A5059913787- Ovarian function and disorders
- Hypothalamic control of reproductive hormones
- Plant Reproductive Biology
- Genomics and Chromatin Dynamics
- Reproductive Biology and Fertility
- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Congenital limb and hand anomalies
- Reproductive System and Pregnancy
- Hedgehog Signaling Pathway Studies
- Genomic variations and chromosomal abnormalities
University of California, San Diego
2015-2024
Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a rat model using letrozole (LET), nonsteroidal aromatase inhibitor, mimicked multiple phenotypes, including metabolic features absent in other models. Given the advantages genetic and transgenic mouse models, we investigated whether LET produces similar phenotype mice. Pubertal female C57BL/6N mice were treated for 5 wk with...
Enhancers control the location and timing of gene expression contain majority variants associated with disease
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology unknown, excess androgens are thought to be a critical factor driving pathology PCOS. We previously demonstrated that continuous exposure aromatase inhibitor letrozole (LET) mice produces many hallmarks PCOS, including elevated testosterone (T) luteinizing hormone, obesity. In current study, we sought...
Abstract Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by elevated androgens and antimüllerian hormone (AMH). These hormones remain throughout pregnancy, potential effects of exposure on offspring from women with PCOS largely unexplored. Expanding recent reports prenatal AMH in mice, we have fully the consequences (pAMH) lifespan first- second-generation both sexes. We also sought to elucidate mechanisms underlying pAMH-induced effects. There known...
Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested androgens may regulate GnRHR, although mechanisms remain unknown. In this study, we demonstrated positively Gnrhr mRNA in mice. We then investigated effects of and androgen (AR) on promoter activity immortalized mouse LβT2 cells, which represent mature gonadotropes. found AR regulates proximal...
Summary An emerging regulatory principle governing enhancers is the use of suboptimal affinity binding sites to encode tissue-specific gene expression. Here we investigate if optimizing single-nucleotide variants that violate this can disrupt expression and development. The ZRS enhancer mediates Shh in posterior developing limb buds critical for digit We find contains suboptimal-affinity ETS sites. Two human mutations a synthetic mutation optimize ETS-A site from 0.15 0.25 relative cause...