BACKGROUND:At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT. METHODS:In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations. RESULTS:With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin. CONCLUSIONS:In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

Background Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin-angiotensin system (RAS) in human ovary and it plays a key role. Methods After collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells. Results First, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of functional follicles decreased, while the atresia follicles increased (P < 0.05). After MSCs transplantation, all the above measures have been partially recovered (P < 0.05). Although several RAS components in aging ovary changed, MSCs only improved the expression level of AT1R (P < 0.05). Furthermore, the secretion ability and mitochondrial membrane potential of aging KGN cells decreased, while the intracellular ROS level and the aging cells ratio increased (P < 0.01). All the above measures have been partially recovered when co-cultured with MSCs (P < 0.05). After Ang(1-7) were added into the co-culture system, the above have been more significantly restored compared with Ang II (P < 0.05). Nevertheless, there was no statistical difference in estradiol level no matter which one was added (P > 0.05). Conclusions Together, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.

Background: the context and purpose of the study Methods: how the study was performed and statistical tests used Results: the main findings Conclusions: Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of umbilical cord-derived mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. In recent years, it has been found that there is a local renin-angiotensin system (RAS) in human ovary and it plays a key role.In our research, local RAS of ovary, which is independent of circulating RAS, is affected by age and related to ovarian function. Furthermore, the in vivo(mice) and in vitro (KGN cells) experiments were designed to confirm that transplantation of MSCs improves age-related ovarian dysfunction by the local RAS. Together, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian dysfunction.

Objective: To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) outcome. Design: Study on the correlation of non-intervention. Setting: Reproductive Medicine Center, First Affiliated Hospital of Soochow University. Sample: hFF of 139 women who received IVF simply because of their husband’s factors from January 2021 to February 2022. Methods: The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF outcome. Main Outcome Measures: The levels of RAS components in hFF were measured, including Renin, ACE, ACE2, AngⅡ and Ang(1-7). Results: ①The influence of age on ACE-AngⅡ-AT1/2R axis was more significant than that on ACE2-Ang(1-7)-MAS axis in hFF; ②Provides evidence that gonadotropins mediate RAS activation of local ovarian follicles; ③It is still impossible to prove the effect of RAS on steroid hormone production, at least in ovarian follicles RAS cannot affect steroid hormones in the systemic circulation; ④Age and the level of RAS components in hFF have certain clinical value in predicting the number of oocyte retrieval and the rate of MⅡ maturation. Conclusions: The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF outcome.

BACKGROUND:Assisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases.METHODS:Male C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver.RESULTS:The growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption.CONCLUSIONS:The upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

Abstract Background Previous studies have found that there is the local renin-angiotensin system (RAS) in human ovary, and it independently plays a regulatory role in ovarian function. Age-related reproductive aging is an inevitable process. To explore the relationship between RAS components in human follicular fluid (hFF) and age, ovarian function, so as to help clinical evaluation of oocyte quality and prediction of in vitro fertilization (IVF) outcome. Methods hFF of 139 women who received IVF simply because of their husband's factors from January 2021 to February 2022. The levels of RAS components in hFF were measured, including Renin, ACE, ACE2, AngⅡ and Ang(1–7). The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF outcome. Results A total of 139 samples of analysable hFF were obtained in this study. It was found that there was a linear negative correlation between age and renin, ACE, AngⅡ, ACE/ACE2, AngⅡ/Ang(1–7) (Pearson's r < 0, P < 0.05), while the linear relationship with ACE2 and Ang (1–7) was not significant (P > 0.05). It was found that bFSH and bLH were correlated with age, ACE-AngⅡ-AT1/2R axis, ACE2-Ang(1–7)-MAS axis (P < 0.05), AFC was correlated with age, ACE2-Ang(1–7)-MAS axis (P < 0.05), and bAMH was only correlated with age (P < 0.01). There was no correlation between RAS and bE2, bP, bPRL, bT (P > 0.05). It was found that the number of oocyte retrieval and MⅡ maturation rate were correlated with age, renin, ACE-AngⅡ-AT1/2R axis and ACE2-Ang(1–7)-MAS axis (P < 0.05), and the rate of 2PN embryos, transplantable embryos, high-quality embryos were only correlated with age (P < 0.01). Conclusions ①The influence of age on ACE-AngⅡ-AT1/2R axis was more significant than that on ACE2-Ang(1–7)-MAS axis in hFF; ②Provides evidence that gonadotropins mediate RAS activation of local ovarian follicles; ③It is still impossible to prove the effect of RAS on steroid hormone production, at least in ovarian follicles RAS cannot affect steroid hormones in the systemic circulation; ④Age and the level of RAS components in hFF have certain clinical value in predicting the number of oocyte retrieval and the rate of MⅡ maturation.

