The increased expression of glucose transporters in human full-term placentas from assisted reproductive technology without changes of mTOR signaling

Dong, Jie; Wen, Liang; Guo, Xiangyu; Xiao, Xifeng; Jiang, Feng; Li, Bo; Jin, Ni; Wang, Jingjing; Chen, Shuqiang

doi:10.1016/j.placenta.2019.08.087

Cited by 11 publications

(6 citation statements)

References 46 publications

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“…As to the other transporter systems investigated in this study, we did not observe differences in placental expression levels of GLUT1, P-gp and BCRP transporters in the CON and ICSI groups. Dong et al [ 60 ] found increased levels of GLUT1 in placentae from ART pregnancies, which contrasts with our findings. Such differences may result from patient inclusion criteria in both studies, since the ART group in Dong’s study consisted of pregnancies conceived by IVF and ICSI, delivered both by vaginal and C-section modes [ 60 ], whereas in this report, we only recruited ICSI pregnancies which delivered by C-section with no labor.…”

Section: Discussioncontrasting

confidence: 99%

“…Dong et al [ 60 ] found increased levels of GLUT1 in placentae from ART pregnancies, which contrasts with our findings. Such differences may result from patient inclusion criteria in both studies, since the ART group in Dong’s study consisted of pregnancies conceived by IVF and ICSI, delivered both by vaginal and C-section modes [ 60 ], whereas in this report, we only recruited ICSI pregnancies which delivered by C-section with no labor. Accordingly, we did not find differences in glucose levels in the maternal and venous umbilical cord blood, which matches our findings in placental GLUT1 expression.…”

Section: Discussioncontrasting

confidence: 99%

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Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

et al. 2021

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Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

et al. 2021

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“…Recently, Mani et al also identified female‐biased genome‐wide hypomethylation in mouse and human placentas associated with ART 13 . In support of our findings, PHLDA2 mRNA and protein expression were also significantly downregulated in term human ART placentas compared with placentas from natural pregnancies and associated with upregulated KCNQ1OT1 mRNA; DNA methylation levels at the KCNQ1OT1 ICR showed a decreasing trend in ART placentas 89 . Furthermore, placentas from mouse embryos cultured from the 1‐cell to blastocyst stage exhibited hypomethylation at Kcnq1ot1 , Peg3 and H19/Igf2 ICRs at E18.5 73 .…”

Section: Discussionsupporting

confidence: 88%

Protective and sex‐specific effects of moderate dose folic acid supplementation on the placenta following assisted reproduction in mice

et al. 2022

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Epigenetic defects induced by assisted reproductive technologies (ART) have been suggested as a potential mechanism contributing to suboptimal placentation. Here, we hypothesize that ART perturbs DNA methylation (DNAme) and gene expression during early placenta development, leading to abnormal placental phenotypes observed at term. Since folic acid (FA) plays a crucial role in epigenetic regulation, we propose that FA supplementation can rescue ART‐induced placental defects. Female mice were placed on a control diet (CD), a moderate 4‐fold (FAS4) or high dose 10‐fold (FAS10) FA‐supplemented diet prior to ART and compared to a natural mating group. ART resulted in 41 and 28 differentially expressed genes (DEGs) in E10.5 female and male placentas, respectively. Many DEGs were implicated in early placenta development and associated with DNAme changes; a number clustered at known imprinting control regions (ICR). In females, FAS4 partially corrected alterations in gene expression while FAS10 showed evidence of male‐biased adverse effects. DNAme and gene expression for five genes involved in early placentation (Phlda2, EphB2, Igf2, Peg3, L3mbtl1) were followed up in placentas from normal as well as delayed and abnormal embryos. Phlda2 and Igf2 expression levels were lowest after ART in placentas of female delayed embryos. Moreover, ART concomitantly reduced DNAme at the Kcnq1ot1 ICR which regulates Phlda2 expression; FAS4 partially improved DNAme in a sex‐specific manner. In conclusion, ART‐associated placental DNAme and transcriptome alterations observed at mid‐gestation are sex‐specific; they may help explain adverse placental phenotypes detected at term and are partially corrected by maternal moderate dose FA supplementation.

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“…Thus, aberrant methylation of imprinted genes may be an indicator of more global epigenetic instability ( Denomme and Mann, 2012 ). Specifically, H19/IGF2, LINE-1Hs , ERVFRD-1, and KCNQ1OT1 are affected in ART through changes in placental DNA methylation ( Turan et al, 2010 ; Nelissen et al, 2013 ; Choux et al, 2018 ; Dong et al, 2019 ). Expression of H19 is linked with fetal and placental growth suppression ( Gao et al, 2012 ) and was significantly higher ( Turan et al, 2010 ; Nelissen et al, 2013 , 2014 ; Sakian et al, 2015 ; Chi et al, 2020 ), while IGF2 expression , which increases fetal and placental growth ( Sakian et al, 2015 ; Chi et al, 2020 ) was significantly lower in ART compared with SC placentas ( Nelissen et al, 2014 ; Sakian et al, 2015 ; Chi et al, 2020 ).…”

Section: Intrauterine Mechanisms–placental Programming In Artmentioning

confidence: 99%

The Consequences of Assisted Reproduction Technologies on the Offspring Health Throughout Life: A Placental Contribution

Schroêder

Badini

Sferruzzi‐Perri

et al. 2022

Front. Cell Dev. Biol.

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The use of assisted reproductive technologies (ART) worldwide has led to the conception and birth of over eight million babies since being implemented in 1978. ART use is currently on the rise, given growing infertility and the increase in conception age among men and women in industrialized countries. Though obstetric and perinatal outcomes have improved over the years, pregnancies achieved by ART still bear increased risks for the mother and the unborn child. Moreover, given that the first generation of ART offspring is now only reaching their forties, the long-term effects of ART are currently unknown. This is important, as there is a wealth of data showing that life-long health can be predetermined by poor conditions during intrauterine development, including irregularities in the structure and functioning of the placenta. In the current review, we aim to summarize the latest available findings examining the effects of ART on the cardiometabolic, cognitive/neurodevelopmental, and behavioral outcomes in the perinatal period, childhood and adolescence/adulthood; and to examine placental intrinsic factors that may contribute to the developmental outcomes of ART offspring. Altogether, the latest knowledge about life outcomes beyond adolescence for those conceived by ART appears to suggest a better long-term outcome than previously predicted. There are also changes in placenta structure and functional capacity with ART. However, more work in this area is critically required, since the potential consequences of ART may still emerge as the offspring gets older. In addition, knowledge of the placenta may help to foresee and mitigate any adverse outcomes in the offspring.

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The increased expression of glucose transporters in human full-term placentas from assisted reproductive technology without changes of mTOR signaling

Cited by 11 publications

References 46 publications

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

Protective and sex‐specific effects of moderate dose folic acid supplementation on the placenta following assisted reproduction in mice

The Consequences of Assisted Reproduction Technologies on the Offspring Health Throughout Life: A Placental Contribution

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