Abstract
Dexamethasone (DEX) initiates parturition by inducing progesterone withdrawal and affecting placental steroidogenesis, but the effects of DEX in fetal and maternal tissue steroid synthetic capacity remains poorly investigated. Blood was collected from cows at 270 days of gestation before DEX or saline (SAL) treatment, and blood and tissues were collected at slaughter 38 h later. Steroid concentrations were determined by liquid chromatography tandem mass spectrometry to detect multiple steroids including 5α-reduced pregnane metabolites of progesterone. The activities of 3β-hydroxysteroid dehydrogenase (3βHSD) in cotyledonary and luteal microsomes and mitochondria and cotyledonary microsomal 5α-reductase were assessed. Quantitative PCR was used to further assess transcripts encoding enzymes and factors supporting steroidogenesis in cotyledonary and luteal tissues. Serum progesterone, pregnenolone, 5α-dihydroprogesterone (DHP) and allopregnanolone (3αDHP) concentrations (all <5 ng/mL before treatment) decreased in cows after DEX. However, the 20α-hydroxylated metabolite of DHP, 20αDHP, was higher before treatment (≈100 ng/ mL) than at slaughter but not affected by DEX. Serum, cotyledonary and luteal progesterone was lower in DEX- than SAL-treated cows. Progesterone was >100-fold higher in luteal than cotyledonary tissues, and serum and luteal concentrations were highly correlated in DEX-treated cows. 3βHSD activity was >5-fold higher in luteal than cotyledonary tissue, microsomes had more 3βHSD than mitochondria in luteal tissue but equal in cotyledonary sub-cellular fractions. DEX did not affect either luteal or cotyledonary 3βHSD activity but luteal steroidogenic enzyme transcripts were lower in DEX-treated cows. DEX induced functional luteal regression and progesterone withdrawal before any changes in placental pregnene/pregnane synthesis and/or metabolism were detectable.
| Original language | English |
|---|---|
| Pages (from-to) | 413-422 |
| Number of pages | 10 |
| Journal | Reproduction |
| Volume | 157 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2019 |
Bibliographical note
Publisher Copyright:© 2019 Society for Reproduction and Fertility
Funding
The authors thank the Central Grasslands Research Extension Center, the Animal Nutrition and Physiology Center, and the Physiology Laboratory of the Department of Animal Sciences, NDSU, for their assistance with the animal husbandry, tissue collections and laboratory analyses; especially important were Bryan Neville, Mellissa Crosswhite, Sarah Underdahl, Nicolas Negrin, Matthew Crouse and Amelia Tanner. They also thank Lauren Hulsman Hanna for assistance with statistical analyses. They acknowledge the financial support of an Academic Scholarship, ‘Steroids in regulation of parturition, fetal maturation, and placental expulsion,’ from the Society for Reproduction and Fertility, UK, to L P R and A J C. Financial support of the North Dakota Agricultural Experiment Station is also acknowledged. The authors are equally grateful for the technical assistance of the staff at the Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, especially the efforts and support of Daniel McKemie, Teresa Bowers, Dr. Go Sugiarto and Sandy Yim, providing expertise, training and support for analysis of samples by liquid chromatography tandem mass spectrometry. The authors gratefully acknowledge the Academic Scholarship, ‘Steroids in regulation of parturition, fetal maturation, and placental expulsion,’ from the Society for Reproduction and Fertility (to L P R and A J C) and support from the North Dakota Agricultural Experiment Station.
| Funders | Funder number |
|---|---|
| Society for Reproduction and Fertility, UK | |
| North Dakota Agricultural Experiment Station | |
| Society for Reproduction and Fertility |
ASJC Scopus subject areas
- Reproductive Medicine
- Embryology
- Endocrinology
- Obstetrics and Gynecology
- Cell Biology