Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian resto...Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.展开更多
Aim： To determine if Yq microdeletion frequency and loci of deletion are similar in two tissues （blood and sperm） of different embryological origin. Methods： The present study included 52 infertile oligozoospermic...Aim： To determine if Yq microdeletion frequency and loci of deletion are similar in two tissues （blood and sperm） of different embryological origin. Methods： The present study included 52 infertile oligozoospermic cases. In each case, DNA was isolated from blood and sperms and polymerase chain reaction （PCR） microdeletion analysis was done from genomic DNA isolated from both the tissues. The PCR products were analyzed on a 1.8% agarose gel. PCR amplifications found to be negative were repeated at least three times to confirm the deletion of a given marker. Results： Only 1 case harbored microdeletion in blood DNA, whereas 4 cases harbored microdeletion in sperm DNA. Conclusion： The frequency of Yq microdeletions is higher in germ cells as compared to blood. As the majority of infertile couples opt for assisted reproduction procreation techniques （ART）, Yq microdeletion screening from germ cells is important to understand the genetic basis of infertility, to provide comprehensive counseling and most adapted therapeutics to the infertile couple.展开更多
The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting(MACS)in sperm preparation for male subjects with a sperm DNA fragmentation index(DFI)≥30%.A total of 86 patients who had un...The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting(MACS)in sperm preparation for male subjects with a sperm DNA fragmentation index(DFI)≥30%.A total of 86 patients who had undergone their first long-term long protocol were selected.The protocol involved in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI)cycles,and the patients were divided into the MACS or control groups.The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation(DGC)and the swim-up(SU)technique(n=39),and the control group included sperm samples prepared using standard techniques(DGC and SU;n=41).No differences were noted with regard to basic clinical characteristics,number of oocytes retrieved,normal fertilization rate,cleavage rate,or transplantable embryo rate between the two groups in IVF/ICSI.In addition,the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups.However,there was a tendency to improve the live birth rate(LBR)of the first embryo transfer cycle(63.2%vs 53.9%)and the cumulative LBR(79.5%vs 70.7%)in the MACS group compared with the control group.Moreover,the number of transferred embryos(mean±standard deviation[s.d.]:1.7±0.7 vs 2.3±1.6)and the transfer number of each retrieved cycle(mean±s.d.:1.2±0.5 vs 1.6±0.8)were significantly lower in the MACS group than those in the control group.Thus,the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.展开更多
The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-...The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.展开更多
AIM:To evaluate telomere length in sperm DNA and its correlation with oxidative stress(normal,mild,severe).METHODS:The study included infertile men(n=112)and age matched fertile controls(n=102).The average telomere le...AIM:To evaluate telomere length in sperm DNA and its correlation with oxidative stress(normal,mild,severe).METHODS:The study included infertile men(n=112)and age matched fertile controls(n=102).The average telomere length from the sperm DNA was measured using a quantitative real time PCR based assay.Seminal reactive oxygen species(ROS)and 8-Isoprostane(8-IP)levels were measured by chemiluminescence assay and ELISA respectively.RESULTS:Average sperm telomere length in infertile men and controls was 0.609±0.15 and 0.789±0.060,respectively(P<0.0001).Seminal ROS levels in infertile was higher[66.61±28.32 relative light units(RLU)/s/million sperm]than in controls(14.04±10.67RLU/s/million sperm)(P<0.0001).The 8-IP level in infertile men was significantly higher(421.55±131.29pg/mL)than in controls(275.94±48.13 pg/mL)(P<0.001).When correlated to oxidative stress,in normal range of oxidative stress(ROS,0-21.3 RLU/s/million sperm)the average telomere length in cases was 0.663±0.14,in mild oxidative stress(ROS,21.3-35 RLU/s/million sperm)it was elevated(0.684±0.12)and in severe oxidative stress(ROS>35 RLU/s/million sperm)average telomere length was decreased to 0.595±0.15.CONCLUSION:Mild oxidative stress results in lengthening of telomere length,but severe oxidative stress results in shorter telomeres.Although telomere maintenance is a complex trait,the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological levels.Detailed molecular evaluation of telomere structure,its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition.展开更多