Adverse environmental factors or prenatal insults may cause developmental and pathological changes in the brain [1] . Previous studies showed that a number of unfavorable prenatal factors might trigger the pathological changes of adult diseases such as hypertension and diabetes mellitus [2] . It is rational that inner-utero hypoxia could be a common problem of prenatal insults-induced development.

Objective:To study the biological processes associated with the premature ovarian failure (POF)-specific variants from the genome level.Methods:Bioinformatics analysis was performed by whole exome sequencing data from 3 POF patients and 7 healthy controls from 2 families. POF-specific single nucleotide variants (SNVs) and corresponding genes were used to execute biological function enrichment and protein interaction analysis.Results:Totally 262 disease-specific mutations were significantly enriched in multiple GO functional items, such as homophilic cell adhesion ( P=1.28E-3), cell adhesion ( P=3.56E-3), positive regulation of transcription ( P=9.41E-3), digestive tract development ( P=0.011), Notch signaling pathway ( P=0.018), calcium ion transmembrane transport ( P=0.021) and cellular response to decreased oxygen levels ( P=0.026) in the set of biological processes; plasma membrane ( P=2.58E-4), cell leading edge ( P=0.014), centriole ( P=0.016), dynein complex ( P=0.033), postsynaptic density ( P=0.035) in the set of cell component； transcription factor activity ( P=5.04E-3), profilin binding ( P=6.03E-3), calcium ion binding ( P=0.008), nucleosomal histone binding ( P=0.039), carbohydrate binding ( P=0.048) in the set of molecular function. A total of 262 genes were significantly enriched in multiple KEGG biological signaling pathways, such as dorso-ventral axis formation ( P=4.09E-4), thyroid hormone signaling pathway ( P=0.017), vasopressin-regulated water reabsorption ( P=0.020), Notch signaling pathway ( P=0.025) and Huntington's disease ( P=0.042). In addition, 262 genes encode proteins sets were performed to protein interaction network analysis, the result showed that MYC, FOXO1, CREBBP, NOTCH2, and HES1 were involved in the strong network clusters composed of core genes in the interaction network. Conclusion:POF-specific genetic changes may contribute to the development of POF by causing changes in the biological processes and activity of the signaling pathway of ovarian development. These evidence can provide a solid theoretical basis for further research on the heredity pathogenesis of premature ovarian failure.

目的 分析多囊卵巢综合征(PCOS)基因转录调控关联的生物信息.方法 从整合基因表达汇编平台中共下载PCOS患者33例及健康对照30例的皮下脂肪组织样本转录组测序数据,比较两组基因表达数据,保留P＜0.0005的1636个显著差异基因,进行GO数据库的功能富集分析和KEGG数据库的生物信号通路富集分析.结果 1636个显著差异基因富集在GO功能条目下,如在生物学过程集合中的嗜同性细胞黏附、肌丝滑动、肌肉收缩等,在细胞组分集合中的细胞质、肌原纤维节、核质等,在分子功能集合中的蛋白质结合、多聚腺嘌呤RNA结合及钙离子结合等(P＜0.001).1636个显著差异基因富集KEGG生物信号通路,如TNF信号通路、催产素信号通路、Ras信号通路、环磷酸腺苷信号通路、胰岛素信号通路及雌激素信号通路等(P＜0.05).结论 PCOS表达基因的遗传学变化可能通过影响卵巢发育生物学过程及卵巢发育相关的信号通路的活性,从而促进PCOS的发生.

