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Androgenic potential of human fetal adrenals at the end of the first trimester.

ABSTRACT: The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9-12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9-12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9-12 HFA produced steroids of the ?⁵, ?⁴ and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17?-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3?HSD2 at GW11-12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9-12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.

SUBMITTER: Savchuk I

PROVIDER: S-EPMC5516548 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Androgenic potential of human fetal adrenals at the end of the first trimester.

Savchuk I I Morvan M L ML Antignac J P JP Gemzell-Danielsson K K Le Bizec B B Söder O O Svechnikov K K

Endocrine connections 20170607 6

The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9-12 with focus on their androgenic ...[more]

PMID: 28592511

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Project description:OBJECTIVE:To assess the relationship between first-trimester vaginal bleeding and fetal growth patterns. METHODS:We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, a prospective cohort study of low-risk, nonobese women with healthy lifestyles. Duration of bleeding was self-reported at enrollment (10 0/7 to 13 6/7 weeks of gestation) and categorized as 0, 1, or more than 1 day. Longitudinal measures of fetal biometrics were obtained in up to six study visits, and estimated fetal weight was computed. Growth trajectories were created for biometrics and estimated fetal weight. When global tests among groups was significant (P<.05), week-specific global and pairwise differences were tested. Birth weight and risk of a small-for-gestational-age (SGA) neonate were secondary outcomes. All analyses were adjusted for maternal age, weight, height, parity, and racial-ethnic group and neonatal sex in a sensitivity analysis. RESULTS:In 2,307 eligible women, 410 (17.8%) reported first-trimester bleeding, of whom 176 bled for 1 day and 234 bled for more than 1 day. Women with more than 1 day of bleeding demonstrated decreased fetal abdominal circumference from 34 to 39 weeks of gestation compared with women without bleeding. For women with more than 1 day of bleeding, compared with women without bleeding, estimated fetal weight was 68-107 g smaller from 35 to 39 weeks of gestation. Mean birth weight at term was 88 g smaller, confirming differences in calculated fetal weight, and SGA neonates were delivered to 148 (8.5%), 9 (5.7%), and 33 (15.7%) women in the no bleeding, 1 day, and more than 1 day of bleeding groups, respectively. CONCLUSION:More than 1 day of first-trimester vaginal bleeding was associated with smaller estimated fetal weight late in pregnancy driven by smaller abdominal circumference. The magnitude of decrease in birth weight was small, albeit comparable with observed decreases associated with maternal smoking. It remains unknown whether early pregnancy bleeding is associated with short-term or long-term morbidity and whether additional intervention would be of benefit. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT00912132.

Dataset Information

Androgenic potential of human fetal adrenals at the end of the first trimester.

Publications

Androgenic potential of human fetal adrenals at the end of the first trimester.

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