A high sperm DNA fragmentation index （DFI） is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant...A high sperm DNA fragmentation index （DFI） is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant and free radical scavenger, could thus impact semen quality and fertility. The association between the major melatonin metabolite, urine 6-sulfatoxymelatonin （aMT6s）, and DFI was analyzed in 110 Oslo men （south of the Arctic Circle） and 86 Tromsoe men （north of the Arctic Circle）. Two semen analyses, summer and winter, and four urine samples （early/late summer; early/late winter）, were analyzed. The associations between aMT6s in urine and DFI were characterized in a cross-sectional and longitudinal manner using correlation analysis and linear regression. Regardless of season and location, no significant correlations between aMT6s and DFI were observed. The correlation coefficients for associations between changes over time （early winter-early summer） in aMT6s and DFI were for the total cohort： rho = -0.08 （P = 0.322）, for the Oslo cohort： rho = -0.07 （P = 0.485）, and for the Tromsoe cohort： rho = -0.14 （P = 0.273）, respectively. Similar results were seen when comparing late winter and late summer. There was no any statistically significant correlation between changes over time in aMT6s and DFI for men with DFI below and above the median value （10%）, respectively. The seasonal variation in melatonin excretion seems not to have any impact on DFh展开更多
Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals （EDCs）. The increasin...Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals （EDCs）. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.展开更多
Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how centra...Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.展开更多
Aim： To identify flutamide regulated genes in the rat ventral prostate. Methods： Total RNA from ventral prostates of control and flutamide treated rats were isolated. Differentially expressed transcripts were identi...Aim： To identify flutamide regulated genes in the rat ventral prostate. Methods： Total RNA from ventral prostates of control and flutamide treated rats were isolated. Differentially expressed transcripts were identified using differential display reverse transcriptase polymerase chain reaction. The effect of castration on the expression of flutamideregulated transcripts was studied. Results： We have identified β2-microglobulin, cytoplasmic FMR1 interacting protein 2 and pumilio 1 as flutamide induced and spermine binding protein and ribophorin Ⅱ as flutamide repressed targets in the rat ventral prostate. Although flutamide treatment caused an induction of pumilio 1 rnRNA, castration had no effect. Conclusion： Castration and flutamide treatments exert differential effects on gene expression. Flutamide might also have direct AR independent effects, which might have implications in the emergence of androgen independent prostate cancer and the failure of flutamide therapy.展开更多
Aim: To demonstrate the role of the 8 kDa peptide in regulation of testosterone production by mt Leydig cells. Meth-ods: A peptide similar to 8 kDa peptide purified from immature rat Leydig cells was isolated and puri...Aim: To demonstrate the role of the 8 kDa peptide in regulation of testosterone production by mt Leydig cells. Meth-ods: A peptide similar to 8 kDa peptide purified from immature rat Leydig cells was isolated and purified from rat lungcytosol. Immunological and structural similarity between the peptides purified from lung and Leydig cells was estab-lished by Western blot and tryptic map comparison respectively. Results: Addition of the 8 kDa peptide 10, 50, 100;and 150 ug decreased the production of testosterone in Leydig cells dose-dependently. But the addition of the peptide150 ug along with hCG had no effect on hCG-stimulated increase in testosterone production. Conclusion: In vitro ad-dition of the peptide purified from lung cytosol to adult rat Leydig cells resulted in a concentration-dependent decrease inbasal testosterone production although it had no effect on hCG-stimulated testosterone production. (Asian J Androl1999 Dec; 1: 191-194)展开更多
Ageing is associated with declined activity of behaviors, physiology and metabolic processes （Arking, 2006）. In- vestigations in model organisms have indicated the exis- tence of ＂functional senescence＂, the progr...Ageing is associated with declined activity of behaviors, physiology and metabolic processes （Arking, 2006）. In- vestigations in model organisms have indicated the exis- tence of ＂functional senescence＂, the progressive decline of biological functions with age and the decline in the activity may vary from tissue to tissue. Consequently, studies per- taining to the key organs/tissues whose functions deterio- rate/fail with age have led to the development of tissue specific ageing biomarkers （Grotewiel et al., 2005; Demontis et al., 2013）.展开更多
