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Isolation and Differentiation of Primary White and Brown Preadipocytes from Newborn Mice
Published on: January 25, 2021
Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs
Marc Simard1, Pierre R Provost, Yves Tremblay
1Laboratory of Ontogeny and Reproduction, CHUQ, PCHUL, Faculty of Medicine, Laval University, Québec City, Québec, Canada. marc.simard@crchul.ulaval.ca
Insights
Male fetuses show delayed lung maturation, impacting surfactant production. Gene profiling identified sex-specific genes, including apolipoproteins, potentially involved in this delay and neonatal respiratory distress.
Area of Science:
- Developmental Biology
- Genomics
- Neonatology
Background:
- Neonatal respiratory distress is more common in males, linked to delayed lung maturation and surfactant synthesis.
- Androgen levels are implicated, but specific genes influencing sex-based lung development differences remain unidentified.
- This study investigated sex differences in developing mouse lung gene expression.
Purpose of the Study:
- To identify genes involved in lung maturation that show differential expression between male and female fetal mice.
- To explore the genetic basis for sex differences in lung development and surfactant synthesis.
- To find potential candidate genes contributing to neonatal respiratory distress.
Main Methods:
- Gene expression profiling using oligonucleotide microarrays (Affymetrix MOE430A) on mouse fetal lungs.
- Analysis of RNA from male and female mice at gestational days 15.5, 16.5, and 17.5.
- Statistical analysis using MAS5.0, LFCM, and Genesis software.
Main Results:
- Out of approximately 14,000 transcripts, 83 genes showed sex-based differential expression between gestational days 15.5 and 17.5.
- These included genes in hormone metabolism, apoptosis, signal transduction, transcriptional regulation, and lipid metabolism (four apolipoproteins).
- Immune function and other metabolic genes also exhibited sex-specific expression patterns.
Conclusions:
- Several sexually dimorphic genes identified are potential candidates for roles in lung maturation.
- Pulmonary expression of apolipoprotein genes, involved in lipid transport, correlated with sex differences in surfactant lipids on gestational day 17.5.
- These findings suggest a role for apolipoproteins in surfactant synthesis and may help identify genes in neonatal respiratory distress pathophysiology.
Background:
In human, respiratory distress of the neonates, which occurs in prematurity, is prevalent in male. Late in gestation, maturation of type II pneumonocytes, and consequently the surge of surfactant synthesis are delayed in male fetuses compared with female fetuses. Although the presence of higher levels of androgens in male fetuses is thought to explain this sex difference, the identity of genes involved in lung maturation that are differentially modulated according to fetal sex is unknown. We have studied the sex difference in developing mouse lung by gene profiling during a three-day gestational window preceding and including the emergence of mature PTII cells (the surge of surfactant synthesis in the mouse occurs on GD 17.5).
Methods:
Total RNA was extracted from lungs of male and female fetal mice (gestation days 15.5, 16.5, and 17.5), converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays (Affymetrix MOE430A). Analysis of data was performed using MAS5.0, LFCM and Genesis softwares.
Results:
Many genes involved in lung maturation were expressed with no sex difference. Of the approximative 14,000 transcripts covered by the arrays, only 83 genes presented a sex difference at one or more time points between GDs 15.5 and 17.5. They include genes involved in hormone metabolism and regulation (i.e. steroidogenesis pathways), apoptosis, signal transduction, transcriptional regulation, and lipid metabolism with four apolipoprotein genes. Genes involved in immune functions and other metabolisms also displayed a sex difference.
Conclusion:
Among these sexually dimorphic genes, some may be candidates for a role in lung maturation. Indeed, on GD 17.5, the sex difference in surfactant lipids correlates with the sex difference in pulmonary expression of apolipoprotein genes, which are involved in lipid transport. This suggests a role for these genes in the surge of surfactant synthesis. Our results would help to identify novel genes involved in the physiopathology of the respiratory distress of the neonates.
