A1 Refereed original research article in a scientific journal
Elevated chorionic gonadotropic hormone in transgenic mice induces parthenogenetic activation and ovarian teratomas
Authors: Rulli Susana B, Ahtiainen Petteri, Ratner Laura D, Jonas Kim, Calandra Ricardo S, Poutanen Matti, Huhtaniemi Ilpo
Publisher: Elsevier
Publication year: 2024
Journal: Molecular and Cellular Endocrinology
Journal name in source: Molecular and Cellular Endocrinology
Article number: 112214
Volume: 587
ISSN: 0303-7207
eISSN: 1872-8057
DOI: https://doi.org/10.1016/j.mce.2024.112214
Web address : https://doi.org/10.1016/j.mce.2024.112214
Self-archived copy’s web address: https://kclpure.kcl.ac.uk/ws/files/268939671/MCE_2024-_Rulli_et_al.pdf
Abstract
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.
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