Assisted procreation techniques have revolutionized the management of infertility and have offered hope to millions of infertile couples. The main aim of these procedures is to produce healthy offspring. However recen...Assisted procreation techniques have revolutionized the management of infertility and have offered hope to millions of infertile couples. The main aim of these procedures is to produce healthy offspring. However recent studies on short term outcome of ART have reported a higher incidence of low birth weight, development delay, imprinting defects, sex and autosomal structural abnormalities, major and minor congenital malformation and certain cancers in babies conceived via ART. Further the health of ART conceived children beyond the neonatal period have been less well evaluated. A large number of infertile couples opting for ART have an underlying genetic aetiology. These genetic aberrations are iatrogenitically transmitted via ART. Thus it is important that all couples undergo a detailed and comprehensive genetic evaluation prior to ART.展开更多
Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal ab...Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal abnormalities ranging from 2.2% to 15.7% in infertile men. The present study has been carried out to document and find out the genetic cause of male infertility in the Southern region of India. The cytogenetic analysis of 200 male infertile cases, referred due to primary infertility from 2009 to 2012, were analyzed by GTG banding and evaluated retrospectively. The semen analysis was also performed. A total of 15 cases (7.5%) showed chromosomal aberrations. Four (2%) were 47, XXY and mosaic 47,XXY;Two (1%) were structural autosomal abnormalities;Two (1%) were inversion Y;Seven (3.5%) cases were Y heterochromatin variants and 185 cases (92.5%) showed normal 46,XY karyotype. The chromosomal abnormalities in our study is also in agreement with the data from the literature. Also abnormal spermatogenesis is observed in these cases. Apart from chromosomal analysis further in depth molecular analysis and genetic counseling is suggestive in such cases, especially those interested in IVF technologies.展开更多
We show that the cytotoxic effect of carbon nanotubes (CNTs) on bacteria is mediated by mechanical damage to the cell wall and membrane. Two β-galactosidase-producing strains of Escherichia coli harboringgenomically ...We show that the cytotoxic effect of carbon nanotubes (CNTs) on bacteria is mediated by mechanical damage to the cell wall and membrane. Two β-galactosidase-producing strains of Escherichia coli harboringgenomically integrated reporter gene constructs, namely pchbB:lacZand prpoS:lacZ, were used for the purpose. We first verified that CNTs result in an inhibition of cell growth. Enzyme activity was determined using a reporter gene assay in which CNTs were used without the lysis buffer (containing detergent). β-galactosidase activity in the presence of CNTs alone measured several fold more than the controls used (without nanotubes). This suggests that CNTs damage the cell membrane in a manner similar to the detergent in the lysis buffer and render E. coli cell walls porous, causing cell contents including enzymes to leak out into the medium. Our results support the hypothesis that mechanical damage to bacterial cell membranes is the prevailing cause of CNT-cytotoxicity.展开更多
Both fatty acids (FAs) and calcium ions play important roles in contraceptive cyclesvia several systems. Polyunsaturated FAs (PUFAs) act as precursors for prostaglandin production and can alter the expression of numer...Both fatty acids (FAs) and calcium ions play important roles in contraceptive cyclesvia several systems. Polyunsaturated FAs (PUFAs) act as precursors for prostaglandin production and can alter the expression of numerous crucial catalysts that are involved in prostaglandin and steroid digestion. Lipids are essential components of cell membranes. A diet rich in PUFAs enhances sperm motility and viability. It also improves testis development and spermatogenesis in several domesticated animal species. Increased PUFA content in spermatozoa increases plasma membrane fluidity, which is important for fertilization. However, the major drawback of high dietary PUFA intake is that it increases the levels of reactive oxygen species in the body. An increase in reactive oxygen species levels markedly affects fertility. Calcium is an important component that acts as an intra-cellular secondary messenger and plays an important role in some of the physiological processes that occur in male gametes. Some of these processes include spermatogenesis, sperm motility, capacitation, acrosome response, and fusion of gametes. These processes are associated with calcium influx through ion protein channels. Dietary fat intake is associated with increased intestinal calcium absorption. In this review, we discuss the impact of lipids, particularly PUFAs and monounsaturated FAs, and calcium ions on male reproduction, along with their effects on each other.展开更多
