Cardiovascular Dysfunction in Offspring of Ovarian-Hyperstimulated Women and Effects of Estradiol and Progesterone: A Retrospective Cohort Study and Proteomics Analysis

Xu, Gufeng; Zhang, Junyu; Pan, Haitian; Shen, Tian; Liu, Miao‐E; Yu, Tiantian; Li, Jingyi; Ying, Wei-Wen; Yao, Weimiao; Lin, Xian-Hua; Lv, Yuan Yuan; Su, Wen-Wen; Ye, Xiaoqun; Zhang, Fanghong; Pan, Jiexue; Liu, Ye; Zhou, Chuanpeng; Zhang, Dan; Liu, Xinmei; Zhu, Yu; Sheng, Jian‐Zhong; Huang, He‐Feng

doi:10.1210/jc.2014-2349

Cited by 48 publications

(41 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a different study conducted in China, researchers did not observe any differences in systemic blood pressure or carotid IMT [43]. However, they did observe significant differences in FMD, carotid systolic and diastolic diameter, diastolic function parameters, and heart rate.…”

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 97%

See 1 more Smart Citation

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Vrooman

Bartolomei

2017

Reproductive Toxicology

View full text Add to dashboard Cite

Millions of children have been born worldwide though assisted reproductive technologies (ART). Consistent with the Developmental Origins of Health and Disease hypothesis, there is concern that ART can induce adverse effects, especially because procedures coincide with epigenetic reprogramming events. Although the majority of studies investigating the effects of ART have focused on perinatal outcomes, more recent studies demonstrate that ART-conceived children may be at increased risk for postnatal effects. Here, we present the current epidemiological evidence that ART-conceived children have detectable differences in blood pressure, body composition, and glucose homeostasis. Similar effects are observed in the ART mouse model, which have no underlying infertility, suggesting that cardiometabolic effects are likely caused by ART procedures and not due to reasons related to infertility. We propose that the mouse system can, consequently, be used to adequately study, modify, and improve outcomes for ART children.

show abstract

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 97%

“…Several studies have reported subclinical but significant cardiovascular changes in ART children (Table 1) [31–43]. In some of the first reports, systemic blood pressure levels were higher in IVF and ICSI children by comparison with children that were conceived spontaneously [31,33].…”

Section: Evidence That Art Can Increase the Risk Of Cardiometabolimentioning

confidence: 99%

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Vrooman

Bartolomei

2017

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…The long term health of their children is well worth studying. Our previous work reported that maternal excessive estrogen exposure before pregnancy might predispose offspring to cardiovascular dysfunction (Xu et al, 2014). Here, we provide evidence that pregestational hyperandrogenism may induce alteration of glucose metabolism in offspring.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundExcessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells.MethodsOf 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5 years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established.FindingsChildren born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16–13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets.InterpretationPregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance.Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.

show abstract

“…The Ingenuity Pathway Analysis (IPA) (Qiagen, Valencia, CA, USA) was used to identify the top biological functions and canonical pathways associated with the differentially expressed mRNAs and miRNAs datasets, as described previously [30]. The Fisher's exact test was used to determine the probability that each biological function or canonical pathway assigned to the dataset is explained by chance alone.…”

Section: Functional Analysis and Paired Mirna-mrna Analysismentioning

confidence: 99%

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

Ding

Guo

Zhang

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

show abstract

Cardiovascular Dysfunction in Offspring of Ovarian-Hyperstimulated Women and Effects of Estradiol and Progesterone: A Retrospective Cohort Study and Proteomics Analysis

Abstract: Children born to ovarian-hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.

Cited by 48 publications

References 33 publications

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

Contact Info

Product

Resources

About