Overexpression of Uromodulin-like1 accelerates follicle depletion and subsequent ovarian degeneration. Academic Article uri icon

Overview

abstract

  • Murine Uromodulin-like 1 (Umodl1) encodes Ca(2+)-dependent EGF-like membrane-bound proteins. This study presents its novel expression in the immune and female reproductive systems. Upon stimulation by CD3/CD28 antibodies, Umodl1 showed a prompt and robust response in the proliferating CD4(+) T cells, suggesting its implication in immune defense against pathogens. In ovary, Umodl1 is regulated by gonadotropins. Mice carrying extra copies of functional Umodl1 were generated by BAC transgenesis. Defects in the female reproductive system became evident from 4 months of age, manifested by reduced or diminished fertility. Histology revealed that the ovaries contained very few discernible follicles in the cortical region, and were devoid of distinguishable corpus lutea (CL). Among the multilayered preantral follicles, elevated apoptosis was observed in both the oocytes and surrounding granulosa cells (GCs). Furthermore, a high level of PPARĪ³ indicated an abnormal adipogenesis in the mutant ovaries, which resulted in the conversion of GCs into adipocytes. By 6 months of age, all mutant mice became anovulatory. Ovarian tissues including CL, follicles of various stages and associated stromal cells were degenerated. Altered expression of AMH, follicle-stimulating hormone and other ovary-specific marker genes such as Gdf-9, Rnf35, NOHLH and Gcx-1 further demonstrated that the molecular properties of the mutant ovaries have been severely disturbed. This work presents a novel animal model for investigating the pathogenesis of premature ovarian failure or early ovarian ageing.

publication date

  • November 29, 2012

Research

keywords

  • Apoptosis
  • Calcium-Binding Proteins
  • Membrane Proteins
  • Ovarian Follicle
  • Primary Ovarian Insufficiency

Identity

PubMed Central ID

  • PMC3542605

Scopus Document Identifier

  • 84870492989

Digital Object Identifier (DOI)

  • 10.1038/cddis.2012.169

PubMed ID

  • 23190605

Additional Document Info

volume

  • 3

issue

  • 11