Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

Modified halloysite nanotubes reduce the toxic effects of zearalenone in gestating sows on growth and muscle development of their offsprings

Background： Zearalenone （ZEN） is an estrogenic mycotoxin that is primarily produced by Fusarium fungi and has been proven to affect the reproductive capacity of many species to varying degrees. The present experiment was designed to study the maternal persistent effects of zearalenone toxicity in gestating sows on growth and muscle development of their offsprings, and the alleviation of zearalenone toxicity by modified halloysite nanotubes （MHNTs）. Methods： Eighteen sows were fed with one of three dietary treatments that included the following： （1） a control diet, （2） a contaminated grain diet （with 50 % moldy corn, 2.77 mg/kg ZEN）, and （3） a contaminated grain diet （with 50 % moldy corn, 2.76 mg/kg ZEN） ＋ 1% MHNTs. Each sow was exclusively fed its experimental diets from 35 to 70 d of gestation at a total of 2 kg daily. Muscle samples were collected from six piglets per treatment at birth, weaning and finishing. Results： The results showed that feeding the sows with the ZEN-contaminated diets from 35 to 70 d of gestation decreased the ADG, ADFI and G：F of their offsprings （P 〈 0.05）. The muscle fiber numbers in the newborn, weaning and growing-finishing pigs and the muscle fiber diameters at birth and weaning were also decreased by maternal ZEN exposure （P 〈 0.05）. The expressions of IGF-I, IGF-II, Myf-5 and Mstn at birth and IGF-II, Pax7, Myf-5 and MyoD1 at weaning were altered by feeding gestating sows with ZEN-contaminated diets （P 〈 0.05）. The MHNTs reduced most of the ZEN-induced toxic effects： the ADG and ADFI on growth performance, the muscle fiber numbers at weaning and finishing and the muscle fiber diameters at weaning （P 〈 0.05）. The expression levels of IGF-II and Mstn in newborn piglets and IGF-II and Myf-5 in weaning piglets were also prevented by adding 1% MHNTs （P 〈 0.05）. Conclusions： The present study demonstrated that the offsprings of sows fed with ZEN-contaminated diets from 35 to 70 day of gestation exhibited weakening on growth performance, physiological changes in their muscle fibers and alterations of mRNA expression in their muscle tissues, and also indicated that MHNTs prevented most of the ZEN- induced weakening in the muscle tissues.

Analysis of the Offspring Sex Ratio of Chicken by Using Molecular Sexing

The overall sex ratio of offspring （dead embryos and hatch chicks） from all the fertilized eggs of 140 hens collected for 30 days was studied using duplex PCR of certain fragments of sex chromosomes. Additional 894 dead embryos over a period of 21 days of incubation were also investigated to verify the sex ratio of the dead embryos. The sex of the early dead embryos was identified using this molecular sexing technique. The sex ratio of the hatch chicks and the total offspring of the hens investigated in this experiment did not differ from the expected sex ratio （i.e., 1：1）., However, the number of female dead embryos was significantly more than that of males. The data indicated that the different physiologic function of males and females contributed to female-biased mortality during incubation. It was also found by further analysis that the sex ratios of the offspring of some hens were significantly biased to female or male over the period investigated, which suggested that the sex ratio of offspring might be influenced by the maternal condition to some degrees.

Enriched environment for offspring improves learning and memory impairments induced by sevoflurane exposure during the second trimester of pregnancy

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and memory of offspring.Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and memory of rat offspring remains unclear.In this study,rats at 14 days of pregnancy were exposed to 3.5%sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days.We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue,increased hippocampal neurogenesis,inhibited glycogen synthase kinase 3βactivity,and increased the expression of cell proliferation-relatedβ-catenin and apoptosis-related Bcl-2,indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus.These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and memory of offspring.This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018PS07K)on January 2,2018.

