A5054418704- Ovarian function and disorders
- Hypothalamic control of reproductive hormones
- Reproductive Biology and Fertility
- Reproductive System and Pregnancy
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Kruppel-like factors research
- Circadian rhythm and melatonin
- Cancer-related gene regulation
- TGF-β signaling in diseases
- Plant Reproductive Biology
- Nerve injury and regeneration
- Dietary Effects on Health
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Sleep and Wakefulness Research
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
University of California, San Diego
2021-2025
Circadian (United States)
2023
Johns Hopkins University
2017-2018
Johns Hopkins Medicine
2017-2018
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...
Abstract Follicle-stimulating hormone (FSH) is necessary for fertility in both sexes as a regulator of gametogenesis and synthesis. Humans with loss-of-function mutations within the gene encoding FSH beta subunit (FSHB) are infertile. Similarly, female Fshb knock-out mice infertile fail to ovulate, males subfertile. We recently reported discovery characterization an upstream enhancer FSHB located 26 Kb transcriptional start site humans (-17 mouse) that also amplifies activin...
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...
Abstract FSH is critical for fertility. Transcription of FSHB, the gene encoding beta subunit, rate-limiting in production and regulated by both GnRH activin. Activin signals through SMAD transcription factors. Although mechanisms importance activin signaling mouse Fshb are well-established, regulation human FSHB less well understood. We previously reported a novel enhancer that contains fertility-associated single nucleotide polymorphism (rs10031006) requires region resembling full (8...
Pathogenic SRY-box transcription factor 2 (SOX2) variants typically cause severe ocular defects within a SOX2 disorder spectrum that includes hypogonadotropic hypogonadism. We examined exome-sequencing data from large, well-phenotyped cohort of patients with idiopathic hypogonadism (IHH) for pathogenic to investigate the underlying and its associated phenotypes. identified 8 IHH individuals harboring heterozygous variable These variant proteins were tested in vitro determine whether causal...
Abstract Disclosure: J. Cassin: None. D.L. Keefe: K.E. Sung: C.C. Bojo: G. Santiago: L. Plummer: K.B. Salnikov: S.B. Seminara: R. Balasubramania: P.L. Mellon: Isolated Hypogonadotropic Hypogonadism (IHH) is a condition marked by absent pubertal development and low sex steroids in the setting of low/normal gonadotropins. Mutations known IHH genes only explain <50% genetic etiology suggesting significant missing heritability IHH. To explore this heritability, we examined whole exome...
The increasing prevalence of obesity makes it important to increase the understanding maturation and function neuronal integrators regulators metabolic function. Behavioral, molecular, physiological analyses transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using Synapsincreallele. Conditional deletion homeodomain transcription factor Six3 causes dwarfism weakens circadian wheel-running activity rhythms but increases general at night, improves function, without impacting...
Abstract Disclosure: J. Cassin: None. R.D. Nguyen: K.J. Tonsfeldt: G.A. Dunn: V. Chen: S.E. Yeo: P.L. Mellon: Mutations in the SOX2 gene have been previously linked to a syndromic form of Isolated Hypogonadotropic Hypogonadism (IHH), with additional ocular and neurodevelopmental phenotypes. Recently, we published research detailing novel variants SOX2, which demonstrated functional role for Kisspeptin-expressing hypothalamic neurons, establishing mechanistic relationship between heterozygous...