Fetal sex specific differences in human placentation: a prospective cohort study

Area of Science:

• Reproductive biology
• Developmental biology
• Perinatal medicine

Background:

• First trimester placental biomarkers are crucial for assessing pregnancy health.
• Fetal sex may influence placental development and function.
• Environmental factors can interact with fetal sex to affect pregnancy outcomes.

Purpose of the Study:

• To investigate fetal sex-specific differences in first-trimester placental biomarkers.
• To examine the interaction between fetal sex and environmental influences on these biomarkers.
• To compare these differences in physiological versus pathological pregnancies.

Main Methods:

• Prospective cohort study (Generation R Study) including live singleton births.
• Linear regression to assess the effect of fetal sex on placental biomarkers.
• Analysis of first-trimester soluble fms-like tyrosine kinase (s-Flt1), placental growth factor (PLGF), plasminogen activator inhibitor (PAI-2), and homocysteine levels.
• Interaction analyses were performed for fetal sex and environmental influences.

Main Results:

• Significant fetal sex-specific differences were found in s-Flt1, PAI-2, and PLGF levels, with higher concentrations in female placentas.
• No fetal sex-specific differences were observed in pregnancies complicated by pre-eclampsia, preterm birth, or small for gestational age.
• Hyperhomocysteinemia was associated with decreased s-Flt1, PLGF, and PAI-2 in male placentas, but not female placentas.

Conclusions:

• Fetal sex impacts early placentation, but this effect is less apparent in pregnancies with major complications.
• Alternative mechanisms may underlie complications like pre-eclampsia, preterm birth, and SGA, potentially masking fetal sex effects.
• Evidence suggests fetal sex-dependent placental gene-environment interactions exist, particularly concerning homocysteine levels.