Maternal Separation Affects Mothers’ Affective and Reproductive Behaviors as Well as Second Offspring’s Emotionality

Daily separation of rat pups from their mothers while the preweaning period has an impact on behavior and stress response of pups. We hypothesized that maternal separation may create a depression-like state in mother rats from which we separate the rat pups and decrease their reproductive function and fertility. Also, we aimed to evaluate the transmission degree of depression and anxiety across generations. Females aged 3 months were divided in two groups of 10 rats each. After a first mating and a first parturition, we conducted maternal separation 3 h during 22 days for the experienced group while the control group mothers kept their pups. At 4 months of age, females underwent behavioral tests and a second mating. Second generation’s pups were also subjected to behavioral tests. Behavioral tests showed that mothers which experienced separation were more depressive and anxious than control ones, also they had a lower litter size. Rats pups of the second generation whose mothers experienced maternal separation also revealed behavior changes akin to depression and anxiety. Thus, maternal separation causes depressive and anxious-likestates on mother rats which experienced separation and has an impact on their litter size. Also, consequences of maternal separation seem to last throughout generations.

Transfer of β-hydroxy-β-methylbutyrate from sows to their offspring and its impact on muscle fiber type transformation and performance in pigs

Background： Previous studies suggested that supplementation of lactating sows with β-hydroxy-β-methylbutyrate（HMB） could improve the performance of weaning pigs, but there were little information in the muscle fiber type transformation of the offspring and the subsequent performance in pigs from weaning through finishing in response to maternal HMB consumption. The purpose of this study was to determine the effect of supplementing lactating sows with HMB on skeletal muscle fiber type transformation and growth of the offspring during d 28 and180 after birth. A total of 20 sows according to their body weight were divided into the control（CON, n = 10） or HMB groups（HMB, n = 10）. Sows in the HMB group were supplemented with β-hydroxy-β-methylbutyrate calcium（HMB-Ca） 2 g/kg feed during d 1 to 27 of lactation. After weaning, 48 mixed sex piglets were blocked by sow treatment and fed standard diets for post-weaning, growing, finishing periods. Growth performance was recorded during d 28 to 180 after birth. Pigs were slaughtered on d 28（n = 6/treatment） and 180（n = 6/treatment） postnatal and the longissimus dorsi（LD） was collected, respectively.Results： The HMB-fed sows during lactation showed increased HMB concentration（P ＆lt; 0.05） in milk and LD of weaning piglets（P ＆lt; 0.05）. In addition, offsprings in HMB group had a higher finishing BW and lean percentage than did pigs in CON group（P ＆lt; 0.05）, meanwhile, compared with pigs from sows fed the CON diet, pigs from sows fed HMB diet showed higher type Ⅱ muscle fiber cross-sectional area（CSA）, elevated myosin heavy chain（MyHC） Ⅱb and Sox6 mRNA, and fast-MyHC protein levels in LD（P ＆lt; 0.05）.Conclusions： HMB supplemented to sow diets throughout lactation increases the levels of HMB in maternal milk and skeletal muscle of pigs during d 28 after birth and promotes subsequent performance of pigs between d 28 and 180 of age by enhancing glycolytic muscle fiber transformation.

Microglia activation in the offspring of prenatal Poly I:C exposed rats:a PET imaging and immunohistochemistry study

Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.

Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring

Mild intrauterine hypoperfusion(MIUH)is a serious pathological event that affects the growth and development of fetuses and offspring.MIUH can lead to growth restriction,low birth weight,neurodevelopmental disorders,and other adverse clinical outcomes.To study the effects of MIUH on learning and memory function in offspring,a model of MIUH was established by placing a coil(length 2.5 mm,diameter 0.24 mm)on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17).Next,120 mg/kg lithium chloride(the MIUH+Li group)or normal saline(the MIUH group)was injected intraperitoneally into these rats.In addition,120 mg/kg lithium chloride(the Li group)or normal saline(the SHAM group)was injected intraperitoneally into pregnant rats without coil placement.The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth.In the MIUH group,the escape latency and journey length before reaching the platform were both increased,and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group.Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins)expression was significantly downregulated in the MIUH group compared with the SHAM group.Furthermore,western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats,and revealed that glycogen synthase kinase 3β(GSK3β)expression was upregulated andβ-catenin expression was downregulated in the MIUH group compared with the SHAM group.In addition,compared with the MIUH group,the expression levels of p-GSK3βandβ-catenin were upregulated in the MIUH+Li group.These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3βsignaling pathway.The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018 PS07 K)in June 2018.

