# Defining the Mechanism of Meiotic Initiation Through Autophagy Pathway

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $155,000

## Abstract

PROJECT SUMMARY
The ovary is not only a reproductive organ but also an endocrine organ that produces hormones, including
estrogen, testosterone, and progesterone—which are vital to women’s reproductive organ, breast development,
bone health, and pregnancy. Thus, the ovary is critical to women’s fertility and health. Inside the ovary, ovarian
follicles (oocytes enclosed by granulosa cells) are the basic functional unit. However, early depletion of oocytes
is a major cause of primary ovarian insufficiency (POI), which affects 5-10% women worldwide. Oogenesis
(formation of oocytes) in women starts during fetal development, when primordial germ cells (PGCs) exit mitosis
and enter meiotic prophase I (a process termed “meiotic initiation”) to carry out homologous recombination. This
is in contrast with spermatogenesis, which does not occur upon puberty in men. At birth, the ovary is filled with
meiotically arrested oocytes in follicle structures. Meiotic initiation is essential for oocyte formation, in that genetic
disruption of this process results in a near-complete loss of oocytes in adult ovaries. Additionally, during meiotic
prophase I, defective homologous recombination results in meiotic chromosome segregation errors and oocytes
carrying an incorrect number of chromosomes (aneuploidy), a leading cause of poor pregnancy and fetal
outcomes. Thus, proper meiotic initiation ensures both the quantity and the quality of oocytes. However, the
molecular mechanism underlying meiotic initiation is poorly understood. We have reported that stimulated by
retinoic acid gene 8 (STRA8), a gatekeeper of meiotic initiation in vertebrates, acts as a suppressor of autophagy.
As such, loss of STRA8 results in an uncontrolled autophagy activation in germ cells during both
spermatogenesis and oogenesis. Based on this information, the parent grant studies autophagic regulation of
meiotic initiation in the context of spermatogenesis. Our hypothesis is that STRA8-mediated suppression of
autophagy allows accumulation of proteins required for meiotic gene activation and initiation; in the absence of
STRA8, these proteins are degraded by autophagy, precluding meiosis. This Administrative Supplement extends
our study from spermatogenesis to oogenesis. We will: 1. Investigate the role of autophagy suppression in
meiotic initiation in fetal ovaries; 2. Define the molecular links between autophagy and meiotic initiation in fetal
ovaries. Aberrant autophagy due to genetic or environmental causes is often linked to human diseases.
Meanwhile, autophagy pathway represents an intriguing druggable target. Thus, upon completion, knowledge
gained from Administrate Supplement may provide insights into the etiology of POI from the perspective of
autophagy dysregulation and offer novel pretherapeutic opportunities to improve women’s health.

## Key facts

- **NIH application ID:** 10556093
- **Project number:** 3R01HD103888-03S1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Ning Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $155,000
- **Award type:** 3
- **Project period:** 2020-09-22 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556093

## Citation

> US National Institutes of Health, RePORTER application 10556093, Defining the Mechanism of Meiotic Initiation Through Autophagy Pathway (3R01HD103888-03S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10556093. Licensed CC0.

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