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1.
Front Endocrinol (Lausanne) ; 12: 775233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795643

RESUMO

Traditionally, the anteroventral periventricular (AVPV) nucleus has been the brain area associated with luteinizing hormone (LH) surge secretion in rodents. However, the role of the other population of hypothalamic kisspeptin neurons, in the arcuate nucleus (ARC), has been less well characterized with respect to surge generation. Previous experiments have demonstrated ARC kisspeptin knockdown reduced the amplitude of LH surges, indicating that they have a role in surge amplification. The present study used an optogenetic approach to selectively stimulate ARC kisspeptin neurons and examine the effect on LH surges in mice with different hormonal administrations. LH level was monitored from 13:00 to 21:00 h, at 30-minute intervals. Intact Kiss-Cre female mice showed increased LH secretion during the stimulation period in addition to displaying a spontaneous LH surge around the time of lights off. In ovariectomized Kiss-Cre mice, optogenetic stimulation was followed by a surge-like secretion of LH immediately after the stimulation period. Ovariectomized Kiss-Cre mice with a low dose of 17ß-estradiol (OVX+E) replacement displayed a surge-like increase in LH release during period of optic stimulation. No LH response to the optic stimulation was observed in OVX+E mice on the day of estradiol benzoate (EB) treatment (day 1). However, after administration of progesterone (day 2), all OVX+E+EB+P mice exhibited an LH surge during optic stimulation. A spontaneous LH surge also occurred in these mice at the expected time. Taken together, these results help to affirm the fact that ARC kisspeptin may have a novel amplificatory role in LH surge production, which is dependent on the gonadal steroid milieu.

2.
Front Med (Lausanne) ; 8: 705943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646839

RESUMO

Purpose: To estimate whether the city-specific lockdown in Shanghai induced by the COVID-19 pandemic affected preterm birth rates among uninfected pregnant women in different trimesters. Methods: The population-based retrospective cohort study was conducted in the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai, China. Pregnant women without COVID-19 received perinatal healthcare during lockdown (from January 24, 2020 to March 24, 2020) and non-lockdown (from January 24, 2019 to March 24, 2019) period and giving birth to a live infant at IPMCH were enrolled. 1:1 propensity score matching and Inverse probability of treatment weighting were used to evaluate preterm birth (<37 weeks), very preterm birth (<34 weeks), preterm birth with premature rupture of membranes (PROM-PTB), spontaneous preterm birth with intact membranes (S-PTB), and medically induced preterm birth (MI-PTB) between two groups. Results: 8,270 pregnant women were in the lockdown group, and 9,815 were in the non-lockdown group. Pregnant women in second trimester during lockdown had a higher risk of PTB than those during the non-lockdown period [OR: 1.43 (CI 1.01-2.02), ARD: 1.7% (CI 0.04-3.4%), p = 0.045]. Furthermore, pregnant women in third trimester during lockdown had a higher risk of PROM-PTB than those during the non-lockdown period [OR: 1.64 (CI 1.09-2.47), ARD: 0.9% (CI 0.2-1.6%), p = 0.02]; no group differences were found related to rates of VPTB, S-PTB or MI-PTB. Conclusion: In this cohort study in China, we found that there was an increased risk in preterm birth for non-infected women in COVID-19 lockdown who were in their second trimester.

3.
Reproduction ; 162(6): 437-448, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34605773

RESUMO

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

4.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684457

RESUMO

A high maternal triglyceride (mTG) level during early pregnancy is linked to adverse pregnancy outcomes, but the use of specific interventions has been met with limited success. A retrospective cohort study was designed to investigate the impact of gestational weight gain (GWG) on the relationship between high levels of mTG and adverse pregnancy outcomes in normal early pregnancy body mass index (BMI) women. The patients included 39,665 women with normal BMI who had a singleton pregnancy and underwent serum lipids screening during early pregnancy. The main outcomes were adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, cesarean delivery, preterm birth, and large or small size for gestational age (LGA or SGA) at birth. As a result, the high mTG (≥2.05mM) group had increased risks for gestational hypertension ((Adjusted odds ratio (AOR), 1.80; 95% CI, 1.46 to 2.24)), preeclampsia (1.70; 1.38 to 2.11), gestational diabetes (2.50; 2.26 to 2.76), cesarean delivery (1.22; 1.13 to 1.32), preterm birth (1.42, 1.21 to 1.66), and LGA (1.49, 1.33 to 1.68) compared to the low mTG group, after adjustment for potential confounding factors. Additionally, the risks of any adverse outcome were higher in each GWG subgroup among women with high mTG than those in the low mTG group. High mTG augmented risks of gestational hypertension, preeclampsia, preterm birth, and LGA among women with 50th or greater percentile of GWG. Interestingly, among women who gained less than the 50th percentile of GWG subgroups, there was no relationship between high mTG level and risks for those pregnancy outcomes when compared to low mTG women. Therefore, weight control and staying below 50th centile of the suggested GWG according to gestational age can diminish the increased risks of adverse pregnancy outcomes caused by high mTG during early pregnancy.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Resultado da Gravidez , Triglicerídeos/sangue , Adulto , Feminino , Idade Gestacional , Humanos , Gravidez , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Adulto Jovem
5.
Front Endocrinol (Lausanne) ; 12: 710221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531826

RESUMO

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.

