# Defining the Mechanism of Meiotic Initiation Through Autophagy Pathway

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $326,585

## Abstract

PROJECT SUMMARY
Poor sperm quantity and quality are major causes of male infertility, affecting ~7% of men worldwide. Male fertility
depends on the conversion of diploid germ cells (spermatogonia) into haploid spermatozoa (sperm). Meiotic
initiation, a defining step in this process, revolves around the transition from mitotic to meiotic cell cycles and
entails activation of meiotic genes required for the chromosomal events of meiosis prophase I. To date, a best
characterized gatekeeper of meiotic initiation in mammals is stimulated by retinoic acid gene 8 (Stra8), in that
Stra8P–/–P germ cells fail to express a subset of meiotic genes and do not enter meiosis. Our recent work indicates
a novel molecular role of STRA8 as a suppressor of autophagy, suggesting a novel link between meiotic initiation
and autophagy, a protein and cellular organelle degradation process. Based on this information, we hypothesize
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.
To test our hypothesis, we will: 1) investigate the role of autophagy in STRA8-mediated meiotic initiation. 2)
define the molecular links between autophagy and meiotic initiation. Together, our study will establish autophagy
as a yet unrecognized regulator of meiotic initiation and uncover autophagy-sensitive proteins that serve as
essential molecular steps during this process in mammals. By developing a better understanding of autophagy
as a barrier to meiotic induction, our study will offer a significant technical advancement for in vitro gamete
production. Ultimately, translation of our study may identify novel therapeutic targets in the autophagy pathway
for male infertility or contraception treatment.

## Key facts

- **NIH application ID:** 10437882
- **Project number:** 5R01HD103888-03
- **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:** $326,585
- **Award type:** 5
- **Project period:** 2020-09-22 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437882

## Citation

> US National Institutes of Health, RePORTER application 10437882, Defining the Mechanism of Meiotic Initiation Through Autophagy Pathway (5R01HD103888-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437882. Licensed CC0.

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