Related Experiment Video

Updated: Jul 8, 2026

Germ Cell Transplantation and Testis Tissue Xenografting in Mice
10:41

Germ Cell Transplantation and Testis Tissue Xenografting in Mice

Published on: February 6, 2012

PRMT5 inhibition promotes cross-species spermatogonia expansion and suppresses differentiation

Zhaokai Yao1, Wen Wang2, Kang Tang2

  • 1Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.

Cell Regeneration (London, England)
|July 6, 2026
PubMed

Insights

Inhibiting PRMT5 (protein arginine methyltransferase 5) prevents mouse, human, and primate spermatogonial stem cells (SSCs) from differentiating in vitro. This offers a new method for culturing SSCs for fertility treatments.

Area of Science:

  • Reproductive Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Spermatogonial stem cells (SSCs) are crucial for male fertility but difficult to maintain in an undifferentiated state in vitro.
  • Clinical applications of SSCs are limited by the lack of effective methods for their long-term culture.
  • Epigenetic regulators involved in differentiation are potential targets for controlling SSC state.

Purpose of the Study:

  • To identify and target epigenetic regulators that promote SSC differentiation.
  • To evaluate the efficacy of PRMT5 inhibition in maintaining SSC undifferentiation and proliferation in vitro.
  • To explore the potential of PRMT5 inhibition for therapeutic applications in male infertility.

Main Methods:

  • Conducted a small-molecule screen targeting conserved epigenetic regulators upregulated during SSC differentiation.
  • Utilized in vitro culture systems with GDNF-deficient microenvironments to promote differentiation.
  • Administered EPZ015666, a PRMT5 inhibitor, to mouse, human, and non-human primate spermatogonia.
  • Performed SSC transplantation assays to assess the retention of spermatogonial identity.
  • Investigated the mechanism of action by examining PRMT5 enzymatic activity.

Main Results:

  • PRMT5 inhibition by EPZ015666 suppressed mouse SSC differentiation and enhanced their proliferation in vitro.
  • EPZ015666-treated SSCs maintained their identity, as confirmed by transplantation assays.
  • The differentiation-inhibitory effect was reversible upon drug withdrawal, restoring spermatogenesis.
  • EPZ015666 also inhibited differentiation and promoted proliferation of human and non-human primate spermatogonia.
  • The mechanism involved direct inhibition of PRMT5's enzymatic active site.

Conclusions:

  • PRMT5 inhibition is a viable strategy to maintain SSCs in an undifferentiated state in vitro.
  • This approach shows promise for overcoming challenges in culturing human SSCs for clinical use.
  • PRMT5 inhibition could lead to novel therapeutic strategies for treating male infertility.
Keywords:
Cross-species validationEPZ015666Male infertilityPRMT5Spermatogonial stem cells

More Related Videos

Mouse Round Spermatid Injection08:41

Mouse Round Spermatid Injection

Published on: January 26, 2024

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model09:40

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model

Published on: February 6, 2018

Related Concept Videos

Spermatogenesis01:41

Spermatogenesis

Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male reproductive...
Spermatogenesis01:22

Spermatogenesis

Spermatogenesis is a complex process that involves the development of sperm cells from undifferentiated stem cells in the seminiferous tubules of the testes. The process is essential for the production of mature and functional sperm cells that are capable of fertilizing an egg.
The process of spermatogenesis can be divided into mitosis, meiosis, and spermiogenesis. During mitosis, the spermatogonia or stem cells divide to produce two identical daughter cells, type A and B spermatogonia. Type-A...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...