Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice

Autor: Haojiang Lu, Qiaolin Deng, Elisabet Stener-Victorin, Maria Manti, Eva Lindgren, Sonja Edström, Claes Ohlsson, Elisabet Jerlhag, Anna Benrick, Sanjiv Risal, Han-Pin Pui
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_specialty
Sympathetic Nervous System
Fysiologi
endocrine system diseases
Physiology
Dopamine
Adipose tissue
Estrous Cycle
Reproduktionsmedicin och gynekologi
Biochemistry
Fetal Development
Mice
03 medical and health sciences
Oogenesis
0302 clinical medicine
Gonocyte
Obstetrics
Gynecology and Reproductive Medicine
Internal medicine
Nerve Growth Factor
Genetics
medicine
Animals
Endocrine system
sex steroids
Molecular Biology
Cells
Cultured
Estrous cycle
Fetus
business.industry
Ovary
sympathetic activity
Polycystic ovary
female genital diseases and pregnancy complications
Up-Regulation
adipose tissue
030104 developmental biology
Endocrinology
Nerve growth factor
polycystic ovary syndrome
Female
Folliculogenesis
imprinting
business
030217 neurology & neurosurgery
Polycystic Ovary Syndrome
Biotechnology
Zdroj: The FASEB Journal. 34:14440-14457
ISSN: 1530-6860
0892-6638
Popis: Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels. The role of ovarian NGF excess in the PCOS pathophysiology and in the PCOS-related features is unclear. Here, using transgenic mice overexpressesing NGF in the ovarian theca cells (17NF mice), we assessed the female embryonic development, and the reproductive and metabolic profile in adult females. Ovarian NGF excess caused growth restriction in the female fetuses, and a delayed gonocyte and primary oocyte maturation. In adulthood, the 17NF mice displayed irregular estrous cycles and altered ovarian expression of steroidogenic and epigenetic markers. They also exhibited an increased sympathetic output with increased circulating dopamine, and metabolic dysfunction reflected by aberrant adipose tissue morphology and function, impaired glucose metabolism, decreased energy expenditure, and hepatic steatosis. These findings indicate that ovarian NGF excess leads to adverse fetal development and to reproductive and metabolic complications in adulthood, mirroring common features of PCOS. This work provides evidence that NGF excess may be implicated in the PCOS pathophysiology. CC BY-NC-ND 4.0
Databáze: OpenAIRE
Externí odkaz: