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Reduced Akr1b7 signaling drives ovarian aging and reproductive dysfunction

Keishiro Isayama1,2, Kenji Watanabe1, Masato Ohtsuka3

  • 1Institute of Gene Research, Yamaguchi University Science Research Center, Yamaguchi 755-8505, Japan.

Iscience
|February 23, 2026
PubMed

Insights

The Aldo-keto reductase Akr1b7 pathway is crucial for female fertility. Its absence in older mice leads to impaired ovarian function and reduced reproductive success.

Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Natural ovarian aging leads to a progressive decline in female fertility.
  • Understanding the molecular mechanisms underlying age-related fertility decline is critical.

Purpose of the Study:

  • To investigate the role of the Aldo-keto reductase Akr1b7 (Akr1b7) pathway in ovarian aging and female reproductive function.
  • To identify molecular factors contributing to age-associated fertility loss.

Main Methods:

  • Comprehensive RNA expression analysis in aging mouse ovaries during the estrous cycle.
  • Phenotypic analysis of Akr1b7 knockout (Akr1b7-/-) mice, including oocyte maturation, follicular development, and reproductive parameters.
  • Hormone level assessment and gene expression analysis of key steroidogenic enzymes.

Main Results:

  • The transient Akr1b7 pathway activation observed in young mice was absent in older mice.
  • Akr1b7-/- mice showed attenuated oocyte Akt activation, impaired follicular development, and increased immature ovulated oocytes.
  • Akr1b7 deficiency resulted in an extended estrous cycle due to prolonged diestrous stage and sustained progesterone levels.
  • Reduced Cyp17a1 expression, a progesterone-metabolizing enzyme, was observed in the theca cells of Akr1b7-/- mice.

Conclusions:

  • Akr1b7 acts as a key regulator of ovarian signaling, hormone homeostasis, and reproductive function.
  • Disruption of the Akr1b7 pathway mimics phenotypes associated with declining fertility in aging females.
  • Restoring Akr1b7 pathway function may offer therapeutic potential for age-related infertility.
Keywords:
Endocrine regulationEndocrine system physiologyEndocrinologyFemale reproductive endocrinologyHealth sciences

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