Gonadal soma-derived factor(Gsdf)is a member of the transforming growth factor beta(TGF-β)superfamily and a teleost-specific gene.Early studies suggested that Gsdf promotes spermatogonial proliferation;however recent...Gonadal soma-derived factor(Gsdf)is a member of the transforming growth factor beta(TGF-β)superfamily and a teleost-specific gene.Early studies suggested that Gsdf promotes spermatogonial proliferation;however recent reports have shed light on its role in sex differentiation based on expression profiles and gain-and loss-of-function studies.This paper discusses the involvement of Gsdf in gonadal sex differentiation and sex changes in teleosts.展开更多
Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cell...Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.展开更多
The impact of coronavirus disease 2019(COVID-19)on endometriosis(EM)is currently unclear.Here,we aimed to describe the potential influence of COVID-19 on the pathogenesis,clinical symptoms,and treatment of EM.The cyto...The impact of coronavirus disease 2019(COVID-19)on endometriosis(EM)is currently unclear.Here,we aimed to describe the potential influence of COVID-19 on the pathogenesis,clinical symptoms,and treatment of EM.The cytokine storm caused by COVID-19 may induce the occurrence and progression of EM,and immunosuppression of COVID-19 may help the ectopic endometrium escape from immune clearance.Consequently,the forced social isolation and the cancelation of non-emergency medical treatment during the COVID-19 pandemic aggravate anxiety and psychological pressure,which can aggravate the symptoms related to EM and delay routine medical services.展开更多
The rapid and label-free diagnosis of malignancies in ex vivo breast biopsy tissues has significant utility in pathology laboratories and operating rooms.We report a MEMS-based platform integrated with microchips that...The rapid and label-free diagnosis of malignancies in ex vivo breast biopsy tissues has significant utility in pathology laboratories and operating rooms.We report a MEMS-based platform integrated with microchips that performs phenotyping of breast biopsy tissues using electrothermal sensing.The microchip,fabricated on a silicon substrate,incorporates a platinum microheater,interdigitated electrodes(IDEs),and resistance temperature detectors(RTDs)as on-chip sensing elements.The microchips are integrated onto the platform using a slide-fit contact enabling quick replacement for biological measurements.The bulk resistivity(ρB),surface resistivity(ρS),and thermal conductivity(k)of deparaffinized and formalin-fixed paired tumor and adjacent normal breast biopsy samples from N=8 patients were measured.For formalin-fixed samples,the meanρB for tumors showed a statistically significant fold change of 4.42(P=0.014)when the tissue was heated from 25°C to 37°C compared to the adjacent normal tissue,which showed a fold change of 3.47.The meanρS measurements also showed a similar trend.The mean k of the formalinfixed tumor tissues was 0.309±0.02Wm^(-1)K^(-1)compared to a significantly higher k of 0.563±0.028 Wm^(-1)K^(-1)for the adjacent normal tissues.A similar trend was observed inρB,ρS,and k for the deparaffinized tissue samples.An analysis of a combination ofρ_(B,)ρ_(S,)and k using Fisher’s combined probability test and linear regression suggests the advantage of using all three parameters simultaneously for distinguishing tumors from adjacent normal tissues with higher statistical significance.展开更多
Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that...Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies.This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods:To investigate the role of KLF12 in placentation,we employed a model of forskolin-induced syncytialization in BeWo cells.Results:Our findings revealed that KLF12 expression is downregulated during normal syncytialization.Conversely,we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1(GCM1)expression.This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization.Furthermore,we observed placental deformities in KLF12-overexpressing mouse fetuses.Conclusion(s):This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression.These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.展开更多
基金supported by the National Natural Science Foundation of China(82271671)Nanjing Drum Tower Hospital Academic Innovation Peak Fund(2024-DF-02)+4 种基金Clinical Trials from Nanjing Drum Tower Hospital(2023-LCYJ-MS-05)Nanjing International Science and Technology Cooperation Program(202201027)to L.D.Research Project of State Key Laboratory of Reproductive Medicine and Offspring Health(SKLRM-2022D2)Changzhou Medical Center of Nanjing Medical University(CMCM202203)Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-02)to H.S.
