Androgen receptor-dependent myometrial remodeling links hyperandrogenism to prolonged second-stage labor in PCOS
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE346426 | GEO | 2026/09/10
REPOSITORIES: GEO
Similar Datasets
Project description:Maternal hyperandrogenism is closely related to metabolic disorders, yet its transgenerational effects on male descendants remain unclear. Here we demonstrate that hyperandrogenism in women predisposes their sons to islet β-cell dysfunction. Male offspring mice with prenatal androgen exposure exhibited hyperglycemia and glucose intolerance due to compromised insulin secretion. Notably, these metabolic disturbances were transmitted across three generations, and exacerbated by aging and a high-fat diet. Altered DNA methylations in F1 sperm and F2 islet contribute to suppressed β-cell functional genes. We identified shared differentially methylated signatures in F1 sperm, type 2 diabetes patients, and sons with maternal hyperandrogenism. Furthermore, caloric restriction and metformin treatments in F1 males corrected hyperglycemic defects and prevented their transmission to offspring. Our findings highlight the transgenerational inheritance of hyperglycemia and β-cell dysfunction in male offspring from maternal hyperandrogenism via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.
2025-02-19 | GSE266699 | GEO
Project description:Maternal hyperandrogenism is closely related to metabolic disorders, yet its transgenerational effects on male descendants remain unclear. Here we demonstrate that hyperandrogenism in women predisposes their sons to islet β-cell dysfunction. Male offspring mice with prenatal androgen exposure exhibited hyperglycemia and glucose intolerance due to compromised insulin secretion. Notably, these metabolic disturbances were transmitted across three generations, and exacerbated by aging and a high-fat diet. Altered DNA methylations in F1 sperm and F2 islet contribute to suppressed β-cell functional genes. We identified shared differentially methylated signatures in F1 sperm, type 2 diabetes patients, and sons with maternal hyperandrogenism. Furthermore, caloric restriction and metformin treatments in F1 males corrected hyperglycemic defects and prevented their transmission to offspring. Our findings highlight the transgenerational inheritance of hyperglycemia and β-cell dysfunction in male offspring from maternal hyperandrogenism via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.
2025-02-19 | GSE266255 | GEO
Project description:Androgen receptor-dependent myometrial remodeling links hyperandrogenism to prolonged second-stage labor in PCOS
| PRJNA1525542 | ENA
Project description:Wildfires have become more frequent and intense worldwide. Wildfire smoke particulate matter (WFPM) can be more toxic than urban background PM due to nanosized PM or WFPM0.1 and more polar organic compounds including polycyclic aromatic hydrocarbons (PAHs). While WFPM has been linked to cardiopulmonary diseases, its impact on female reproduction remains elusive. Here, we used an in vivo mouse intratracheal exposure model and a 3D ovarian follicle culture system, together with molecular, transcriptomics, and computational analyses, to examine the effects of lab-synthesized (LS) and Canadian real-world WFPM0.1 (C- WFPM0.1) on ovarian functions. Intratracheal exposure to LS-WFPM0.1 disrupted estrous cycles and elevated serum estradiol and testosterone concentrations in young adult female mice. RT-qPCR and single-follicle RNA-sequencing (RNA-seq) analysis analysis revealed altered steroidogenic genes, transcriptomic changes, and activation of aryl hydrocarbon receptor (AhR) in antral follicles of from LS-WFPM0.1-treated mice. In vitro exposure revealed thatto LS-WFPM0.1 increased testosterone secretion and induced genes related to androgen synthesis and AhR. Single-follicle and single-oocyte RNA-seq analysis identified differentially expressed genes (DEGs) related to inflammation in somatic cells and mitochondria and cell cycle in oocytes. Both real-world C-WFPM0.1 from the 2023 Canadian wildfires and benzo[a]pyrene, a high molecule weight PAH, reproduced these ovarian defects caused by LS-WFPM0.1. Mechanistically, AhR inhibition reversed hyperandrogenism induced by WFPM0.1. Together, our findings demonstrate that PAH-containing WFPM0.1 perturbs ovarian steroidogenesis and induces hyperandrogenism through AhR activation. These results are crucial for developing strategies to protect women’s reproductive health and tailor guidelines for women seeking for infertility treatment during wildfire seasons.
