Developmental programming: exposure to testosterone excess disrupts steroidal and metabolic environment in pregnant sheep

Endocrinology
B Abi SalloumVasantha Padmanabhan

Abstract

Gestational exposure to excess T leads to intrauterine growth restriction, low birth weight, and adult metabolic/reproductive disorders in female sheep. We hypothesized that as early mediators of such disruptions, gestational T disrupts steroidal and metabolic homeostasis in both the mother and fetus by both androgenic and metabolic pathways. Maternal blood samples were measured weekly for levels of insulin, glucose, and progesterone from four groups of animals: control; gestational T (twice weekly im injections of 100 mg of T propionate from d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg·d oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11 mg/kg·d oral; T-Rosi) (n = 10-12/group). On day 90 of gestation, maternal and umbilical cord samples were collected after a 48-hour fast from a subset (n = 6/group) for the measurement of steroids, free fatty acids, amino acids, and acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P < .05), which was prevented by flutamide showing direct androgenic mediation. Gestational T also augmented maternal insulin levels and decreased medium chained acylcarnitines, suggesting increased mitochondrial fatty acid oxidat...Continue Reading

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Citations

Dec 8, 2015·Molecular and Cellular Endocrinology·Muraly PuttabyatappaVasantha Padmanabhan
Aug 31, 2017·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Monica RecabarrenSergio E Recabarren
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Apr 21, 2020·Endocrine Reviews·Elisabet Stener-VictorinDavid H Abbott
Feb 10, 2016·Endocrinology·Vasantha PadmanabhanMuraly Puttabyatappa
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Jul 25, 2019·Medical Sciences : Open Access Journal·Rodolfo C Cardoso, Vasantha Padmanabhan
Nov 8, 2020·Reproductive Biology and Endocrinology : RB&E·Renata S M LandersRodolfo C Cardoso
Jul 30, 2020·Molecular and Cellular Endocrinology·Ian J JacksonVasantha Padmanabhan

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