Maternal estradiol impacts fetal HPA axis and pulmonary transcriptomes in sheep

Area of Science:

• Reproductive Endocrinology
• Fetal Physiology
• Genomics

Background:

• Precise timing of birth and fetal organ maturation is vital for neonatal survival.
• The fetal hypothalamic-pituitary-adrenal (HPA) axis and estradiol (E2) are key regulators of parturition and maturation, but upstream signals are unclear.

Purpose of the Study:

• To investigate if maternal estradiol administration affects fetal endocrine and pulmonary maturation via transcriptional regulation.
• To elucidate the role of maternal estradiol in initiating fetal readiness for birth.

Main Methods:

• Pregnant ewes received maternal estradiol implants or controls.
• Fetal tissues (hypothalamus, pituitary, adrenal, lung) were collected for RNA sequencing and immunohistochemistry.
• Hormone levels in maternal, fetal, and umbilical plasma were analyzed.

Main Results:

• Maternal estradiol increased significantly, while fetal/umbilical levels remained unchanged.
• Transcriptomic analysis revealed significant gene expression changes in the fetal pituitary, lung, adrenal, and hypothalamus.
• Pituitary gene expression changes involved POMC downregulation and pathways related to neurogenesis and cell adhesion. Lung tissue showed increased ERα-positive nuclei.

Conclusions:

• Maternal estradiol induces tissue-specific fetal transcriptomic changes, suggesting a role in endocrine and pulmonary maturation.
• These effects occur independently of changes in fetal circulating estradiol, potentially influencing fetal readiness for birth.
• Maternal estradiol may act indirectly, possibly in conjunction with fetal cortisol, to prepare the fetus for parturition.