(928) Sexual Dimorphism in Chorion Trophoblastic Cells

Objective: Differences in clinical premature birth outcomes and intrauterine tissue inflammation have been observed between male (M) and female (F) neonates. These observations have been identified in placental trophoblast tissue, but sexual-level differences are unknown to occur within the fetal membrane trophoblast layer (chorion trophoblasts [CTC]). This study examined whether there is evidence for sex-based differences in gene expression and inflammatory marker expression in CTCs, and their differential response due to infectious stimuli, modeling infection-associated preterm birth.

Study Design: CTC from six different patient-derived fetal membrane samples (three M and three F) (Fig. 1A) were cultured and divided into experimental and control groups. Lipopolysaccharide (LPS) was a proxy for infection, and CTC were stimulated for 6, 12, or 24H (hours). RNA from Cells were subjected to RNA-seq. Multiplex cytokine kits or ELISA detected secreted pro- and anti-inflammatory cytokines (IL-6, IL-8, TNFα, GM-CSF; IL-10), progesterone (P4), and soluble HLA-G in cell supernatants to determine inflammatory status and endocrine responses.

Results: CTC-M & CTC-F showed sex, time, and stimulant-dependent differential gene expression profiles (Fig. 1B). Cytokine analysis demonstrated a significantly lower IL-6 production in control CTC-M than in CTC-F (Fig. 1C). No sex-dependent responses were observed in CTCs after LPS treatment regarding pro- or anti-inflammatory cytokines. CTC-M produced significantly lower P4 than CTC-F (Fig. 1D).

Conclusion: The theories of sexual dimorphism linked to placental inflammation do not extend to fetal membrane trophoblasts. This study supports current evidence that the chorion acts as a “great wall” which protects the fetus from external infection by being refractory to insults. Further examination into the weaknesses of the chorion barrier and redirection of study efforts that examine sex-dependent responses of fetal membranes is needed.