Sex differences in microRNA expression in first and third trimester human placenta

Flowers, Amy E; Gonzalez, Tania L.; Joshi, Nikhil; Eisman, Laura E; Clark, Ekaterina L; Buttle, Rae; Sauro, Erica; DiPentino, Rosemarie; Lin, Yayu; Wu, Di; Wang, Yizhou; Santiskulvong, Chintda; Tang, Jie; Lee, Bora; Sun, Tianyanxin; Chan, Jessica; Wang, Erica T.; Jefferies, Caroline A.; Lawrenson, Kate; Zhu, Yazhen; Afshar, Yalda; Tseng, Hsian-Rong; Williams, John W; Pisarska, Margareta D.

doi:10.1093/biolre/ioab221

Cited by 10 publications

(8 citation statements)

References 88 publications

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“…In this context, differentially-expressed miRNAs between males and females were recently reported by examining the transcriptomic datasets available in public databases in respect to their biological characteristics. [102][103][104][105] Our data showed that Mir21a, Mir16-1 and Mir16-2 were specifically induced in females after exposure to TCDD.…”

Section: Discussionmentioning

confidence: 50%

Female‐to‐male differential transcription patterns of miRNA‐mRNA networks in the livers of dioxin‐exposed mice

Hammoudeh

Soukkarieh

Murphy

et al. 2023

Environmental Toxicology

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Non‐coding microRNAs (miRNAs) have important roles in regulating the expression of liver mRNAs in response to xenobiotic‐exposure, but their roles concerning dioxins such as TCDD (2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin) are less clear. This report concerns the potential implication of liver (class I) and circulating (class II) miRNAs in hepatotoxicity of female and male mice after acute exposure to TCDD. The data show that, of a total of 38 types of miRNAs, the expression of eight miRNAs were upregulated in both female and male mice exposed to TCDD. Inversely, the expression of nine miRNAs were significantly downregulated in both animal genders. Moreover, certain miRNAs were preferentially induced in either females or males. The potential downstream regulatory effects of miRNAs on their target genes was evaluated by determining the expression of three group of genes that are potentially involved in cancer biogenesis, other diseases and in hepatotoxicity. It was found that certain cancer‐related genes were more highly expressed females rather than males after exposure to TCDD. Furthermore, a paradoxical female‐to‐male transcriptional pattern was found for several disease‐related and hepatotoxicity‐related genes. These results suggest the possibility of developing of new miRNA‐specific interfering molecules to address their dysfunctions as caused by TCDD.

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Section: Discussionmentioning

confidence: 50%

Female‐to‐male differential transcription patterns of miRNA‐mRNA networks in the livers of dioxin‐exposed mice

Hammoudeh

Soukkarieh

Murphy

et al. 2023

Environmental Toxicology

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“…Gestational-adjusted expression of miR-21 has been reported to be positively associated with GDM 30 . Sexually dimorphic miRNA expression during pregnancy in the human placenta was reported by Amy E. Flowers et al They found that miR361 was differentially expressed and upregulated in women of the 1st and 3rd trimesters 31 . One of the significant points in this research is the results of the binary logistic regression and correlation analysis.…”

Section: Discussionmentioning

confidence: 85%

Analysis of serum circulating MicroRNAs level in Malaysian patients with gestational diabetes mellitus

