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Irisin deletion induces a decrease in growth and fertility in mice.

Yunyao Luo1,2,3,4, Xiaoyong Qiao1,2,3,4, Yaxian Ma1,2,3,4

  • 1Reproductive Endocrinology and Regulation Laboratory West China Second University Hospital, Sichuan University, #20 Section 3, Ren Min Nan Road, Chengdu, 610041, Sichuan, China.

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Mice lacking irisin (a protein from Fndc5) showed poor growth, reduced fertility, and disordered hormone levels. Irisin influences ovarian gene expression and steroid hormone production, impacting mammalian reproduction.

Keywords:
Growth and developmentHormone metabolismIrisinReproduction

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Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Metabolism

Background:

  • Irisin, derived from fibronectin type III domain-containing protein 5 (Fndc5), is crucial for energy homeostasis.
  • The interplay between energy metabolism and reproductive functions is established, yet irisin's reproductive roles are understudied.

Purpose of the Study:

  • To investigate the biological functions of irisin in mammalian reproduction.
  • To elucidate the effects of irisin deficiency on female reproductive parameters and ovarian function.
  • To explore irisin's impact on steroid hormone synthesis in the ovary.

Main Methods:

  • Generation of Fndc5 gene-mutant mice to create irisin-deficient models.
  • Assessment of survival rates, body weight, fertility, estrus cycles, and ovarian follicle development.
  • Measurement of serum steroid hormone levels via ELISA and ovarian gene expression using mRNA sequencing.
  • In vitro study of exogenous irisin's effects on steroid hormone production in KGN cells.

Main Results:

  • Irisin deficiency led to increased mortality, reduced body weight, and impaired fertility in mice.
  • Mutant mice exhibited irregular estrus cycles, fewer antral follicles, and altered sex hormone profiles (decreased estradiol, FSH, LH; increased progesterone).
  • Ovarian expression of steroidogenesis-related genes (Akr1c18, Mamld1, Cyp19a1) was reduced in irisin-deficient mice.
  • Exogenous irisin treatment in KGN cells stimulated estradiol production and inhibited progesterone secretion.

Conclusions:

  • Irisin deficiency disrupts endocrine metabolism, leading to impaired growth, development, and fertility in mice.
  • Irisin plays a significant role in regulating ovarian gene expression and steroid hormone production.
  • This research highlights irisin's potential involvement in mammalian reproductive processes.