Estrogens Regulate Placental Angiogenesis in Horses.

Area of Science:

• Reproductive Biology
• Developmental Biology
• Comparative Physiology

Background:

• A functional placental vascular network is essential for pregnancy success.
• Abnormal placental vascularization is linked to various pregnancy complications.
• Estrogens are abundant during equine gestation and may regulate placental development.

Purpose of the Study:

• To investigate the role of estrogens in regulating placental vascular network formation in horses (Equus caballus).
• To determine if estrogen suppression affects fetal growth and placental vascular development during the first trimester.

Main Methods:

• Administration of letrozole (aromatase inhibitor) to mares during the first trimester (Days 30-118).
• Measurement of circulating hormone concentrations (estrone sulfate, testosterone, androstenedione).
• Analysis of gene expression (CYP17A1, androgen receptor, ANGPT1, VEGF, NOS2) in the chorioallantois (CA) at Day 120.
• Assessment of fetal weight and CA vascularity.
• In vitro studies using equine endothelial cells treated with 17β-estradiol.

Main Results:

• Letrozole treatment reduced circulating estrone sulfate and tended to reduce fetal weight.
• Gene expression of CYP17A1 increased, while androgen receptor expression decreased in the CA.
• A trend towards decreased vascularity was observed in the CA of letrozole-treated mares.
• Expression of angiogenic genes (ANGPT1, VEGF, NOS2) was altered.
• 17β-estradiol enhanced angiogenic gene expression and endothelial cell activity in vitro.

Conclusions:

• Estrogen suppression during early equine pregnancy impairs placental vascular network development.
• These findings suggest an estrogen-dependent mechanism for vasculogenesis in the equine chorioallantois.
• Estrogens play a significant role in supporting placental vascular formation during the first trimester of equine gestation.