文摘Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.
文摘Aim： To determine if Yq microdeletion frequency and loci of deletion are similar in two tissues （blood and sperm） of different embryological origin. Methods： The present study included 52 infertile oligozoospermic cases. In each case, DNA was isolated from blood and sperms and polymerase chain reaction （PCR） microdeletion analysis was done from genomic DNA isolated from both the tissues. The PCR products were analyzed on a 1.8% agarose gel. PCR amplifications found to be negative were repeated at least three times to confirm the deletion of a given marker. Results： Only 1 case harbored microdeletion in blood DNA, whereas 4 cases harbored microdeletion in sperm DNA. Conclusion： The frequency of Yq microdeletions is higher in germ cells as compared to blood. As the majority of infertile couples opt for assisted reproduction procreation techniques （ART）, Yq microdeletion screening from germ cells is important to understand the genetic basis of infertility, to provide comprehensive counseling and most adapted therapeutics to the infertile couple.
基金supported by the National Natural Science Foundation of China(No.81801518 and No.82071646).
文摘The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting(MACS)in sperm preparation for male subjects with a sperm DNA fragmentation index(DFI)≥30%.A total of 86 patients who had undergone their first long-term long protocol were selected.The protocol involved in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI)cycles,and the patients were divided into the MACS or control groups.The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation(DGC)and the swim-up(SU)technique(n=39),and the control group included sperm samples prepared using standard techniques(DGC and SU;n=41).No differences were noted with regard to basic clinical characteristics,number of oocytes retrieved,normal fertilization rate,cleavage rate,or transplantable embryo rate between the two groups in IVF/ICSI.In addition,the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups.However,there was a tendency to improve the live birth rate(LBR)of the first embryo transfer cycle(63.2%vs 53.9%)and the cumulative LBR(79.5%vs 70.7%)in the MACS group compared with the control group.Moreover,the number of transferred embryos(mean±standard deviation[s.d.]:1.7±0.7 vs 2.3±1.6)and the transfer number of each retrieved cycle(mean±s.d.:1.2±0.5 vs 1.6±0.8)were significantly lower in the MACS group than those in the control group.Thus,the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.
基金the Swedish Research Council(Grant Nos.521-2004-6072 and K2005-72X-14545-03A)the Swedish Cancer Society(Grant Nos.4857-B05-03XCC,070482 and 070139)the Gunnar Nilsson Cancer Fund and the Center for Research in the Elderly in Tromsø,Norway.
文摘The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.
基金Supported by Department of Biotechnology(DBT),Government of India,No.1369
文摘AIM:To evaluate telomere length in sperm DNA and its correlation with oxidative stress(normal,mild,severe).METHODS:The study included infertile men(n=112)and age matched fertile controls(n=102).The average telomere length from the sperm DNA was measured using a quantitative real time PCR based assay.Seminal reactive oxygen species(ROS)and 8-Isoprostane(8-IP)levels were measured by chemiluminescence assay and ELISA respectively.RESULTS:Average sperm telomere length in infertile men and controls was 0.609±0.15 and 0.789±0.060,respectively(P<0.0001).Seminal ROS levels in infertile was higher[66.61±28.32 relative light units(RLU)/s/million sperm]than in controls(14.04±10.67RLU/s/million sperm)(P<0.0001).The 8-IP level in infertile men was significantly higher(421.55±131.29pg/mL)than in controls(275.94±48.13 pg/mL)(P<0.001).When correlated to oxidative stress,in normal range of oxidative stress(ROS,0-21.3 RLU/s/million sperm)the average telomere length in cases was 0.663±0.14,in mild oxidative stress(ROS,21.3-35 RLU/s/million sperm)it was elevated(0.684±0.12)and in severe oxidative stress(ROS>35 RLU/s/million sperm)average telomere length was decreased to 0.595±0.15.CONCLUSION:Mild oxidative stress results in lengthening of telomere length,but severe oxidative stress results in shorter telomeres.Although telomere maintenance is a complex trait,the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological levels.Detailed molecular evaluation of telomere structure,its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition.
