Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice
| العنوان: | Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice |
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| المؤلفون: | Haojiang Lu, Qiaolin Deng, Elisabet Stener-Victorin, Maria Manti, Eva Lindgren, Sonja Edström, Claes Ohlsson, Elisabet Jerlhag, Anna Benrick, Sanjiv Risal, Han-Pin Pui |
| المصدر: | The FASEB Journal. 34:14440-14457 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| وصف الملف: | application/pdf |
| تدمد: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202001060r |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::809d53b20640f2aa4e7344bde54ae6a5 https://doi.org/10.1096/fj.202001060r |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....809d53b20640f2aa4e7344bde54ae6a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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| DOI: | 10.1096/fj.202001060r |