目的 分析影响供精人工授精(AID)妊娠结局的相关因素.方法 回顾性分析苏州大学附属第一医院生殖医学中心2015年7月—2018年7月行AID助孕的213例患者,共计452周期的妊娠结局.结果 AID临床妊娠134例,周期妊娠率29.65％,累积妊娠率62.91％.女方年龄≤35岁组临床妊娠率明显高于>35岁组(30.94％vs 14.29％,P=0.038),不孕年限≤10年组临床妊娠率明显高于不孕年限>10年组(30.63％vs 9.52％,P=0.040),微刺激促排卵方案临床妊娠率高于自然周期组(30.49％vs 27.89％),但差异无统计学意义(P=0.570).结论 供精人工授精周期妊娠率与多因素有关,其中不孕妇女的年龄是影响AID成功率的重要因素.

OBJECTIVE:To investigate the development and characterizations of the hepatocytes isolated from fetal ovine and to determine the effect of hypoxia on their growth and metabolism.METHODS:Fresh hepatocytes were isolated from the liver of fetal ovine at late gestation, cultured in specific media, and exposed to normoxia (21% O2) or hypoxia (2% O2). The cellular characteristics and population purity were identified by immunocytochemistry and flow cytometry (FCM). The effects of hypoxia on cell cycle and apoptosis of the hepatocytes were evaluated by FCM, whereas the cellular ultrastructure changes were examined with a transmission electron microscope.RESULTS:The cell purity of hepatocytes was over 95%. Under hypoxia exposure, the hepatocytes showed a gradual increase in proportion at the S phase and in proliferative index, followed with a compatible increase in apoptosis and progressively decreased cell viability. Additionally, the organelles of the hepatocytes demonstrated dramatic changes, including swelling of mitochondria, disorder in cristae arrangement, expansion of endoplasmic reticulum, and a large number of circular lipid droplets emerging in the cytoplasm.CONCLUSION:Fetal ovine hepatocytes could be primarily cultured in a short-term culture system with a high purity of over 95% and with their preserved original characteristics. Hypoxia could induce changes in ultrastructural and inhibit the proliferation of cultured fetal ovine hepatocytes through apoptotic mechanisms.

It was to study the influence of Wilms tumor suppressor gene (WT1) on ovarian granular cells (GCs) in mice, and the molecular mechanism involved. LV-WT1 short hairpin ribonucleic acid (shRNA) vector was used to downregulate WT1 expression in granular cells (GCs). The effects of WTI on proliferation and apoptosis of GCs were investigated. Western blot and qRT-PCR were used to assay the mRNA and protein expressions of Bax/bcl-2 in GCs transfected with LV-WT1-RNAi. The expression levels of SUZ12, Wnt5a, Wnt11, Wnt4, Wnt3a, Wnt2 mRNA in GCs were also determined. LV-WT1-RNAi significantly reduced WT1 expression, increased apoptosis and inhibited proliferation of GCs. The inhibition of WT1 had no significant effect on the expression of bcl-2 in GCs. The expressions of Wnt2, Wnt4 and Wnt5a were augmented in WT1-knockdown GCs, relative to non-transfected cells. WT1 activation is necessary for maintaining early survival of GCs in follicles via activation of the Wnt/β-catenin signal pathway.

Objective To investigate the inducing factors of the ectopic pregnancy (EP) after assisted reproductive technology (ART). Methods A reproductive review of 1 034 cycles was completed on EP after ART from January 2016 to December 2017. 1 034 cycles were divided into two groups according to infertility reasons:tubal group and non-tubal group. Results Among 1 034 treatment cycles, there were 439 pregnancies achieved (42.46%). The incidence of EP was 6.83% (30/439). However, 29 cases of tubal pregnancy (96.67%) and 1 case of ovarian pregnancy (3.33%). The incidence of EP of tubal group was higher than that of non-tubal group. In the two ways of ART, the incidence of EP of in vitro fertilization-embryo transfer (IVF-ET) was higher than that of intracytoplasmic sperm injection-embryo transfer (ICSI-ET). Conclusion Tubal factor was the major inducing factor for EP after ART treatment.

Background Chlamydia pneumoniae ( C. pneumoniae) is pathogenic to humans, by causing pulmonary inflammation or bronchitis in both adolescents and young adults. However, the molecular signals linking C. pneumoniae components to inflammation remain elusive. This study was to investigate the effect of Chlamydia-specific Cpn0423 of C. pneumoniae on C. pneumoniae -mediated inflammation. Results Cpn0423 was detected outside of C. pneumoniae inclusions, which induced production of several cytokines including macrophage inflammatory protein-2 (MIP-2) and interleukins (ILs). Production of the Cpn0423-induced cytokines was markedly reduced in cells pretreated with NOD2-siRNA, but not with negative control oligonucleotides. Mice treated with Cpn0423 through intranasal administration exhibited pulmonary inflammation as evidenced by infiltration of inflammatory cells, increased inflammatory scores in the lung histology, recruitment of neutrophils and increased cytokines levels in the BALF. Conclusion Cpn0423 could be sensed by NOD2, which was identified as an essential element in a pathway contributing to the development of C. pneumoniae -mediated inflammation.