文摘A high sperm DNA fragmentation index （DFI） is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant and free radical scavenger, could thus impact semen quality and fertility. The association between the major melatonin metabolite, urine 6-sulfatoxymelatonin （aMT6s）, and DFI was analyzed in 110 Oslo men （south of the Arctic Circle） and 86 Tromsoe men （north of the Arctic Circle）. Two semen analyses, summer and winter, and four urine samples （early/late summer; early/late winter）, were analyzed. The associations between aMT6s in urine and DFI were characterized in a cross-sectional and longitudinal manner using correlation analysis and linear regression. Regardless of season and location, no significant correlations between aMT6s and DFI were observed. The correlation coefficients for associations between changes over time （early winter-early summer） in aMT6s and DFI were for the total cohort： rho = -0.08 （P = 0.322）, for the Oslo cohort： rho = -0.07 （P = 0.485）, and for the Tromsoe cohort： rho = -0.14 （P = 0.273）, respectively. Similar results were seen when comparing late winter and late summer. There was no any statistically significant correlation between changes over time in aMT6s and DFI for men with DFI below and above the median value （10%）, respectively. The seasonal variation in melatonin excretion seems not to have any impact on DFh
文摘Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals （EDCs）. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.
基金supported by a grant from All India Institute of Medical Sciences,New Delhi (to RD and TD)Indian Council of Medical Research,Senior Research Fellowship Grant (3/1/2(24)/oph-2009-NCD-II,to MAF)+1 种基金Feldstein Medical Foundation Research Grant (to KCC)unrestricted fund from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology (to KCC)。
文摘Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance my lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.
文摘Aim： To identify flutamide regulated genes in the rat ventral prostate. Methods： Total RNA from ventral prostates of control and flutamide treated rats were isolated. Differentially expressed transcripts were identified using differential display reverse transcriptase polymerase chain reaction. The effect of castration on the expression of flutamideregulated transcripts was studied. Results： We have identified β2-microglobulin, cytoplasmic FMR1 interacting protein 2 and pumilio 1 as flutamide induced and spermine binding protein and ribophorin Ⅱ as flutamide repressed targets in the rat ventral prostate. Although flutamide treatment caused an induction of pumilio 1 rnRNA, castration had no effect. Conclusion： Castration and flutamide treatments exert differential effects on gene expression. Flutamide might also have direct AR independent effects, which might have implications in the emergence of androgen independent prostate cancer and the failure of flutamide therapy.
文摘Aim: To demonstrate the role of the 8 kDa peptide in regulation of testosterone production by mt Leydig cells. Meth-ods: A peptide similar to 8 kDa peptide purified from immature rat Leydig cells was isolated and purified from rat lungcytosol. Immunological and structural similarity between the peptides purified from lung and Leydig cells was estab-lished by Western blot and tryptic map comparison respectively. Results: Addition of the 8 kDa peptide 10, 50, 100;and 150 ug decreased the production of testosterone in Leydig cells dose-dependently. But the addition of the peptide150 ug along with hCG had no effect on hCG-stimulated increase in testosterone production. Conclusion: In vitro ad-dition of the peptide purified from lung cytosol to adult rat Leydig cells resulted in a concentration-dependent decrease inbasal testosterone production although it had no effect on hCG-stimulated testosterone production. (Asian J Androl1999 Dec; 1: 191-194)
基金supported by financial assistance from Department of Science and Technology and Department of Biotechnology,Government of India and Indian Institute of Science to Upendra Nongthomba
文摘Ageing is associated with declined activity of behaviors, physiology and metabolic processes （Arking, 2006）. In- vestigations in model organisms have indicated the exis- tence of ＂functional senescence＂, the progressive decline of biological functions with age and the decline in the activity may vary from tissue to tissue. Consequently, studies per- taining to the key organs/tissues whose functions deterio- rate/fail with age have led to the development of tissue specific ageing biomarkers （Grotewiel et al., 2005; Demontis et al., 2013）.
