Related Experiment Video
Updated: Jun 25, 2026
09:08
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Mutations in NR5A1 associated with ovarian insufficiency
Diana Lourenço1, Raja Brauner, Lin Lin
1Human Developmental Genetics, Institut Pasteur, Paris, France.
The New England Journal of Medicine
|February 28, 2009
Summary
Mutations in the NR5A1 gene are linked to primary ovarian insufficiency in females (46,XX) and disorders of sex development in males (46,XY). This discovery sheds light on the genetic causes of these reproductive conditions.
Area of Science:
- Genetics
- Endocrinology
- Reproductive Biology
Background:
- The genetic underpinnings of nonsyndromic ovarian insufficiency remain largely unidentified.
- NR5A1 (steroidogenic factor 1) is a critical nuclear receptor regulating the hypothalamic-pituitary-steroidogenic axis.
- While NR5A1 mutations cause 46,XY disorders of sex development, its role in ovarian function is increasingly suggested by mouse studies.
Purpose of the Study:
- To investigate the hypothesis that NR5A1 gene mutations contribute to ovarian development and function disorders.
- To identify mutations in NR5A1 in families with both 46,XY disorders of sex development and 46,XX primary ovarian insufficiency, as well as in sporadic cases of ovarian insufficiency.
Main Methods:
- Sequencing of the NR5A1 gene in affected individuals from four families and 25 subjects with sporadic ovarian insufficiency.
- Functional studies to assess the impact of identified mutations on NR5A1 transactivational activity.
- Analysis of mutation prevalence in over 700 control alleles.
Main Results:
- Mutations in the NR5A1 gene were identified in members of all four families and in 2 of 25 subjects with isolated ovarian insufficiency.
- Detected mutations included in-frame deletions, frameshift, and missense variants, all significantly impairing NR5A1 function.
- These NR5A1 mutations were associated with 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency, and were absent in controls.
Conclusions:
- Mutations in the NR5A1 gene are a cause of 46,XX primary ovarian insufficiency.
- NR5A1 mutations are also associated with 46,XY disorders of sex development.
- This research establishes a direct link between NR5A1 dysfunction and specific reproductive developmental disorders.
Related Concept Videos
02:07Oogenesis
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
02:55The Nucleolus
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
01:21Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:28Infertility in Females
Female infertility is defined as the inability to conceive after a year of regular, unprotected intercourse and affects about 10–15% of couples worldwide. The primary cause of female infertility is ovulatory disorders, which hinder the release of eggs. These disorders can be classified as hypothalamic amenorrhea, polycystic ovarian syndrome (PCOS), premature ovarian failure, and hyperprolactinemic anovulation disorders.
Endometriosis, a condition characterized by abnormal growth of endometrial...
Endometriosis, a condition characterized by abnormal growth of endometrial...