Objective:To explore the effective,economical and personalized protocol for infertile patients with poor ovarian response(POR),via comparing treatment outcomes of different controlled ovarian stimulation protocols in assisted reproductive technology.Methods:Three hundred and two clinical cases of POR patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were recruited in this study.According to the different ovarian stimulation protocols,these patients were divided into four groups:43 cycles treated with ultra-short protocol,30 cycles treated with short protocol,62 cycles treated with mini-stimulation protocol of clomiphene combined human menopausal gonadotropin and 167 cycles treated with progestin-primed ovarian stimulation of human menopausal gonadotropin combined medroxy-progesterone acetate in follicular phase.To compare retrospectively the controlled ovarian stimulation response,cycle cancellation and each starting period clinical outcome among the four groups.Results:①There were significant differences in the duration and the total doses of gonadotropin(Gn),medicine fee,the advantage follicle numbers in trigger days,oocytes retrieved rate and Cost-effective(P＜0.05)among the four groups.Ultra-short protocol had the most duration and dose of Gn and were more expensive in medicine price generally.Short protocol had the most expensive in medicine fee to complete a treatment cycle,the advantage follicle numbers in trigger days,and the worst cost-effective to get a viable embryo.Mini-stimulation protocol had the least duration and dose of Gn,dominant follicle numbers in trigger days and oocytes retrieved rate.Human menopausal gonadotropin combined medroxy-progesterone acetate in follicular phase had the most oocytes retrieved rate and the best cost-effective.②In cycle cancelation,due to abnormal fertilization and un-fertilization,none cleavage and viable embryo to cancel cycles were no statistical difference among the four groups(P ＞0.05).Compared with the two groups of short protocol and human menopausal gonadotropin combined medroxy-progesterone acetate in follicular phase,the two groups of mini-stimulation protocol and ultra-short protocol had a higher rate of non-oocyte retrieved per cycle,and the difference was statistically significant(P ＜0.05).③There was no statistically significant difference in the clinical pregnancy rate per oocyte retrieved and implantation rate(P ＞0.05).Human menopausal gonadotropin combined medroxy-progesone acetate in follicular phase had a lower abortion rate compared with mini-stimulation protocol,and a higher ongoing pregnancy rate per oocyte retrieved,in addition,there was statistically significant difference (P ＜ 0.05).Conclusions:Progestin-primed ovarian stimulation of human menopausal gonadotropin combined medroxy-progesterone acetate in follicular phase may be an economic,effective treatment,and is helpful for the poor ovarian response infertile patients.

Objective To investigate imprinting effects of maternal high-salt diet during pregnancy on the function of mesenteric vessels in adult male offspring rats and their possible mechanism.Methods Pregnant Sprague-Dawley rats were randomly assigned to the high-salt group and control group (n=8 in each group).Rats in the high-salt group were given food containing 8％ sodium chloride (NaCl) during pregnancy (D1-21),while the control group was given food with 1％NaCl.All pregnant rats had free access to normal water.All offsprings received breast-feeding,while all mother rats were given normal food and water.Plasma of male offspring at neonatal and adolescent period (two days and 18-20 weeks after birth) were collected,Angiotensin Ⅱ (Ang Ⅱ),plasma renin activity (PRA) and anti-angiotensin type 1 receptor autoantibodies (AT1-AA) were measured.Mesenteric arteries of the offspring male rats were obtained for vascular function and electrophysiological tests to examine the effects of renin-angiotensin system on contractile function of blood vessels and the role of potassium ion (K+) channels in smooth muscle cells.Two-way ANOVA test was used for statistical analysis.Results (1) Plasma Ang] level in high-salt newbom group was lower than in control group [(15.06±2.77) vs (21.33± 1.81) ng/L,P＜0.05],while there was no difference in the Ang Ⅱ,PRA and serum AT1-AA levels between the two adult male offspring groups.(2) Ang Ⅱ (of 10-8.5-10-5 mol/L) induced-vasoconstriction in high-salt group was higher than in control group.AT1 inhibitor Losartan could inhibit most of Ang Ⅱ induced-vasoconstriction,while AT2 inhibitor PD12331 had little effect.(3) Ang Ⅱ was able to inhibit whole-cell K+ current in both groups,but the inhibitory effect was more obvious in high-salt group.Losartan could partially block the inhibitory effect ofAng Ⅱ on the whole-cell K+ current in the two groups,while the AT2 blocker PD12331 (10-5 mol/L) could not at all.Conclusions Mesenteric artery of male offspring rats from the maternal high-salt diet during pregnancy is significantly sensitive to Ang Ⅱ-induced vasoconstrictions,and is related to stronger suppression of the whole-cell K+ current by Ang Ⅱ in high-salt offspring rats.High-salt diet during pregnancy could increase the risk of hypertension in adult male offspring rats.