文摘Assisted procreation techniques have revolutionized the management of infertility and have offered hope to millions of infertile couples. The main aim of these procedures is to produce healthy offspring. However recent studies on short term outcome of ART have reported a higher incidence of low birth weight, development delay, imprinting defects, sex and autosomal structural abnormalities, major and minor congenital malformation and certain cancers in babies conceived via ART. Further the health of ART conceived children beyond the neonatal period have been less well evaluated. A large number of infertile couples opting for ART have an underlying genetic aetiology. These genetic aberrations are iatrogenitically transmitted via ART. Thus it is important that all couples undergo a detailed and comprehensive genetic evaluation prior to ART.
文摘Chromosomal abnormalities are one of the major causes of male infertility. But the exact mechanism by which chromosomal anomalies induces infertility is still not clear. Many studies have documented the chromosomal abnormalities ranging from 2.2% to 15.7% in infertile men. The present study has been carried out to document and find out the genetic cause of male infertility in the Southern region of India. The cytogenetic analysis of 200 male infertile cases, referred due to primary infertility from 2009 to 2012, were analyzed by GTG banding and evaluated retrospectively. The semen analysis was also performed. A total of 15 cases (7.5%) showed chromosomal aberrations. Four (2%) were 47, XXY and mosaic 47,XXY;Two (1%) were structural autosomal abnormalities;Two (1%) were inversion Y;Seven (3.5%) cases were Y heterochromatin variants and 185 cases (92.5%) showed normal 46,XY karyotype. The chromosomal abnormalities in our study is also in agreement with the data from the literature. Also abnormal spermatogenesis is observed in these cases. Apart from chromosomal analysis further in depth molecular analysis and genetic counseling is suggestive in such cases, especially those interested in IVF technologies.
文摘We show that the cytotoxic effect of carbon nanotubes (CNTs) on bacteria is mediated by mechanical damage to the cell wall and membrane. Two β-galactosidase-producing strains of Escherichia coli harboringgenomically integrated reporter gene constructs, namely pchbB:lacZand prpoS:lacZ, were used for the purpose. We first verified that CNTs result in an inhibition of cell growth. Enzyme activity was determined using a reporter gene assay in which CNTs were used without the lysis buffer (containing detergent). β-galactosidase activity in the presence of CNTs alone measured several fold more than the controls used (without nanotubes). This suggests that CNTs damage the cell membrane in a manner similar to the detergent in the lysis buffer and render E. coli cell walls porous, causing cell contents including enzymes to leak out into the medium. Our results support the hypothesis that mechanical damage to bacterial cell membranes is the prevailing cause of CNT-cytotoxicity.
基金The first author Taniya Naz is funded by University Grants Commission Junior Research Fellowship(UGC-RF)and the lab expenses including second author's fellowship(JRF)is funded by the Science and Engineering Research Board-Start up Research Grant(SERB-SRG)(Grant No.:SRG/2019/000501)of Department of Science and Technology,New Delhi,India.
文摘Both fatty acids (FAs) and calcium ions play important roles in contraceptive cyclesvia several systems. Polyunsaturated FAs (PUFAs) act as precursors for prostaglandin production and can alter the expression of numerous crucial catalysts that are involved in prostaglandin and steroid digestion. Lipids are essential components of cell membranes. A diet rich in PUFAs enhances sperm motility and viability. It also improves testis development and spermatogenesis in several domesticated animal species. Increased PUFA content in spermatozoa increases plasma membrane fluidity, which is important for fertilization. However, the major drawback of high dietary PUFA intake is that it increases the levels of reactive oxygen species in the body. An increase in reactive oxygen species levels markedly affects fertility. Calcium is an important component that acts as an intra-cellular secondary messenger and plays an important role in some of the physiological processes that occur in male gametes. Some of these processes include spermatogenesis, sperm motility, capacitation, acrosome response, and fusion of gametes. These processes are associated with calcium influx through ion protein channels. Dietary fat intake is associated with increased intestinal calcium absorption. In this review, we discuss the impact of lipids, particularly PUFAs and monounsaturated FAs, and calcium ions on male reproduction, along with their effects on each other.
基金supported by UK-Japan Research Collaboration Grants from the Ministry of the Environment,Japan,and JSPS KAKENHI grant No.18H02281 awarded to T.K.
