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Updated: Jun 12, 2025

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
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Constitutive Androstane Receptor Regulates Germ Cell Homeostasis, Sperm Quality, and Male Fertility via Akt-Foxo1

Mélusine Monrose1, Hélène Holota1, Guillaume Martinez2,3

  • 1INSERM U1103, Université Clermont Auvergne, CNRS UMR-6293, GReD Institute, Team-Volle, Clermont-Ferrand, F-63001, France.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 25, 2024
PubMed

Insights

The constitutive androstane receptor (Car) is vital for male fertility. Car deficiency impairs sperm quality, leading to increased in utero offspring death, highlighting its role in reproductive health.

Area of Science:

  • Reproductive Biology
  • Toxicology
  • Molecular Endocrinology

Background:

  • Male fertility can be negatively impacted by environmental toxins.
  • The constitutive androstane receptor (Car) is involved in detoxification but its role in male fertility is not well understood.

Purpose of the Study:

  • To investigate the role of the Car signaling pathway in male fertility and its response to reprotoxicants.

Main Methods:

  • Utilized in vivo, in vitro, and pharmacological approaches in wild-type and Car-deficient mouse models.
  • Analyzed sperm quality, histone retention, and offspring viability.
  • Investigated molecular interactions involving Car, Akt, Foxo1, and histone acetylation.

Main Results:

  • Car inhibition led to impaired male fertility with reduced sperm quality, characterized by increased histone retention.
  • Histone retention was correlated with a higher percentage of in utero offspring mortality.
  • Identified key molecular interactions between Car, Akt, Foxo1, and histone acetylation.

Conclusions:

  • The Car signaling pathway is essential for maintaining germ cell homeostasis and male fertility.
  • Car plays a critical role in protecting against the adverse effects of environmental compounds on male reproductive health and offspring survival.
Keywords:
Foxo1constitutive androstane receptorrepro‐toxicityspermatogoniaxenobiotic

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