Objective To study the relationship between the rate of human normal morphology sperm and the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) treatment.MethodsThis study retrospectively analyzed 323 IVF-ET cycles. Sperm morphology was evaluated strictly according to the WHO criterion. Based on the results of morphological evaluation, the 323 cycles were divided into three groups, which deifned morphologically normal sperm≥1% and﹤2.5% as group A,≥2.5% and﹤4% as group B, and≥4% as group C respectively. The relationship between sperm morphology and the rates of fertilization, cleavage, quality embryos, implantation, clinical pregnancy were compared and analyzed among these three groups.Results There was no signiifcant difference among the three groups in female age, infertile years, male age (P﹥0.05). No statistically signiifcant differences were observed in the rates of multi-PN fertilization, cleavage, embryo quality, high quality embryos, implantation, clinical pregnancy (P﹥0.05). Meanwhile, there was statistically signiifcant difference in the rate of fertilization among the three groups (P﹤0.05), following with increase of rate of normal morphology sperm, the fertilizaton was signiifcantly increased.Conclusion Sperm morphology affects the fertility rate of IVF-ET, however, has no signiifcant impact on embryo quality and clinical outcomes of IVF-ET.

SCOPE:High-salt (HS) intake is linked to hypertension, and prenatal exposure to maternal HS diets may have long-term impact on cardiovascular systems. The relationship between HS diets and cardiovascular disease has received extensive attention. This study determined pressor responses and microvessel functions in the adult offspring rats exposed to prenatal HS. METHODS AND RESULTS:The offspring of 5-month old as young adults in rats were used. Blood pressure, vascular tone, intracellular Ca(2+), and BK channels in mesenteric arteries were measured in the offspring. Phenylephrine (Phe)-induced pressor responses were significantly higher in the prenatal HS offspring. Vessel tension and intracellular Ca(2+) concentrations associated with Phe-induced pressor responses were increased in the mesenteric arteries of the HS offspring. PKC α- and δ-isoforms were upregulated in mesenteric arteries of the HS offspring. The enhanced Phe-mediated vascular activity was linked to the altered PKC-modulated BK channel functions. CONCLUSION:The results suggested that prenatal exposure to HS altered microvascular activity probably via changes in PKC/BK signaling pathways, which may lead to increased risks of hypertension in the offspring.

Antenatal malnutrition could be linked to hypertension and vascular diseases in fetal origins. This study determined the influence of maternal intake of high sucrose (HS) during pregnancy on vessel tone, intracellular Ca(2+) ([Ca(2+)](i)), K(+) channels, especially large-conductance Ca(2+)-activated K(+) channels (BK), in mesenteric arteries in the offspring rats exposed to prenatal HS. Vessel tension and [Ca(2+)](i) induced by angiotensin II were higher in the small mesenteric arteries of the HS offspring. In the vascular smooth muscle cells (VSMCs) from the HS offspring, electrophysiological studies showed depressed BK current density and depolarized membrane. Western blot showed altered expressions of BK α-subunits, AT1 and AT2 receptors in mesenteric arteries. The results suggest that decreased BK channel activity and depolarized membrane potential in the VSMCs partly contributed to the increased vessel tone and [Ca(2+)](i) in the HS offspring, adding new information for understanding mechanisms in vascular malfunctions in fetal origins, and novel insights for early prevention and treatments against such vascular diseases.