Non-alcoholic fatty liver disease and the impact of genetic,epigenetic and environmental factors in the offspring

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and is strongly associated with metabolic deregulation.More recently,a significant impact of parental NAFLD in the offspring was demonstrated and has been widely discussed.However,pathogenetic pathways implicated in the inheritance by the offspring and relatives are still under debate.Probably,multiple mechanisms are involved as well as in NAFLD pathogenesis itself.Among the multifactorial involved mechanisms,genetic,epigenetic and environmental backgrounds are strongly related to NAFLD development in the offspring.Thus,based on recent evidence from the available literature concerning genetic,epigenetic and environmental disease modifiers,this review aimed to discuss the relationship between parental NAFLD and its impact on the offspring.

Maternal obesity exacerbates the responsiveness of offspring BALB/c mice to cow's milk protein-induced food allergy

Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.

Influence of environmental enrichment on hippocampal synapses in adolescent offspring of mothers exposed to prenatal stress

Environmental enrichment attenuates hippocampal synaptic injury induced by prenatal stress in offspring. However, the influence of hippocampal synaptic changes and regional differences in prenatal stress remains poorly understood. The present study induced stress in Sprague Dawley rats, which were at gestational age 13-19 days. Following weaning, the offspring were raised in an enriched environment to establish models of stress ＋ enriched environment. Dendritic spine density and synaptophysin expression were detected in hippocampal neurons using Golgi staining and western blot analysis, respectively. Results showed that enriched environment increased dendritic spine density of apical dendrites in CA1 pyramidal cells and basal dendrites of granular cells in the outer layer of the dentate gyrus. In addition, hippocampal synaptophysin expression increased and the effects of prenatal stress on neuronal dendritic spines were reversed in adolescence.

Association of nutrients intake during pregnancy with the risk of allergic disease in offspring:a meta-analysis of prospective cohort studies

To investigate the role of nutrients intake during pregnancy with longitudinal development of rhinitis,asthma,eczema,wheeze,and food allergy in offspring.The PubMed,Embase,and Cochrane library were searched for articles published throughout May 2022.The pooled effect estimate were presented using relative risk and calculated by the random-effects model.Twenty-three prospective cohort studies enrolling 210817 individuals were included.The risk of wheeze in offspring were lowered when high vitamin D,vitamin E,zinc,and milk intakes during pregnancy,whereas high meat intake during pregnancy could induce additional risk of wheeze in offspring.Moreover,highβ-carotene and magnesium intakes during pregnancy were related to lower eczema risk in offspring,whereas eczema risk in offspring was increased for pregnant women with high intake of butter and margarine.Finally,the asthma risk in offspring could protect against for pregnant women with high intake of vitamin D and apple,whereas high folic acid during pregnancy could produce excess asthma risk in offspring.This study provides the summary evidences regarding the role of nutrients intake during pregnancy and subsequent risk of rhinitis,asthma,eczema,wheeze,and food allergy,and further effective intervention strategies should be employed to improve childhood allergic diseases.

The effects of inactivated SARS-CoV-2 vaccination and subsequent infection of pregnant mice on the behaviors of offspring

The mass inoculation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019(COVID-19).Pregnant women are prone to a higher risk of COVID-19,and maternal infection is a risk fac-tor for a range of neurological disorders leading to abnormal behavior in adulthood.However,there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood.In this study,human angiotensin-converting enzyme 2 pregnant mice(F0 generation)were immunized with CoronaVac and then infected with SARS-CoV-2.Subsequently,we analyzed the behavioral cognition of their adult offspring(F1 gen-eration)using the open-field test and Morris water maze test.The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial refer-ence memory.

