Targeted disruption of galectin 3 in mice delays the first wave of spermatogenesis and increases germ cell apoptosis
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Targeted disruption of galectin 3 in mice delays the first wave of spermatogenesis and increases germ cell apoptosis. / Lei, Tao; Blois, Sandra M; Freitag, Nancy; Bergmann, Martin; Bhushan, Sudhanshu; Wahle, Eva; Huang, Annie Chi-Chun; Chen, Hung-Lin; Hartmann, Michaela F; Wudy, Stefan A; Liu, Fu-Tong; Meinhardt, Andreas; Fijak, Monika.
in: CELL MOL LIFE SCI, Jahrgang 78, Nr. 7, 04.2021, S. 3621-3635.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Targeted disruption of galectin 3 in mice delays the first wave of spermatogenesis and increases germ cell apoptosis
AU - Lei, Tao
AU - Blois, Sandra M
AU - Freitag, Nancy
AU - Bergmann, Martin
AU - Bhushan, Sudhanshu
AU - Wahle, Eva
AU - Huang, Annie Chi-Chun
AU - Chen, Hung-Lin
AU - Hartmann, Michaela F
AU - Wudy, Stefan A
AU - Liu, Fu-Tong
AU - Meinhardt, Andreas
AU - Fijak, Monika
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
U2 - 10.1007/s00018-021-03757-2
DO - 10.1007/s00018-021-03757-2
M3 - SCORING: Journal article
C2 - 33507326
VL - 78
SP - 3621
EP - 3635
JO - CELL MOL LIFE SCI
JF - CELL MOL LIFE SCI
SN - 1420-682X
IS - 7
ER -
