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Developmental Programming: Does Prenatal Steroid Excess Disrupt the Ovarian VEGF System in Sheep?
Hugo Héctor Ortega1, Almudena Veiga-Lopez2, Shilpa Sreedharan2
1Department of Morphological Sciences, Faculty of Veterinary Sciences, National University of Litoral, Esperanza, Santa Fe, Argentina Argentine National Research Council (CONICET), Esperanza, Santa Fe, Argentina.
Biology of Reproduction
|July 17, 2015
Summary
Prenatal excess testosterone disrupts ovarian cycles in sheep. While vascular endothelial growth factor (VEGF) system expression remained unchanged, prenatal androgens altered ovarian artery development, potentially contributing to altered follicular growth.
Area of Science:
- Reproductive Endocrinology
- Developmental Programming
- Ovarian Physiology
Background:
- Prenatal exposure to androgens, like testosterone (T), is known to disrupt female reproductive cycles.
- The vascular endothelial growth factor (VEGF) system plays a role in follicular development and vascularization.
- The impact of prenatal T and dihydrotestosterone (DHT) on the VEGF system and ovarian vasculature is not fully understood.
Purpose of the Study:
- To investigate the effects of prenatal T and DHT excess on the expression of VEGFA, VEGFB, and their receptors (VEGFR-1, VEGFR-2, VEGFR-3) in the sheep ovary.
- To examine the impact of prenatal androgen exposure on ovarian arterial morphometry.
Main Methods:
- Sheep were treated with T or DHT from Days 30 to 90 of gestation.
- Immunohistochemistry was used to assess protein expression of VEGF family members and receptors in ovarian tissues at various fetal and postnatal ages.
- Arterial morphometry of ovarian hilar arteries was performed at Fetal Day 140 and postpuberty.
Main Results:
- Prenatal T/DHT treatments did not alter the expression of VEGFA, VEGFB, or their receptors (VEGFR-1, VEGFR-2, VEGFR-3) in the sheep ovary across different developmental stages.
- VEGFA and VEGFB were expressed in granulosa and theca cells, with increased expression in antral follicles.
- Prenatal T and DHT exposure led to larger ovarian hilar arteries (area, wall thickness, wall area) by Fetal Day 140, indicating early programming of vascular development.
Conclusions:
- The disruption of ovarian cyclicity by prenatal testosterone excess in sheep is not mediated by alterations in the ovarian VEGF system's expression.
- Prenatal androgen exposure programs ovarian arterial development, potentially influencing blood flow and endocrine factor delivery.
- This altered vascularization may indirectly contribute to the multifollicular ovarian phenotype observed in androgenized females.
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