Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development
| Autor: | Pardis Hosseinzadeh, William Gibbons, Chellakkan S. Blesson, Jamie Merkison, Maya Barsky, Janet Bruno-Gaston, Jay Dunn, L. Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Sex Differentiation medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Ovary Mitochondrion Biology Biochemistry Article Anovulation Fetal Development 03 medical and health sciences 0302 clinical medicine Endocrinology Pregnancy Internal medicine medicine Animals Humans Molecular Biology Fetus Cell Biology Androgen medicine.disease Polycystic ovary 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Dihydrotestosterone Androgens Molecular Medicine Female Folliculogenesis Infertility Female medicine.drug Polycystic Ovary Syndrome |
| Zdroj: | J Steroid Biochem Mol Biol |
| ISSN: | 1879-1220 |
| Popis: | Polycystic ovary syndrome (PCOS) is a common form of anovulatory infertility with a strong hereditary component but no candidate genes have been found. The inheritance pattern may be due to in utero androgen programming on gene expression and mitochondria. Mitochondria are maternally inherited and alterations to mitochondria after fetal androgen exposure may explain one of the mechanisms of fetal programming in PCOS. Our aim was to investigate the role of excessive prenatal androgens in ovarian development by identifying how hyperandrogenemia affects gene expression and mitochondria in neonatal ovary. Pregnant dams were injected with dihydrotestosterone on days 16-18 of pregnancy. Day 0 ovaries were collected for gene expression and mitochondrial studies. RNAseq showed differential gene expressions which were related to mitochondrial dysfunction, fetal gonadal development, oocyte maturation, metabolism, angiogenesis, and PCOS. Top 20 up and downregulated genes were validated with qPCR and Western Blot. Transcriptional pathways involved in folliculogenesis and genes involved in ovarian and mitochondrial function were dysregulated. Further, DHT exposure altered mitochondrial ultrastructure and function by increasing mitochondrial oxygen consumption and decreasing mitochondrial efficiency with increased proton leak within the first day of life. Our data indicates that one path that leads to PCOS begins at birth and is programmed in utero by androgens. |
| Databáze: | OpenAIRE |
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