Sex-dependent differential transcript expression in the placenta of
growth restricted infants
Abstract
Objective: To characterise placental gene expression at term to evaluate
sex-specific genetic changes that occur in small for gestational age
(SGA) infants. Design: Case control study. Setting: Australian
hospitals. Samples: Twelve human placental samples from pregnancies that
were either SGA or appropriate for gestational age (AGA). Methods:
RNA-sequencing of term placental tissue from both SGA and AGA infants.
Candidate genes associated with fetal size and fetal sex were identified
using differential gene expression and weighted gene co-expression
network analyses. Single-cell sequencing data was used for candidate
validation and to estimate candidate transcript expression in specific
placental cell populations. Main outcome measures: Functions of
differentially expressed genes in the placenta of SGA infants that
differed by fetal sex. Results: Differential gene expression and
weighted gene co-expression network analyses identified 403 candidate
transcripts associated with SGA infants. One hundred and three of these
transcripts showed sex-specific expression. Sex-independent transcript
expression for genes involved in protein synthesis, and sex-dependent
transcript expression for genes involved in cell cycle processes in
males and endoplasmic reticulum stress in females was validated (17 and
7 transcripts for females and males) in published placental
RNA-sequencing datasets. Conclusions: Sexual dimorphism is an important
consideration when examining placental dysfunction and poor fetal
growth. This study identified activation of shared and divergent
molecular mechanisms (i.e., cell cycle and endoplasmic reticulum
stress), in response to an adverse environmental stressor.