, the area of vegetation degradation and improvement in 2019 accounted for 49.8% and 12.8%, respectively. The vegetation degradation mainly occurred in the north of Wujiang, south of Jiashan, and northeast of Qingpu. Human activities severely weakened the influence of natural factors on FVC. Our findings suggested that the GEE is an effective tool for monitoring the dynamics of vegetation coverage.

Mapping multiple water pollutants across China using the grey water footprint.

The primary pollutants and pollution levels of surface water present spatial and temporal changes. This study quantified the grey water footprint (GWF) and surface water pollution level (WPL) in China from 2003 to 2018 based on four pollutants: chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN) and total phosphorus (TP). Additionally, the spatiotemporal distribution of the primary water pollutant (PWP) and driving forces of the GWF were analyzed based on the WPLs and the logarithmic mean Divisia index (LMDI) decomposition method. The results showed that the GWF in China decreased by 13% from 2003 to 2018 and the WPL decreased from 1.11 in 2003 to 0.94 in 2018. An analysis of regional GWFs with multiple pollutants could prevent the underestimation of GWFs and WPLs caused by changes in the PWPs. The GWF spatial distribution was high in the southeast and low in the northwest, while the provinces with larger WPLs were mainly concentrated in northern China. The PWP changed from COD to TN in 2007 because of the increase in nitrogen application in China, the low TN reduction capacity of wastewater treatment plants and the improved comprehensive utilization rate of livestock and poultry manure. The driving force analysis results showed that water efficiency and technological and industrial structural effects promoted the reduced GWF. Our research conclusions and policy suggestions could provide references for reducing the GWF and improving the water quality in China.

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Vertical expansion makes the structure and pattern of the city more complicated. Traditional two-dimensional landscape pattern cannot completely reflect the ecological structure and functional characteristics of urban landscape. In this study, we used the three-dimensional landscape pattern metrics to quantify the regional three-dimensional landscape pattern, and used boosted regression tree (BRT) machine learning algorithms to comprehensively analyze the interaction between social-environmental factors and urban landscape patterns in the central part of Shanghai. Results showed that high building ratio, mean architecture height, and architecture height standard deviation had higher values in the surrounding area of the inner ring. The number of buildings and landscape shape index were higher in the outer ring than those in other area. Building coverage ratio, floor area ratio and Shannon's diversity index had higher values in the central part, with the metrics of Puxi being generally higher than those of Pudong. Population density and normalized vegetation index (NDVI) interacted most significantly with the three-dimensional landscape pattern, with GDP as the least influential factor. Within a certain range, the three-dimensional landscape pattern metrics increased with larger population density in the social factors, and decreased with lower rate of NDVI and water surface ratio in the environmental factors. Our results demonstrated that the BRT method was effective in quantifying the interaction between landscape pattern and social-environmental factors. Our results help improve the understanding of the relationship between ecological environment and human well-being in the central part of Shanghai and provide a scientific basis for the urban three-dimensional expansion planning.