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In vitro fertilization alters phospholipid profiles in mouse placenta.

ABSTRACT: PURPOSE:Studies on humans and rodents have clearly shown that in vitro fertilization (IVF) is associated with abnormal placenta formation and function. Currently, dysregulated placental lipid metabolism is one of the emerging pathogenetic pathways implicated in adverse pregnancy outcomes. The purpose of this study was to identify the effects of IVF on lipid metabolism in the mouse placenta. METHODS:Two groups of mouse placentas, composed of control and IVF, were collected at embryonic day 18.5. Placental lipid profiles were measured using liquid chromatography coupled with mass spectrometry. The relative levels of individual lipid were examined and compared. The proteins and enzymes that regulate the phospholipid biosynthesis were also compared by western blot. RESULTS:A significant increase in levels of phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylglycerols, lysophosphatidylcholines, and mitochondrial cardiolipin were found in the IVF placenta. In addition, proteins and enzymes that regulate the phospholipid biosynthesis were also altered in IVF placentas. CONCLUSIONS:After lipidomic analysis, we present the first detailed overview of the effect of IVF on lipid metabolism, especially phospholipid profiles in the placenta in a mouse model. The widespread lipidomic shifts identified in this study might explicate some of the placental dysfunction observed after IVF, thereby illustrating that phospholipids serve as early warning biomarkers of health risks in IVF offspring.

SUBMITTER: Chen S

PROVIDER: S-EPMC6439083 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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In vitro fertilization alters phospholipid profiles in mouse placenta.

Chen Shuqiang S Wang Jun J Wang Ming M Lu Jie J Cai Yang Y Li Bo B

Journal of assisted reproduction and genetics 20190104 3

<h4>Purpose</h4>Studies on humans and rodents have clearly shown that in vitro fertilization (IVF) is associated with abnormal placenta formation and function. Currently, dysregulated placental lipid metabolism is one of the emerging pathogenetic pathways implicated in adverse pregnancy outcomes. The purpose of this study was to identify the effects of IVF on lipid metabolism in the mouse placenta.<h4>Methods</h4>Two groups of mouse placentas, composed of control and IVF, were collected at embry ...[more]

PMID: 30610659

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Project description:BackgroundThe placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET).MethodsThis study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools.ResultsA total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up- and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo.ConclusionThese data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.

Project description:Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011-2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34-7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42-6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12-10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle.

Project description:IntroductionEmerging evidence has shown that in-vitro fertilization (IVF) is associated with higher risks of certain placental abnormalities or complications, such as placental abruption, preeclampsia, and preterm birth. However, there is a lack of large population-based analysis focusing on placental abnormalities or complications following IVF treatment. This study aimed to estimate the absolute risk of placental abnormalities or complications during IVF-conceived pregnancy.MethodsWe conducted a retrospective cohort study of 16 535 852 singleton pregnancies with delivery outcomes in China between 2013 and 2018, based on the Hospital Quality Monitoring System databases. Main outcomes included placental abnormalities (placenta previa, placental abruption, placenta accrete, and abnormal morphology of placenta) and placenta-related complications (gestational hypertension, preeclampsia, eclampsia, preterm birth, fetal distress, and fetal growth restriction (FGR)). Poisson regression modeling with restricted cubic splines of exact maternal age was used to estimate the absolute risk in both the IVF and non-IVF groups.ResultsThe IVF group (n = 183 059) was more likely than the non-IVF group (n = 16 352 793) to present placenta previa (aRR: 1.87 [1.83-1.91]), placental abruption (aRR: 1.16 [1.11-1.21]), placenta accrete (aRR: 2.00 [1.96-2.04]), abnormal morphology of placenta (aRR: 2.12 [2.07 to 2.16]), gestational hypertension (aRR: 1.55 [1.51-1.59]), preeclampsia (aRR: 1.54 [1.51-1.57]), preterm birth (aRR: 1.48 [1.46-1.51]), fetal distress (aRR: 1.39 [1.37-1.42]), and FGR (aRR: 1.36 [1.30-1.42]), but no significant difference in eclampsia (aRR: 0.91 [0.80-1.04]) was found. The absolute risk of each outcome with increasing maternal age in both the IVF and non-IVF group presented two patterns: an upward curve showing in placenta previa, placenta accreta, abnormal morphology of placenta, and gestational hypertension; and a J-shape curve showing in placental abruption, preeclampsia, eclampsia, preterm birth, fetal distress, and FGR.ConclusionIVF is an independent risk factor for placental abnormalities and placental-related complications, and the risk is associated with maternal age. Further research is needed to evaluate the long-term placenta-related chronic diseases of IVF patients and their offspring.

Project description:Prenatal alcohol exposure (PAE) can harm the embryonic development and cause life-long consequences in offspring's health. To clarify the molecular mechanisms of PAE we have used a mouse model of early alcohol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first eight days of gestation (GD 0.5-8.5). Owing to the detected postnatal growth-restricted phenotype in the offspring of this mouse model and both prenatal and postnatal growth restriction in alcohol-exposed humans, we focused on imprinted genes Insulin-like growth factor 2 (Igf2), H19, Small Nuclear Ribonucleoprotein Polypeptide N (Snrpn) and Paternally expressed gene 3 (Peg3), which all are known to be involved in embryonic and placental growth and development. We studied the effects of alcohol on DNA methylation level at the Igf2/H19 imprinting control region (ICR), Igf2 differentially methylated region 1, Snrpn ICR and Peg3 ICR in 9.5 embryonic days old (E9.5) embryos and placentas by using MassARRAY EpiTYPER. To determine alcohol-induced alterations globally, we also examined methylation in long interspersed nuclear elements (Line-1) in E9.5 placentas. We did not observe any significant alcohol-induced changes in DNA methylation levels. We explored effects of PAE on gene expression of E9.5 embryos as well as E9.5 and E16.5 placentas by using quantitative PCR. The expression of growth promoter gene Igf2 was decreased in the alcohol-exposed E9.5 and E16.5 placentas. The expression of negative growth controller H19 was significantly increased in the alcohol-exposed E9.5 embryos compared to controls, and conversely, a trend of decreased expression in alcohol-exposed E9.5 and E16.5 placentas were observed. Furthermore, increased Snrpn expression in alcohol-exposed E9.5 embryos was also detected. Our study indicates that albeit no alterations in the DNA methylation levels of studied sequences were detected by EpiTYPER, early PAE can affect the expression of imprinted genes in both developing embryo and placenta.

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In vitro fertilization alters phospholipid profiles in mouse placenta.

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In vitro fertilization alters phospholipid profiles in mouse placenta.

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