Sex-specific influence of the vacuolar adenosine triphosphatase a2 isoform on outcome in twin pregnancies

Problem: The influence of fetal sex on immune responses in multifetal pregnancies remains incompletely elucidated. The a2 isoform of vacuolar adenosine triphosphatase (a2V) is expressed on the cell membrane of maternal lymphoid cells and contributes to down-regulation of pro-inflammatory immune responses during gestation. The association between fetal sex and a2V expression on peripheral blood mononuclear cells (PBMCs) from mothers with twin gestations was assessed.

Method of study: Patients in this prospective study were 93 women with twin pregnancies in their mid-second or early third trimester-27 with two male, 30 with two female and 36 with one male and one female fetus. PBMCs were isolated and a2V was measured by ELISA in cell lysates. Demographic and clinical data were subsequently obtained and correlations between a2V and fetal sex, birthweight and pregnancy outcome were assessed by the Mann-Whitney and Spearman rank correlation tests.

Results: The mean a2V level was highest when both fetuses were male (2.0 ng/mL) and lowest when both were female (1.5 ng/mL; P = 0.0184). Only when both fetuses were female did the a2V concentration negatively correlate with birthweight of the 1st (P = 0.0011) and 2nd (P = 0.0044) born fetus and with gestational age at delivery (P = 0.0018). There were no associations between a2V and these outcomes in male only or mixed twin pregnancies.

Conclusion: We conclude that the a2V-mediated regulation of maternal immunity during twin pregnancies is influenced by fetal sex.