ArticleJournal of translational medicine2021
Effect of the spatial-temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse.
Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Anti-androgen therapy in polyendocrine metabolic ovary syndrome (PMOS, formerly PCOS): efficacy, safety, and phenotype-oriented clinical decision-making.Journal of ovarian research · 2026Review
- Knockout ofZoological research · 2026Article
- Ovarian-Specific Cyp17A1 Overexpression in Female Mice: A Novel Model of Endogenous Testosterone Excess.Endocrinology · 2025Article
- Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.Human reproduction update · 2024Review
- The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.Current osteoporosis reports · 2023Review
- Update on Animal Models of Polycystic Ovary Syndrome.Endocrinology · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIn the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown.
methodsIn this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system.
resultsOvaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis).
conclusionsOur novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.
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