Association between fetal sex and maternal plasma microRNA responses to prenatal alcohol exposure: evidence from a birth outcome-stratified cohort

Autor: Rajesh C. Miranda, Lyubov Yevtushok, Wladimir Wertlecki, Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Natalya Zymak-Zakutnya, Christina D. Chambers, Alexander M. Tseng, Amanda H. Mahnke, Nihal A. Salem, Alan Wells
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Physiology
lcsh:Medicine
Reproductive health and childbirth
lcsh:Physiology
Cohort Studies
Alcohol Use and Health
Substance Misuse
0302 clinical medicine
Endocrinology
Pregnancy
Fetal sex
Blood plasma
Infant Mortality
Maternal miRNA co-secretion
Collaborative Initiative on Fetal Alcohol Spectrum Disorders
Fetal alcohol spectrum disorders
Psychomotor learning
Pediatric
lcsh:QP1-981
Alcoholism
Cohort
Female
Human
Biotechnology
Adult
Intellectual and Developmental Disabilities (IDD)
Chromosomes
Gender Studies
03 medical and health sciences
Young Adult
Clinical Research
Sex as a biological variable
microRNA
medicine
Genetics
Humans
Conditions Affecting the Embryonic and Fetal Periods
Association (psychology)
Fetal Alcohol Spectrum Disorders (FASD)
Chromosomes
Human
X
Fetus
Chromosomes
Human
Y
Extracellular miRNAs
Ethanol
business.industry
Research
lcsh:R
Perinatal Period - Conditions Originating in Perinatal Period
medicine.disease
Brain Disorders
MicroRNAs
030104 developmental biology
Good Health and Well Being
Bootstrap resampling
business
030217 neurology & neurosurgery
Zdroj: Biology of sex differences, vol 11, iss 1
Biology of Sex Differences, Vol 11, Iss 1, Pp 1-17 (2020)
Biology of Sex Differences
Popis: Most persons with fetal alcohol spectrum disorders (FASDs) remain undiagnosed or are diagnosed in later life. To address the need for earlier diagnosis, we previously assessed miRNAs in the blood plasma of pregnant women who were classified as unexposed to alcohol (UE), heavily exposed with affected infants (HEa), or heavily exposed with apparently unaffected infants (HEua). We reported that maternal miRNAs predicted FASD-related growth and psychomotor deficits in infants. Here, we assessed whether fetal sex influenced alterations in maternal circulating miRNAs following prenatal alcohol exposure (PAE). To overcome the loss of statistical power due to disaggregating maternal samples by fetal sex, we adapted a strategy of iterative bootstrap resampling with replacement to assess the stability of statistical parameter estimates. Bootstrap estimates of parametric and effect size tests identified male and female fetal sex-associated maternal miRNA responses to PAE that were not observed in the aggregated sample. Additionally, we observed, in HEa mothers of female, but not male fetuses, a network of co-secreted miRNAs whose expression was linked to miRNAs encoded on the X-chromosome. Interestingly, the number of significant miRNA correlations for the HEua group mothers with female fetuses was intermediate between HEa and UE mothers at mid-pregnancy, but more similar to UE mothers by the end of pregnancy. Collectively, these data show that fetal sex predicts maternal circulating miRNA adaptations, a critical consideration when adopting maternal miRNAs as diagnostic biomarkers. Moreover, a maternal co-secretion network, predominantly in pregnancies with female fetuses, emerged as an index of risk for adverse birth outcomes due to PAE.
Databáze: OpenAIRE
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