6.
Endocrine ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542801

RESUMO

PURPOSE: Adulthood and childhood obesity are both associated with reproductive diseases and gynecological cancers in females. However, the causal factors associated with these observations have yet to be identified. Mendelian randomization is a process that is independent of inverse bias and confounding and can act as a random control trial in which genetic groups are settled during meiosis, thus representing an effective tool with which to investigate causality. METHODS: We carried out several Mendelian randomization trials based on the combined genetic scores of 75 adult-associated and 15 childhood-associated body mass index (BMI) single nucleotide polymorphisms (SNPs), databases for several gynecological cancers and reproductive diseases from the UK Biobank (with 194,153 participants), using the traditional inverse-variance weighted (IVW) method as the main method. RESULTS: Elevated adult-associated BMI scores (odds ratio [OR] = 1.003; 95% confidence interval [CI]: 1.001-1.004) and childhood-associated BMI scores (OR = 1.003; 95% CI: 1.001-1.004) were related to a higher risk of the polycystic ovarian syndrome (PCOS), as determined by the traditional IVW method. The random IVW method further revealed a nominal negative causal association between childhood-associated BMI and subsequent endometriosis (OR = 0.995; 95% CI: 0.991-0.999). CONCLUSIONS: Consistent with observational consequences, our findings indicated that adulthood obesity may play role in the development of PCOS and that childhood obesity can increase the risk of PCOS but may reduce the incidence of endometriosis in later life. Further research is now needed to validate our findings and identify the precise mechanisms involved.

7.
Reprod Sci ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580843

RESUMO

High maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

8.
J Clin Med ; 10(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34501345

RESUMO

BACKGROUND: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. METHOD: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). RESULTS: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03-1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04-1.79). CONCLUSION: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy.

9.
Reprod Biol Endocrinol ; 19(1): 140, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503525

RESUMO

BACKGROUND: There has been increasing interest in the relationship between body mass index(BMI) and pregnancy outcomes, especially in women undergoing frozen embryo transfer(FET). Several observational studies have been published, but so far with conflicting results. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Pubmed, Embase, Cochrane Library, Clinicaltrails.gov and Web of Science databases were searched based on established search strategy from inception through January 2021. RESULTS: Twelve studies were eligible. In women following FET, high BMI (BMI ≥ 23 kg/m2) was associated with an impaired live birth rate (LBR, OR: 0.89, 95% CI: 0.82-0.96, P = 0.002), but wasn't associated with the implantation rate or the clinical pregnancy rate. Subgroup analysis revealed higher LBR for women didn't complicated by polycystic ovary syndrome (PCOS, OR: 0.96, 95% CI: 0.85-1.08, P = 0.46) and women with blastocyst transferred (OR: 0.89, 95% CI: 0.68-1.16, P = 0.40). LBR did not differ between the low BMI group (BMI < 18.5 kg/m2) and the normal weight group. CONCLUSIONS: Our study showed that high BMI in women is negatively associated with LBR in FET cycles, whereas low BMI isn't. The results of subgroup analysis implied a need for women with a high BMI to get individualized weight management and treatment. Further evidence is still required to optimize preconception health and develop Nutritional and exercise guidelines.

10.
Int J Environ Health Res ; : 1-11, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496690

RESUMO

We tested the hypothesis of whether maternal residential proximity to municipal solid waste incinerator (MSWI) sites could significantly affect birth outcomes. This retrospective birth cohort study conducted at the International Peace Maternity and Infant Hospital, Shanghai, China, included 59,606 mothers with singleton live births during 2014-2018. Multivariate generalized linear models were used to examine associations between residential proximity to MSWI sites and birth outcomes. Small for gestational age (SGA) was significantly more common among children with maternal residential proximity to MSWI sites (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.07-1.34). Maternal prepregnancy body mass index (BMI) influenced this association. Infants of underweight mothers (prepregnancy BMI <18.5 kg/m2) with MSWI exposure (OR=2.00, 95% CI: 1.58-2.52) had higher risks of SGA than their counterparts. Our findings underscore the need to prevent adverse environmental effects of MSWI on birth outcomes; improved exposure assessment measures are warranted in future studies.

