Early to mid-gestational testosterone excess leads to adverse lung programming in sheep offspring.

Authors

Md Rahatullah Razan, Kel Vin Woo, Divya Purswani, David Bernal, Bashar Alkhatib, Tiandao Li, Vasantha Padmanabhan, Arpita Kalla Vyas

Published in

American journal of physiology. Lung cellular and molecular physiology. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Prenatal testosterone (T) excess programs sex-specific cardiovascular dysfunction in sheep offspring. Given the close reciprocal relationship between the cardiopulmonary system, we hypothesized that prenatal T excess would also adversely program the offspring's pulmonary system in a sex-specific manner from fetal life into adulthood. Pregnant ewes received intramuscular injections of T propionate (100 mg) or a vehicle control (C) twice weekly from gestational days (GD) 30-90 (term 147 days). Offspring lungs were collected at GD120 (n=6-7 per group), and at 24 months of age (n=4-6 per group) for histological and molecular analyses. Data were analyzed using two-way ANOVA (fetal) and/or sex-specific stratified t-tests for adults and Cohen's effect size analyses. Prenatal T significantly increased fetal lung collagen deposition in males. Prenatal T treatment had a significant overall treatment main effect on fetal lung apoptosis and the ratio of small to total blood vessels. Some adverse effects of prenatal T excess persisted into adulthood, including a significant increase in lung collagen in both sexes. Fetal lung transcriptome revealed differential enrichment of pathways involved in regulation of hormone biosynthetic process, and neuron apoptotic process in T- treated males, whereas pathways related to bicarbonate transport and regulation of muscle cell differentiation were enriched in T- treated females. Overall, early- to mid-gestational T excess adversely reprograms the offspring's lungs in a sex-specific manner, from fetal life extending into adulthood.

PMID:
42832382
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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