Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion.
|Number of pages
|Published - 2017
Bibliographical noteFunding Information:
The authors acknowledge the generous support of the John P Hughes and Albert G Clay Endowments that funded these studies. The authors are extremely grateful for the technical staff at the Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, especially the support of Dr Heather Knych, Daniel McKemie, Teresa Bowers, Go Sugiarto and Sandy Yim, who provided expertise, training, technical support and guidance for analysis of samples by liquid chromatography tandem mass spectroscopy. The authors also wish to thank Dr Alex Esteller-Vico, Dr Claudia Fernandes, Dr Yatta Boakari, Dr Pouya Dini, Michelle Wynn, and Blaire Fleming for their assistance with tissue collection. Finally, we must acknowledge the insightful, constructive and extremely helpful comments from the anonymous reviewers who critiqued this manuscript.
© 2017 Society for Reproduction and Fertility.
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology
- Cell Biology