# Apoptotic dysregulation in male infertility

> **NIH NIH F32** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $8,910

## Abstract

Project Summary/Abstract
 Across species, sexual development and fertility are dependent on cell death events. In developing
ovaries and testes in mammals, massive death of germ cells (precursors of sperm and eggs) occurs during a
fetal attrition event that is presumed to prevent overproliferation and select for highest quality cells. Cell death is
also observed in males during embryonic regression of structures that form the female reproductive tract, and
morphogenesis of the pituitary gland, which regulates gonadal sex hormone production. Surprisingly, inhibition
of apoptosis results in male-specific infertility in mice, but it is not understood why this occurs or how cell death
is regulated throughout male sexual development. The goal of my research is to understand regulation of
apoptosis along the hypothalamic-pituitary-gonadal (HPG) axis throughout male sexual development, and why
disruption of apoptosis causes infertility. Specifically, this proposal aims to map apoptotic sensitivity in normal
testicular germ cells, and to find evidence of apoptotic misregulation in reproductive tissues in infertile males. In
Aim 1, the apoptotic vulnerability of germ cells at different stages of development and differentiation will be
determined using functional cell death-predictive assays and testicular irradiation to induce germ cell death. In
Aim 2, the requirement of apoptosis in male sex differentiation will be investigated by analyzing embryonic
reproductive tract development and adult HPG axis signaling in genetic models of apoptosis insufficiency.
Testicular germ cell transplantation will be used to establish contribution of germline vs. somatic testicular cell
apoptosis dysregulation to male infertility. These findings will support identification of targeted treatments for
disorders of sexual development or cytotoxic exposures affecting developing children, which lead to poor
reproductive outcomes as adults.
 The training plan for the proposed fellowship will further develop expertise in molecular and
developmental biology approaches, and address conceptual and technical inexperience in other disciplines of
reproductive science, including endocrinology and epidemiology. It will also provide the opportunity to move from
zebrafish to mice as a model of disease and development. This will be achieved by continuing education in
biostatistics, training with a co-sponsor, and utilizing an interdisciplinary scientific advisory committee to oversee
experimental design and data analysis. Responsible conduct of research training will also be undertaken in Year
1. The Harvard School of Public Health, which is committed to the multi-faceted study of reproductive health and
infertility, will strongly support this research and training plan with imaging and analytical facilities as well as
oversight of established faculty in the field. The laboratory of Kristopher Sarosiek, which excels at functional
assays of apoptosis, will enable development of a unique and...

## Key facts

- **NIH application ID:** 9991087
- **Project number:** 1F32HD102088-01
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Kaitlyn Ann Webster
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,910
- **Award type:** 1
- **Project period:** 2020-09-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991087

## Citation

> US National Institutes of Health, RePORTER application 9991087, Apoptotic dysregulation in male infertility (1F32HD102088-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991087. Licensed CC0.

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