2026-02-16 | GSE317185 | GEO
Project description:Wildfires have become more frequent and intense worldwide. Wildfire smoke particulate matter (WFPM) can be more toxic than urban background PM due to nanosized PM or WFPM0.1 and more polar organic compounds including polycyclic aromatic hydrocarbons (PAHs). While WFPM has been linked to cardiopulmonary diseases, its impact on female reproduction remains elusive. Here, we used an in vivo mouse intratracheal exposure model and a 3D ovarian follicle culture system, together with molecular, transcriptomics, and computational analyses, to examine the effects of lab-synthesized (LS) and Canadian real-world WFPM0.1 (C- WFPM0.1) on ovarian functions. Intratracheal exposure to LS-WFPM0.1 disrupted estrous cycles and elevated serum estradiol and testosterone concentrations in young adult female mice. RT-qPCR and single-follicle RNA-sequencing (RNA-seq) analysis analysis revealed altered steroidogenic genes, transcriptomic changes, and activation of aryl hydrocarbon receptor (AhR) in antral follicles of from LS-WFPM0.1-treated mice. In vitro exposure revealed thatto LS-WFPM0.1 increased testosterone secretion and induced genes related to androgen synthesis and AhR. Single-follicle and single-oocyte RNA-seq analysis identified differentially expressed genes (DEGs) related to inflammation in somatic cells and mitochondria and cell cycle in oocytes. Both real-world C-WFPM0.1 from the 2023 Canadian wildfires and benzo[a]pyrene, a high molecule weight PAH, reproduced these ovarian defects caused by LS-WFPM0.1. Mechanistically, AhR inhibition reversed hyperandrogenism induced by WFPM0.1. Together, our findings demonstrate that PAH-containing WFPM0.1 perturbs ovarian steroidogenesis and induces hyperandrogenism through AhR activation. These results are crucial for developing strategies to protect women’s reproductive health and tailor guidelines for women seeking for infertility treatment during wildfire seasons.
2026-02-16 | GSE317095 | GEO
Project description:Wildfires have become more frequent and intense worldwide. Wildfire smoke particulate matter (WFPM) can be more toxic than urban background PM due to nanosized PM or WFPM0.1 and more polar organic compounds including polycyclic aromatic hydrocarbons (PAHs). While WFPM has been linked to cardiopulmonary diseases, its impact on female reproduction remains elusive. Here, we used an in vivo mouse intratracheal exposure model and a 3D ovarian follicle culture system, together with molecular, transcriptomics, and computational analyses, to examine the effects of lab-synthesized (LS) and Canadian real-world WFPM0.1 (C- WFPM0.1) on ovarian functions. Intratracheal exposure to LS-WFPM0.1 disrupted estrous cycles and elevated serum estradiol and testosterone concentrations in young adult female mice. RT-qPCR and single-follicle RNA-sequencing (RNA-seq) analysis analysis revealed altered steroidogenic genes, transcriptomic changes, and activation of aryl hydrocarbon receptor (AhR) in antral follicles of from LS-WFPM0.1-treated mice. In vitro exposure revealed thatto LS-WFPM0.1 increased testosterone secretion and induced genes related to androgen synthesis and AhR. Single-follicle and single-oocyte RNA-seq analysis identified differentially expressed genes (DEGs) related to inflammation in somatic cells and mitochondria and cell cycle in oocytes. Both real-world C-WFPM0.1 from the 2023 Canadian wildfires and benzo[a]pyrene, a high molecule weight PAH, reproduced these ovarian defects caused by LS-WFPM0.1. Mechanistically, AhR inhibition reversed hyperandrogenism induced by WFPM0.1. Together, our findings demonstrate that PAH-containing WFPM0.1 perturbs ovarian steroidogenesis and induces hyperandrogenism through AhR activation. These results are crucial for developing strategies to protect women’s reproductive health and tailor guidelines for women seeking for infertility treatment during wildfire seasons.
2026-02-16 | GSE317094 | GEO
Project description:Wildfires have become more frequent and intense worldwide. Wildfire smoke particulate matter (WFPM) can be more toxic than urban background PM due to nanosized PM or WFPM0.1 and more polar organic compounds including polycyclic aromatic hydrocarbons (PAHs). While WFPM has been linked to cardiopulmonary diseases, its impact on female reproduction remains elusive. Here, we used an in vivo mouse intratracheal exposure model and a 3D ovarian follicle culture system, together with molecular, transcriptomics, and computational analyses, to examine the effects of lab-synthesized (LS) and Canadian real-world WFPM0.1 (C- WFPM0.1) on ovarian functions. Intratracheal exposure to LS-WFPM0.1 disrupted estrous cycles and elevated serum estradiol and testosterone concentrations in young adult female mice. RT-qPCR and single-follicle RNA-sequencing (RNA-seq) analysis analysis revealed altered steroidogenic genes, transcriptomic changes, and activation of aryl hydrocarbon receptor (AhR) in antral follicles of from LS-WFPM0.1-treated mice. In vitro exposure revealed thatto LS-WFPM0.1 increased testosterone secretion and induced genes related to androgen synthesis and AhR. Single-follicle and single-oocyte RNA-seq analysis identified differentially expressed genes (DEGs) related to inflammation in somatic cells and mitochondria and cell cycle in oocytes. Both real-world C-WFPM0.1 from the 2023 Canadian wildfires and benzo[a]pyrene, a high molecule weight PAH, reproduced these ovarian defects caused by LS-WFPM0.1. Mechanistically, AhR inhibition reversed hyperandrogenism induced by WFPM0.1. Together, our findings demonstrate that PAH-containing WFPM0.1 perturbs ovarian steroidogenesis and induces hyperandrogenism through AhR activation. These results are crucial for developing strategies to protect women’s reproductive health and tailor guidelines for women seeking for infertility treatment during wildfire seasons.
