Gender and sex hormone effects on neonatal innate immune function

• Published in: The journal of maternal-fetal & neonatal medicine 2024-12, Vol.37 (1), p.2334850-2334850
• Main Authors: McGovern, Matthew, Kelly, Lynne, Finnegan, Rebecca, McGrath, Roisin, Kelleher, John, El-Khuffash, Afif, Murphy, John, Greene, Catherine M, Molloy, Eleanor J
• Format: Article
• Language: English
• Subjects: Case-Control Studies; Female; Genes, X-Linked; Gonadal Steroid Hormones - blood; Humans; Immunity, Innate - genetics; Infant, Newborn; Infant, Premature - immunology; Male; MicroRNAs - genetics; Monocytes - immunology; Monocytes - metabolism; Neutrophils - immunology; Neutrophils - metabolism; Sex Factors
• ISSN: 1476-7058; 1476-4954
• DOI: 10.1080/14767058.2024.2334850

Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations. Preterm infants (  = 21) and term control (  = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes. Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates. This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses