RNA regulation in germline development and fertility

NIH RePORTER · NIH · R35 · $470,347 · view on reporter.nih.gov ↗

Abstract

Our research team explores genetic, molecular, and cellular interactions between germ cells and somatic (non-germline) cells of the gonad. We focus on the mechanisms regulating reproductive system formation and function. Key questions are: 1) how are germline stem cells (GSCs) established and why are they absent in women? and 2) what establishes and maintains the sex-specific identity of germ cells, gonadal and extragonadal somatic cells, all of which are required for reproductive success and species perpetuation. Our goal in pursuing this research program is to define the developmental mechanisms regulating gonadogenesis to prevent infertility and to extend reproductive opportunities and choices for women and their partners. Extending reproductive potential is not only central to population preservation and fulfilling dreams of parenthood, it will also mitigate or eliminate health risks that accompany premature ovarian failure, perimenopause, and menopause in many women. From a developmental perspective, disorders of sexual development (DSDs) are common, and include gonadal dysgenesis, dysregulated puberty, gender dysphoria, and sterility, thereby posing challenging sex-specific treatment decisions. DSDs are idiopathic or result from genetic or hormonal anomalies during sexual development. With humans living longer and delaying parenthood, declining reproductive potential and increased germline mutation burden affect all sexes. We will leverage powerful genetic tools, cell imaging, and genome-wide multi-omics approaches to unravel the cellular and molecular underpinnings of reproductive development, health, and fertility, largely neglected areas of biomedical research.

Key facts

NIH application ID
10842759
Project number
1R35GM153244-01
Recipient
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Principal Investigator
Florence Louise Marlow
Activity code
R35
Funding institute
NIH
Fiscal year
2024
Award amount
$470,347
Award type
1
Project period
2024-08-02 → 2029-07-31