pour

Zain

Vazifehmand

et al. 2022

Sci Rep

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Gestational diabetes mellitus (GDM) is a severe global issue that requires immediate attention. MicroRNA expression abnormalities are possibly disease-specific and may contribute to GDM pathological processes. To date, there is limited data on miRNA profiling in GDM, especially that involves a longitudinal study. Here, we performed miRNA expression profiling in the entire duration of pregnancy (during pregnancy until parturition and postpartum) using a miRNA- polymerase chain reaction array (miRNA-PCRArray) and in-silico analysis to identify unique miRNAs expression and their anticipated target genes in Malay maternal serum. MiRNA expression levels and their unique potential as biomarkers were explored in this work. In GDM patients, the expression levels of hsa-miR-193a, hsa-miR-21, hsa-miR-23a, and hsa-miR-361 were significantly increased, but miR-130a was significantly downregulated. The area under the curve (AUC) and receiver operating characteristic (ROC) curve study demonstrated that hsa-miR-193a (AUC = 0.89060 ± 04,470, P = 0.0001), hsa-miR-21 (AUC = 0.89500 ± 04,411, P = 0.0001), and miR-130a (AUC = 0.6939 ± 0.05845, P = 0.0025) had potential biomarker features in GDM. In-silico analysis also revealed that KLF (Kruppel-Like family of transcription factor), ZNF25 (Zinc finger protein 25), AFF4 (ALF transcription elongation factor 4), C1orf143 (long intergenic non-protein coding RNA 2869), SRSF2 (serine and arginine rich splicing factor 2), and ZNF655 (Zinc finger protein 655) were prominent genes targeted by the common nodes of miR23a, miR130, miR193a, miR21, and miR361.Our findings suggest that circulating microRNAs in the first trimester has the potential for GDM screening in the Malay population.

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“…Excessive maternal inflammatory response accompanied by incomplete remodelling of spiral arterioles have been linked to preterm birth, FGR and pre‐eclampsia 19 . There is also emerging evidence suggesting sexually dimorphic epigenetic regulation of RNA expression in the placenta, 20 as well as influence of fetal sex on maternal vascular adaptation to pregnancy, 1 may influence disparities in obstetric and perinatal outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…1,18 Excessive maternal inflammatory response accompanied by incomplete remodelling of spiral arterioles have been linked to preterm birth, FGR and pre-eclampsia. 19 There is also emerging evidence suggesting sexually dimorphic epigenetic regulation of RNA expression in the placenta, 20 as well as influence of fetal sex on maternal vascular adaptation to pregnancy, 1 may influence disparities in obstetric and perinatal outcomes. Similar to other studies, 9,13,14,21,22 we found male sex was associated with increased odds of neonatal morbidity and mortal-While gestational age is a well-known predictor for perinatal outcomes, 23,24 composite neonatal for male infants from as early as 29 weeks of gestation peaking at 37 to 38 weeks.…”

Section: Discussionmentioning

confidence: 99%

Male infants are at higher risk of neonatal mortality and severe morbidity

Wong

Schreiber

Crawford

et al. 2023

Aust NZ J Obst Gynaeco

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BackgroundWhile a male infant is usually born with a higher birthweight than his female counterpart, he is more at risk of variety of adverse perinatal outcomes. Indeed, throughout life, females exhibit a marked survival advantage compared to males. The aetiology for such pertinent sex disparity remains unclear and is likely multifactorial.AimsThe aim of this study was to investigate obstetric and perinatal outcomes by infant sex from 28 weeks in a contemporary, large Australian birth cohort.Materials and MethodsA 14‐year retrospective cohort study of 130 133 births over 28 weeks gestation from a single tertiary centre.ResultsMale infants had overall higher rates of neonatal mortality (0.12% vs 0.06%, P < 0.001) and severe neonatal morbidity (12% vs 9.1%, P < 0.001) (adjusted odds ratio (aOR) 1.41, 95% CI 1.35–1.47). The odds of overall perinatal mortality (stillbirth and neonatal death) were higher for male infants (aOR 1.30, 95% CI 1.08–1.56). The difference in severe neonatal morbidity when stratified by gestational age at birth only remained significant from >35 weeks gestation. Regardless of infant sex, rates of neonatal mortality and morbidity were lowest at 39 weeks gestation. Rates of preterm birth and operative birth were also higher for male infants.ConclusionsOur study demonstrates significant disparities in clinical outcomes by infant sex with males at a disadvantage to female infants.

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Sex differences in microRNA expression in first and third trimester human placenta

Cited by 10 publications

References 88 publications

Female‐to‐male differential transcription patterns of miRNA‐mRNA networks in the livers of dioxin‐exposed mice

Female‐to‐male differential transcription patterns of miRNA‐mRNA networks in the livers of dioxin‐exposed mice

Analysis of serum circulating MicroRNAs level in Malaysian patients with gestational diabetes mellitus

Male infants are at higher risk of neonatal mortality and severe morbidity

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