The potential role of the E SRRG pathway in placental dysfunction

Zou, Zhiyong; Forbes, Karen; Harris, Lynda K.; Heazell, Alexander E P

doi:10.1530/rep-20-0272

Cited by 13 publications

(5 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a special organ for the communication between the fetus and the mother, the placenta has the functions of material transport, endocrine, and barrier, which are essential for fetal survival and development 87 . The impaired placental function can lead to IUGR 88 , and IUGR individuals exhibit multiple organ dysplasia 89 . It has been shown that some drugs may indirectly induce multi-organ developmental toxicity by affecting the functional development of the placenta.…”

Section: Multi-organ Developmental Toxicity In Offspring Induced By M...mentioning

confidence: 99%

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Guo

et al. 2023

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Section: Multi-organ Developmental Toxicity In Offspring Induced By M...mentioning

confidence: 99%

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Guo

et al. 2023

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

“…Studies have reported differences in the etiology of early and late-onset preeclampsia [ 41 , 42 ], as well as varying risks of adverse outcomes associated with the timing of exposure [ 43 , 44 ]. Early-onset preeclampsia may be driven by placental dysfunction [ 45 ], which occurs when a placental abnormality restricts blood flow, potentially due to suppression of estrogen-related receptor-gamma leading to vascular abnormalities [ 46 ]. Late-onset preeclampsia could be primarily a maternal hypertensive condition [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study

Carter,

Lin,

Chow

et al. 2024

JMIR Public Health Surveill

View full text Add to dashboard Cite

Background Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. Objective This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. Methods This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. Results Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. Conclusions Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

show abstract

“…Our ultimate aim is to understand the mechanisms underlying placental dysfunction observed in FGR, with a particular focus on the role of ESRRG [ 95 ]. The sex-specific effects of BPA on ESRRG signaling we observed might begin to provide a biological explanation for the observed relationship between low fetal weight in male neonates and maternal BPA exposure seen in epidemiological studies.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta

Zou

Harris

Forbes

et al. 2022

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Bisphenol A (BPA) exposure during pregnancy is associated with low fetal weight, particularly in male fetuses. Expression of estrogen-related receptor gamma (ESRRG), a receptor for BPA in human placenta, is reduced in fetal growth restriction. This study sought to explore whether ESRRG signaling mediates BPA-induced placental dysfunction, and determine whether changes in the ESRRG signaling pathway are sex-specific. Placental villous explants from 18 normal term pregnancies were cultured with a range of BPA concentrations (1 nM-1 μM). Baseline BPA concentrations in the placental tissue used for explant culture ranged from 0.04 nM-5.1 nM (average 2.3 nM ±1.9 nM; n = 6). Expression of ESRRG signalling pathway constituents and cell turnover were quantified. BPA (1 μM) increased ESRRG mRNA expression after 24 hours in both sexes. ESRRG mRNA and protein expression were increased in female placentas treated with 1 μM BPA for 24 hours, but were decreased in male placentas treated with 1 nM or 1 μM for 48 hours. Levels of HSD17B1 and PLAC1, genes downstream of ESRRG, were also affected. HSD17B1 mRNA expression was increased in female placentas by 1 μM BPA; however, 1 nM BPA reduced HSD17B1 and PLAC1 expression in male placentas at 48 hours. BPA treatment did not affect rates of proliferation, apoptosis or syncytiotrophoblast differentiation in cultured villous explants. This study has demonstrated that BPA affects the ESRRG signalling pathway in a sex-specific manner in human placentas and a possible biological mechanism to explain the differential effects of BPA exposure on male and female fetuses observed in epidemiological studies.

show abstract

The potential role of the E SRRG pathway in placental dysfunction

Cited by 13 publications

References 109 publications

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study

Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta

Contact Info

Product

Resources

About