4.7 Article

Targeted disruption of galectin 3 in mice delays the first wave of spermatogenesis and increases germ cell apoptosis

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 7, Pages 3621-3635

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03757-2

Keywords

Galectin 3; Testis; Spermatogenesis; Sertoli cell maturation; Leydig cells; Apoptosis

Funding

  1. China Scholarship Council
  2. Medical Faculty of Justus-Liebig University
  3. Deutsche Forschungsgemeinschaft (DFG) [BL1115/2-1]
  4. Heisenberg Program [BL1115/3-1-BL1115/7-1]

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Galectin 3 plays a crucial role in testicular physiology by regulating spermatogenesis initiation and testosterone biosynthesis, which ultimately affects testicular weight and reproductive function. Through its involvement in preventing germ cell apoptosis and controlling testosterone production, Galectin 3 serves as a key factor in the development of germ cells and steroidogenesis, offering potential biomarkers for testicular function.
Galectin 3 is a multifunctional lectin implicated in cellular proliferation, differentiation, adhesion, and apoptosis. This lectin is broadly expressed in testicular somatic cells and germ cells, and is upregulated during testicular development. Since the role of galectin 3 in testicular function remains elusive, we aimed to characterize the role of galectin 3 in testicular physiology. We found that galectin 3 transgenic mice (Lgals3(-/-)) exhibited significantly decreased testicular weight in adulthood compared to controls. The transgenic mice also exhibited a delay to the first wave of spermatogenesis, a decrease in the number of germ cells at postnatal day 5 (P5) and P15, and defective Sertoli cell maturation. Mechanistically, we found that Insulin-like-3 (a Leydig cell marker) and enzymes involved in steroid biosynthesis were significantly upregulated in adult Lgals3(-/-) testes. These observations were accompanied by increased serum testosterone levels. To determine the underlying causes of the testicular atrophy, we monitored cellular apoptosis. Indeed, adult Lgals3(-/-) testicular cells exhibited an elevated apoptosis rate that is likely driven by downregulated Bcl-2 and upregulated Bax and Bak expression, molecules responsible for live/death cell balance. Moreover, the percentage of testicular macrophages within CD45(+) cells was decreased in Lgals3(-/-) mice. These data suggest that galectin 3 regulates spermatogenesis initiation and Sertoli cell maturation in part, by preventing germ cells from undergoing apoptosis and regulating testosterone biosynthesis. Going forward, understanding the role of galectin 3 in testicular physiology will add important insights into the factors governing the development of germ cells and steroidogenesis and delineate novel biomarkers of testicular function.

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