Decreased Vitamin D Levels and Altered Placental Vitamin D Gene Expression at High Altitude: Role of Genetic Ancestry
High-altitude hypoxia challenges reproduction; particularly in non-native populations. Although high-altitude residence is associated with vitamin D deficiency, the homeostasis and metabolism of vitamin D in natives and migrants remain unknown. We report that high altitude (3600 m residence) negativ...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/4/3389 |
| Summary: | High-altitude hypoxia challenges reproduction; particularly in non-native populations. Although high-altitude residence is associated with vitamin D deficiency, the homeostasis and metabolism of vitamin D in natives and migrants remain unknown. We report that high altitude (3600 m residence) negatively impacted vitamin D levels, with the high-altitude Andeans having the lowest 25-OH-D levels and the high-altitude Europeans having the lowest 1α,25-(OH)<sub>2</sub>-D levels. There was a significant interaction of genetic ancestry with altitude in the ratio of 1α,25-(OH)<sub>2</sub>-D to 25-OH-D; with the ratio being significantly lower in Europeans compared to Andeans living at high altitude. Placental gene expression accounted for as much as 50% of circulating vitamin D levels, with <i>CYP2R1</i> (25-hydroxylase), <i>CYP27B1</i> (1α-hydroxylase), <i>CYP24A1</i> (24-hydroxylase), and <i>LRP2</i> (megalin) as the major determinants of vitamin D levels. High-altitude residents had a greater correlation between circulating vitamin D levels and placental gene expression than low-altitude residents. Placental 7-dehydrocholesterol reductase and vitamin D receptor were upregulated at high altitude in both genetic-ancestry groups, while megalin and 24-hydroxylase were upregulated only in Europeans. Given that vitamin D deficiency and decreased 1α,25-(OH)<sub>2</sub>-D to 25-OH-D ratios are associated with pregnancy complications, our data support a role for high-altitude-induced vitamin D dysregulation impacting reproductive outcomes, particularly in migrants. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |