# Genetics and Genomics of the Ovarian Reserve and Female Fertility

> **NIH NIH R01** · JACKSON LABORATORY · 2021 · $412,306

## Abstract

PROJECT SUMMARY/ABSTRACT
Personalized reproductive medicine will ultimately be realized with patient-tailored infertility treatments and
fertility preservation planning. However the development of predictive genetic tests for women is hampered by
the complex etiology of important fertility factors, such as the ovarian reserve. The ovarian reserve constitutes
the capacity of ovaries to produce viable, fertilizable oocytes. Deficiencies in the ovarian reserve can lead to
infertility, and an increased incidence of miscarriages, birth defects and premature ovarian failure. Thousands
of genes are involved in mammalian reproduction, and infertility likely arises from deleterious combinations of
multiple alleles, rather than single gene defects, making the identification of causative polymorphisms that
much more challenging in large-scale human genetic studies. Thus, appropriate genetic models must be
developed to identify genetic factors and their profiles that reflect reproductive traits and risks inherent to
diverse populations. Our overarching hypothesis is that multiple genetic factors regulating oocyte
development determine differences in the ovarian reserve among genetically diverse individuals and
that defined genetic profiles can be used to predict the risk of ovarian reserve deficiencies and
subsequent fertility issues in women. We propose two complimentary studies using ovarian phenotyping
and quantitative trait loci mapping in genetically heterogeneous mice from the Collaborative Cross (CC) and
Diversity Outbred (DO) programs. The CC, comprised of diverse inbred lines, is optimal for longitudinal studies
of oocyte development; while the DO, comprised of many single genetically unique individuals, is ideal for high
precision mapping of genetic variants regulating ovarian reserve. Aim 1 will determine how genetic variation
affects early oocyte development and contributes to differences in oocyte numbers and quality in mice
with different genetic backgrounds. We will phenotype CC mice for reproductive traits including meiotic
recombination, fetal and perinatal oocyte loss, primordial follicle formation and the size of the ovarian reserve.
These experiments will define genetic profiles linked to specific deficiencies in oocyte development and
generate a phenotyped collection of models for the development of new diagnostic tools and treatment
methods. We will refine the list of potential genes and gene networks linked to ovarian deficiencies in Aim 2,
where we will identify genetic variants underlying variation in ovarian reserve size using DO mice. We
will perform quantitative trait loci mapping and analyze identified regions for candidate genes and non-coding
elements regulating oocyte development. This aim will deliver a list of potential genes, variants and pathways
underlying low ovarian reserve as candidates for similar conditions in women. For women with idiopathic
infertility, those postponing child bearing and pediatric cancer patients u...

## Key facts

- **NIH application ID:** 10133467
- **Project number:** 5R01HD093778-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Ewelina M Bolcun-Filas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,306
- **Award type:** 5
- **Project period:** 2018-06-11 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133467

## Citation

> US National Institutes of Health, RePORTER application 10133467, Genetics and Genomics of the Ovarian Reserve and Female Fertility (5R01HD093778-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133467. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*