# Hormonal Regulation Sertoli Cell Maturation

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2024 · $431,440

## Abstract

Project Summary/Abstract:
The cycle of the seminiferous epithelium is a characteristic of spermatogenesis in mammals. The cycle serves
to distribute the developmental stages of spermatogenesis in constant periodic intervals along the seminiferous
tubules. The function of the cycle is to assure a constant source of spermatozoa over the relatively extended
developmental time period. We have previously shown in the mouse testis that the cycle is initiated by pulses
of retinoic acid (RA) originally generated by the Sertoli cells at stages VIII and IX of the cycle. The pulse of RA
forces the undifferentiated spermatogonia to irreversibly enter the differentiation pathway. At stages VIII and
IX we have shown in the adult mouse that the Sertoli cells demonstrate an increased abundance of hundreds
of transcripts that allow for multiple functions such as RA synthesis, junction formation, uptake of residual
bodies, spermiation, and others. In the absence of germ cells there are no cyclic activities of Sertoli cells
detectable along the tubules, thus, accentuating the requirement for interactions between Sertoli and germ
cells for normal spermatogenesis. We propose to examine the influence of spermatogonia at stages VIII and
IX on the transcriptome of Sertoli cells and their functions during the development of complete
spermatogenesis. We propose that this influence on the transcriptome and on the generation of the RA pulse
is partially or wholly a result of Sertoli-germ cell interactions through the Notch signaling pathway. We will test
this hypothesis by examining the influence of germ cells with Notch ligand gene deletions on the transcriptome
and RA biosynthesis in normally developing Sertoli cells and in Sertoli cells with Notch receptor deletions. We
will utilize a new technology designated capped small RNAseq or nTIseq to obtain information on active
promoters and transcriptional start sites in the presence and absence of an intact Notch signaling pathway.
We will pay special attention to transcripts regulating RA biosynthesis such as RDH10. The results of this
study will clarify the interactive roles of germ and somatic cells in spermatogenesis and possibly implicate the
Notch pathway in the etiology of male infertility.

## Key facts

- **NIH application ID:** 10878501
- **Project number:** 2R01HD010808-45A1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** MICHAEL D GRISWOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $431,440
- **Award type:** 2
- **Project period:** 1977-08-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878501

## Citation

> US National Institutes of Health, RePORTER application 10878501, Hormonal Regulation Sertoli Cell Maturation (2R01HD010808-45A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10878501. Licensed CC0.

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