Breeding of Leptin Receptor Gene Knockout Mice and Genotype Identification of the Offspring

The leptin（ LP） receptor gene heterozygous mice were mated in four ways. Genomic DNA was extracted from offspring tails and analyzed by PCR. The result showed that the ratios of the offspring genotypes fit the Mendel＇s laws. The male and female LP^（-/-）mice（ DB / DB mice） were infertile. LP^（-/-）mice could be effectively bred by mating of male and female LP^（＋/-）mice. PCR methods could identify LP^（-/-）mice precisely.

Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells

BACKGROUND The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated.AIM To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring.METHODS Four-week-old female C57BL/6N mice were fed by deficient,low,normal and excessive calcium reproductive diets throughout pregnancy and lactation.Bone MSCs(BMSCs)were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway.The other weaning male pups were fed a high-fat diet for 16 wk,along with normalfat diet as the control.Then the serum was collected for the measurement of biochemical indicators.Meanwhile,the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration.And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction.RESULTS Compared with the control group,maternal deficient,low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity,with larger adipocytes,more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation(PPARγ,C/EBPα,Fabp4,LPL,Adiponectin,Resistin and/or Leptin)among their male offspring(P<0.05).And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro,respectively(P<0.05).Meanwhile,it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups.CONCLUSION Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring,with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.

The Development of Metabolic Derangement in Male Offspring after Perinatal Exposure to Di-(2-Ethylhexyl) Phthalate

The prevalence of obesity and type 2 diabetes mellitus（T2DM）has been increasing throughout the world over the past 20 years.Environmental chemicals known to regulate the endocrine system have been considered as a risk factor for the development of metabolic diseases.Several people are exposed to environmental chemicals during their lives.

The Handan Offspring Myopia Study

The Handan Offspring Myopia Study(HOMS),whose participants came from 6 villages where all people aged≥30 years had taken part in the Handan Eye Study(HES)in 2006-2007,was designed to obtain the familial associations of myopia between parents and their offspring.From March 2010 to June 2010,of 1,238 eligible individuals,878 children(70.2%;52.6%male)from 541 families were recruited.The mean age of the children was 10.5±2.5 years.All the participants had a detailed eye examination and anthropometry examination.All examinations were performed using the same protocols and equipment in both HES and HOMS.Information of the parents was obtained from the HES.The results of the research showed that the myopic shift from parents to children was estimated to be approximately 1 D at 18 years of age.For near work and myopia,no association was found,except for the high near work subgroup with moderate outdoor activity levels.Besides a weak protective effect of outdoor activity on myopia in these rural children was observed.In the future,we plan to follow up these participants and investigate how the refraction of the children change,how myopia-genic activity changes and what effect does it have on myopia.The information will be important for the design of strategies to prevent and reduce myopia.

The Handan Offspring Myopia Study (HOMS): an overview

The Handan Offspring Myopia Study(HOMS)is the first offspring eye study in a Chinese population.The study design is based on another representative study,Handan Eye Study.In this study,we found 1 diopter(D)of generational myopic shift,a weak protective effect of the outdoor activity on myopia,and a modest protective effect of the eye exercises of acupoints on myopia,among the rural children in the northern area.

Effects of dexmedetomidine on developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy

Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant female Sprague-Dawley(SD)rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of dexmedetomidine 100 mL),with 6 rats in each group.On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western blot.The mRNA expressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring rats were detected by real-time RT-PCR.The protein expressions of GAP-43 and nNOS were tested by immunohistochemistry and Western blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNA and protein expressions GAP-43 and nNOS.