11.
Front Endocrinol (Lausanne) ; 12: 706369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367073

RESUMO

Purpose: While it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation). Methods: A large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight. Results: Advanced paternal age was associated with a higher risk for a preterm birth [35-44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35-44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35-44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35-44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery. Conclusions: Our study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.

12.
Front Pediatr ; 9: 654596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368025

RESUMO

Background: Elevated intrapartum temperature has been widely proven to be associated with adverse clinical outcomes in both mothers and neonates. Histological chorioamnionitis (HCA), the inflammation of chorion and amniotic membranes, is commonly observed in those with elevated intrapartum temperature. Thus, we aimed to explore whether the combination of HCA would further affect the pregnancy outcomes in those with intrapartum temperature ≥ 37.5°C. Methods: This retrospective cohort study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH), including all full-term women with intrapartum temperature ≥ 37.5°C from Jan 2017 to Jan 2019. Patients were divided in to HCA group or control group according to placental pathology results, and we used 1:1 propensity score matching (PSM) to reduce the effects of potential confounding factors between the two groups. Univariate and multivariable logistic regression were used to identify the association between HCA and different adverse maternal and neonatal outcomes. Results: We formed a propensity-score matched cohort containing 464 women in each group. Higher positive rate of mycoplasma (14.01% vs. 7.33%, p = 0.001) was found in the vaginal secretion culture of women in the HCA group. After adjusting for various baseline clinical characteristics, women with HCA were more likely to end their delivery by cesarean section (AOR = 1.55, 95% CI: 1.05-2.28), and puerperal morbidity (AOR = 2.77, 95% CI: 1.44-5.33) as well as prolonged hospitalization (AOR = 1.56, 95% CI: 1.12-2.17) were more likely to be observed in the HCA group. The existence of HCA might also be associated with neonatal sepsis (AOR = 2.83, 95% CI: 1.14-7.04) and NICU admission (AOR = 1.40, 95% CI: 1.04-1.87) in newborns. In the study on the impact of different stages of HCA, we found that both maternal and neonatal outcomes would not be affected by mild HCA (stage I), while HCA of stage III was associated with increased need for neonatal respiratory support and elevated likelihood of prolonged hospitalization in neonates. Conclusions: Elevated intrapartum temperature complicated by HCA might be related to the elevated occurrence of several adverse maternal and neonatal outcomes, except those with HCA of stage I. Advanced HCA stage correlated with a worse prognosis.

13.
Front Cell Dev Biol ; 9: 694769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336842

RESUMO

Background: Assisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring' later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET). Results: Global methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5'UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B). Conclusions: ART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.

14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(3): 335-344, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34402258

RESUMO

Aberrant maternal inflammation and oxidative stress are the two main mechanisms of pathological pregnancy. The silence information regulator (sirtuin) family is a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases. By regulating the post-translational modification of proteins, sirtuin is involved in various biological processes including oxidative stress and inflammation. Nowadays, emerging evidence indicates that sirtuin may be closely related to the occurrence and development of pathological pregnancy. The down-regulation of sirtuin can cause spontaneous preterm delivery by promoting uterine contraction and rupture of fetal membranes, cause gestational diabetes mellitus through promoting oxidative stress and affecting the activity of key enzymes in glucose metabolism, cause preeclampsia by reducing the proliferation and invasion ability of trophoblasts, cause intrahepatic cholestasis of pregnancy by promoting the production of bile acids and T helper 1 cell (Th1) cytokines, and cause intrauterine growth restriction through inducing mitochondrial dysfunction. Moreover, the expression and activation of sirtuin can be modulated through dietary interventions, thus sirtuin is expected to become a new target for the prevention and treatment of pregnancy complications. This article reviews the role of the sirtuin family in the occurrence and development of pathological pregnancy and its influence on the development of the offspring.


Assuntos
Diabetes Gestacional , Nascimento Prematuro , Feminino , Humanos , Gravidez , Trofoblastos
15.
BMC Pregnancy Childbirth ; 21(1): 586, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429102

RESUMO

BACKGROUND: The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. METHODS/DESIGN: A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. DISCUSSION: To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. TRIAL REGISTRATION NUMBER: ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

16.
Horm Metab Res ; 53(8): 504-511, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34384107

RESUMO

Insulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic ß-cells in obese PCOS women.

17.
Transl Psychiatry ; 11(1): 434, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417446

RESUMO

Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM.


