A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Elevated chorionic gonadotropic hormone in transgenic mice induces parthenogenetic activation and ovarian teratomas
Tekijät: Rulli Susana B, Ahtiainen Petteri, Ratner Laura D, Jonas Kim, Calandra Ricardo S, Poutanen Matti, Huhtaniemi Ilpo
Kustantaja: Elsevier
Julkaisuvuosi: 2024
Journal: Molecular and Cellular Endocrinology
Tietokannassa oleva lehden nimi: Molecular and Cellular Endocrinology
Artikkelin numero: 112214
Vuosikerta: 587
ISSN: 0303-7207
eISSN: 1872-8057
DOI: https://doi.org/10.1016/j.mce.2024.112214
Verkko-osoite: https://doi.org/10.1016/j.mce.2024.112214
Tiivistelmä
Both male and female reproductive functions are impacted by altered gonadotrophin secretion and action, which may also influence the development of endocrine tumours. To ascertain if chronic hypersecretion of human chorionic gonadotropin (hCG) contributes to the development of gonadal tumours, double transgenic (TG) mice that overexpress hCGα- and β-subunits were analysed. By the age of two months, ovarian tumours with characteristics of teratomas developed with 100% penetrance. Teratomas were also seen in wild-type ovaries orthotopically transplanted into TG mice, demonstrating an endocrine/paracrine mechanism for the hCG-induced ovarian tumorigenesis. Both in vitro and in vivo experiments showed oocyte parthenogenetic activation in TG females. In addition, ovaries showed reduced ovulatory gene expression, inhibited ERK1/2 phosphorylation, and impaired cumulus cell expansion. Hence, persistently high endocrine hCG activity causes parthenogenetic activation and development of ovarian teratomas, along with altered follicle development and impaired ERK1/2 signalling, offering a novel mechanism associated with the molecular pathogenesis of ovarian teratomas.
Both male and female reproductive functions are impacted by altered gonadotrophin secretion and action, which may also influence the development of endocrine tumours. To ascertain if chronic hypersecretion of human chorionic gonadotropin (hCG) contributes to the development of gonadal tumours, double transgenic (TG) mice that overexpress hCGα- and β-subunits were analysed. By the age of two months, ovarian tumours with characteristics of teratomas developed with 100% penetrance. Teratomas were also seen in wild-type ovaries orthotopically transplanted into TG mice, demonstrating an endocrine/paracrine mechanism for the hCG-induced ovarian tumorigenesis. Both in vitro and in vivo experiments showed oocyte parthenogenetic activation in TG females. In addition, ovaries showed reduced ovulatory gene expression, inhibited ERK1/2 phosphorylation, and impaired cumulus cell expansion. Hence, persistently high endocrine hCG activity causes parthenogenetic activation and development of ovarian teratomas, along with altered follicle development and impaired ERK1/2 signalling, offering a novel mechanism associated with the molecular pathogenesis of ovarian teratomas.
Turun yliopiston Tutkimustietojärjestelmän portaali