FOXA2 regulates endoplasmic reticulum stress, oxidative stress, and apoptosis in spermatogonial cells by the Nrf2

Related Experiment Video

Updated: Jun 4, 2025

Analysis of Oxidative Stress in Zebrafish Embryos
11:05

Analysis of Oxidative Stress in Zebrafish Embryos

Published on: July 7, 2014

37.1K

Weiwei Li1, Xiurong Yin1, Lei Zhang2

  • 1Department of Reproductive Medicine, Qinhuangdao Maternal and Child Health Hospital, Qinhuangdao, China.

Experimental Cell Research
|December 19, 2024
PubMed

Insights

Forkhead box A2 (FOXA2) protects male reproductive cells from hypoxia-induced damage. This study reveals FOXA2

Area of Science:

  • Reproductive Biology
  • Cellular Stress Response
  • Molecular Mechanisms of Infertility

Background:

  • Hypoxia significantly impairs spermatogenesis, a key factor in male infertility.
  • Forkhead box A2 (FOXA2) is crucial for spermatogenesis and abundant in spermatogonial stem cells.

Purpose of the Study:

  • To investigate the protective role of FOXA2 in spermatogonial cells against hypoxia.
  • To elucidate the molecular pathways involved in FOXA2-mediated protection.

Main Methods:

  • Investigated FOXA2 expression in hypoxia-stimulated spermatogonial cells.
  • Utilized FOXA2 overexpression and Nrf2 knockdown in cell models.
  • Assessed endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis markers.
  • Analyzed the Nrf2/HO-1 signaling pathway.

Main Results:

  • FOXA2 expression decreased under hypoxia; its overexpression mitigated ER stress, oxidative stress, and apoptosis.
  • FOXA2 overexpression reduced MDA levels and increased antioxidant enzyme activities (SOD, CAT, GSH-Px).
  • FOXA2 prevented hypoxia-induced inactivation of the Nrf2 pathway, which was critical for its protective effects.

Conclusions:

  • FOXA2 protects spermatogonial cells from hypoxia-induced damage by regulating ER stress, oxidative stress, and apoptosis via the Nrf2/HO-1 pathway.
  • FOXA2 represents a potential therapeutic target for male infertility associated with impaired spermatogenesis due to hypoxia.
Keywords:
ApoptosisEndoplasmic reticulum stressFOXA2Male infertilityOxidative stressSpermatogenesis

More Related Videos

Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.8K
Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

18.0K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.3K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
10.5K