Assuntos
Diabetes Gestacional , Hiperglicemia , Efeitos Tardios da Exposição Pré-Natal , Animais , Diabetes Gestacional/genética , Epigênese Genética , Feminino , Hiperglicemia/complicações , Hiperglicemia/genética , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética
18.
BMJ Open ; 11(8): e053617, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452972

RESUMO

INTRODUCTION: Chromosomal abnormalities and monogenic disorders account for ~15%-25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved. METHODS AND ANALYSIS: This study is a multicentre, prospective study. The participants were recruited from three tertiary hospitals in China starting from 10 April 2021. The study is expected to conclude before 10 October 2022. Pregnant women with abnormal prenatal screening results indicated for invasive prenatal diagnosis or those who decide to terminate their pregnancies due to abnormal ultrasound findings will be evaluated for enrolment. Cell-free DNA extracted from the maternal plasma will be used for an analytically validated comprehensive NIPS test developed by Beijing BioBiggen Technology Co. (Beijing, China). The diagnostic results from prenatal or postnatal specimens as well as the pregnancy outcome data will be collected to examine the clinical sensitivity, specificity, positive and negative predictive values of the test. ETHICS AND DISSEMINATION: This study was approved by the Obstetrics and Gynecology Hospital of Fudan University (2020-178). Results of this study will be disseminated to public through scientific conferences and a peer-reviewed journal. Written informed consents will be obtained from participants. TRIAL REGISTRATION NUMBER: ChiCTR2100045739.


Assuntos
Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Aneuploidia , Feminino , Humanos , Estudos Multicêntricos como Assunto , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos
19.
Med Sci Monit ; 27: e929904, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34230447

RESUMO

BACKGROUND Since China has not yet constructed its own risk assessment model (RAM) for pregnancy-related venous thromboembolism (VTE), more and more hospitals use the RCOG RAM for VTE risk prediction. However, the RCOG RAM was established based on Western populations, and its applicability in China is still uncertain. Thus, we aimed to evaluate the validity of the RCOG RAM in predicting postpartum VTE in Chinese maternity. MATERIAL AND METHODS This retrospective case-control study was conducted at the International Peace Maternity and Child Health Hospital (IPMCHH) from June 2016 to June 2020. The VTE group consisted of 38 women with postpartum VTE. For each VTE patient, 4 women without VTE who gave birth on the same day were randomly selected as the control group (n=152). The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and validity of the RCOG RAM. Univariable analysis and multivariable logistic regression analysis were used to identify other related factors for postpartum VTE. RESULTS Compared with the low-risk group, the risk of VTE was 9.75-fold greater in the intermediate-risk group, and 90.00-fold greater in the high-risk group. The area under curve (AUC) of the model was 0.828 (95% CI: 0.762-0.894), with a score of 2 as its best cut-off value, which exactly matched the criterion recommended by the RCOG guidelines for pharmacological thromboprophylaxis. The calibration curves and DCA of the model also showed good accuracy. In addition to the factors included in the RCOG RAM, glucocorticoid therapy during pregnancy (adjusted OR=6.72, 95% CI: 1.56-28.91) and previous use of IUD (adjusted OR=7.11, 95% CI: 1.45-34.93) were associated with increased risk of postpartum VTE. CONCLUSIONS The RCOG RAM was found to be effective in predicting postpartum VTE, and has certain guiding significance for postpartum thromboprophylaxis in China.

20.
Front Genet ; 12: 689897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211505

RESUMO

Background: Observational studies have implied an association between polycystic ovary syndrome (PCOS) and psychiatric disorders. Here we examined whether PCOS might contribute causally to such disorders, focusing on anxiety disorder (AD), bipolar disorder (BIP), major depression disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). Methods: Causality was explored using two-sample Mendelian randomization (MR) with genetic variants as instrumental variables. The genetic variants were from summary data of genome-wide association studies in European populations. First, potential causal effects of PCOS on each psychiatric disorder were evaluated, and then potential reverse causality was also assessed once PCOS was found to be causally associated with any psychiatric disorder. Causal effects were explored using inverse variance weighting, MR-Egger analysis, simulation extrapolation, and weighted median analysis. Results: Genetically predicted PCOS was positively associated with OCD based on inverse variance weighting (OR 1.339, 95% CI 1.083-1.657, p = 0.007), simulation extrapolation (OR 1.382, 95% CI 1.149-1.662, p = 0.009) and weighted median analysis (OR 1.493, 95% CI 1.145-1.946, p = 0.003). However, genetically predicted OCD was not associated with PCOS. Genetically predicted PCOS did not exert causal effects on AD, BIP, MDD, or SCZ. Conclusions: In European populations, PCOS may be a causal factor in OCD, but not AD, BIP, MDD, or SCZ.

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