2026-02-16 | GSE317100 | GEO
Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in calcium-phosphate medium (CaP) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of calcium-phosphate calcified human cronary aortic smooth muscle cells on day 3.
2022-09-18 | GSE211720 | GEO
Project description:The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II. The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by Angiotensin-II (Ang-II) in vascular smooth muscle cells (VSMC), but its impact on hypertension remains unknown. In our transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), the blood pressure response to chronic Ang-II infusion was significantly reduced as compared to littermate controls. Surprisingly, examination of blood pressure and heart rate under ganglionic blockade revealed a key role for VSMC CaMKII in efferent sympathetic outflow in response to Ang II hypertension. Consistently, the efferent splanchnic nerve activity and plasma phenylephrine concentrations were significantly lower in TG SM-CaMKIIN mice as compared to littermates. Moreover, the aortic depressor nerve activity was reset in hypertensive wild type animals, but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor wall activity may be responsible for the blood pressure difference in Ang-II hypertension. The pulse wave velocity, a measure of vascular wall stiffness in vivo, was increased in aortas of hypertensive compared to normotensive WT animals. However, Ang-II infusion did not alter the pulse wave velocity in transgenic mice, suggesting that CaMKII in VSMC controls structural smooth muscle genes. Accordingly, analysis of gene expression changes in aortas from wild type and TG SM-CaMKIIN hypertensive mice demonstrated that CaMKII inhibition mainly altered the expression of muscle contractile proteins. In contrast, TG SM-CaMKIIN aortas were protected from the Ang-II induced upregulation of genes linked to proliferation, suggesting that CaMKII inhibition prevents the Ang-II-induced reprogramming of smooth muscle cell gene expression towards a proliferative phenotype. 5 WT C57Bl/6 and 5 mice that express the Ca2+/calmodulin-dependent kinase II peptide inhibitor CaMKIIN in smooth muscle only (TG SM-CaMKIIN) were infused with 1.25 ug/kg/min Angiotensin-II by osmotic minipump for 14 days. 5 WT and 5 transgenic mice infused with normal saline served as controls. The mice were sacrificed on day 14 and the thoracic aortas isolated. RNA was isolated and pooled for the following groups: WT (wild type), C (TG SM-CaMKIIN), WT-A (WT with Angiotensin-II), C-A (TG SM-CaMKIIN + Angiotensin-II)
2015-07-01 | E-GEOD-64613 | biostudies-arrayexpress
Project description:The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II. The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by Angiotensin-II (Ang-II) in vascular smooth muscle cells (VSMC), but its impact on hypertension remains unknown. In our transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), the blood pressure response to chronic Ang-II infusion was significantly reduced as compared to littermate controls. Surprisingly, examination of blood pressure and heart rate under ganglionic blockade revealed a key role for VSMC CaMKII in efferent sympathetic outflow in response to Ang II hypertension. Consistently, the efferent splanchnic nerve activity and plasma phenylephrine concentrations were significantly lower in TG SM-CaMKIIN mice as compared to littermates. Moreover, the aortic depressor nerve activity was reset in hypertensive wild type animals, but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor wall activity may be responsible for the blood pressure difference in Ang-II hypertension. The pulse wave velocity, a measure of vascular wall stiffness in vivo, was increased in aortas of hypertensive compared to normotensive WT animals. However, Ang-II infusion did not alter the pulse wave velocity in transgenic mice, suggesting that CaMKII in VSMC controls structural smooth muscle genes. Accordingly, analysis of gene expression changes in aortas from wild type and TG SM-CaMKIIN hypertensive mice demonstrated that CaMKII inhibition mainly altered the expression of muscle contractile proteins. In contrast, TG SM-CaMKIIN aortas were protected from the Ang-II induced upregulation of genes linked to proliferation, suggesting that CaMKII inhibition prevents the Ang-II-induced reprogramming of smooth muscle cell gene expression towards a proliferative phenotype.
2015-07-01 | GSE64613 | GEO