文摘Gonadal soma-derived factor(Gsdf)is a member of the transforming growth factor beta(TGF-β)superfamily and a teleost-specific gene.Early studies suggested that Gsdf promotes spermatogonial proliferation;however recent reports have shed light on its role in sex differentiation based on expression profiles and gain-and loss-of-function studies.This paper discusses the involvement of Gsdf in gonadal sex differentiation and sex changes in teleosts.
基金supported by grants from the National Key Research and Development Program of China(2018YFC1004701)Nature Science Foundation of China(81871128 and 81571391)+4 种基金Nanjing Medical Science Development Project(ZKX16042)L.D.grants from Nature Science Foundation of China(82030040)Jiangsu Province Social Development Project(BE2018602)H.S.For this work,Bruno Péault has been supported by grants from the British Heart Foundation and BIRAX Regenerative Medicine Initiative.
文摘Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.
基金National Natural Science Foundation of China(82071646,81801530)
文摘The impact of coronavirus disease 2019(COVID-19)on endometriosis(EM)is currently unclear.Here,we aimed to describe the potential influence of COVID-19 on the pathogenesis,clinical symptoms,and treatment of EM.The cytokine storm caused by COVID-19 may induce the occurrence and progression of EM,and immunosuppression of COVID-19 may help the ectopic endometrium escape from immune clearance.Consequently,the forced social isolation and the cancelation of non-emergency medical treatment during the COVID-19 pandemic aggravate anxiety and psychological pressure,which can aggravate the symptoms related to EM and delay routine medical services.
基金Anil Vishnu G.K.acknowledges award funding from BIRAC under the SITAREGYTI scheme(BIRAC SRISTI PMU-2020/001)Anil Vishnu G.K.also acknowledges Midhun C.Kachappilly for helping with the experiments.Annapoorni Rangarajan acknowledges DBT-IISc partnership program.Hardik J.Pandya acknowledges the Core Research Grant support(CRG/2019/004963)from the Science and Engineering Research Board(SERB).
文摘The rapid and label-free diagnosis of malignancies in ex vivo breast biopsy tissues has significant utility in pathology laboratories and operating rooms.We report a MEMS-based platform integrated with microchips that performs phenotyping of breast biopsy tissues using electrothermal sensing.The microchip,fabricated on a silicon substrate,incorporates a platinum microheater,interdigitated electrodes(IDEs),and resistance temperature detectors(RTDs)as on-chip sensing elements.The microchips are integrated onto the platform using a slide-fit contact enabling quick replacement for biological measurements.The bulk resistivity(ρB),surface resistivity(ρS),and thermal conductivity(k)of deparaffinized and formalin-fixed paired tumor and adjacent normal breast biopsy samples from N=8 patients were measured.For formalin-fixed samples,the meanρB for tumors showed a statistically significant fold change of 4.42(P=0.014)when the tissue was heated from 25°C to 37°C compared to the adjacent normal tissue,which showed a fold change of 3.47.The meanρS measurements also showed a similar trend.The mean k of the formalinfixed tumor tissues was 0.309±0.02Wm^(-1)K^(-1)compared to a significantly higher k of 0.563±0.028 Wm^(-1)K^(-1)for the adjacent normal tissues.A similar trend was observed inρB,ρS,and k for the deparaffinized tissue samples.An analysis of a combination ofρ_(B,)ρ_(S,)and k using Fisher’s combined probability test and linear regression suggests the advantage of using all three parameters simultaneously for distinguishing tumors from adjacent normal tissues with higher statistical significance.
基金supported by the National Natural Science Foundation of China(82030040,82301897,and 82171653)the Natural Science Foundation of Nanjing Drum Tower Hospital,Nanjing University Medical School(2022-JCYJ-QP-54)the Natural Science Foundation of Shandong(ZR202111300553 and ZR2022MH094).
文摘Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies.This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods:To investigate the role of KLF12 in placentation,we employed a model of forskolin-induced syncytialization in BeWo cells.Results:Our findings revealed that KLF12 expression is downregulated during normal syncytialization.Conversely,we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1(GCM1)expression.This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization.Furthermore,we observed placental deformities in KLF12-overexpressing mouse fetuses.Conclusion(s):This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression.These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.
