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Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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2020 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 34, no 11, p. 14440-14457Article in journal (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
John Wiley & Sons, 2020. Vol. 34, no 11, p. 14440-14457
Keywords [en]
adipose tissue, imprinting, polycystic ovary syndrome, sex steroids, sympathetic activity
National Category
Physiology Obstetrics, Gynecology and Reproductive Medicine
Research subject
Translational Medicine TRIM
Identifiers
URN: urn:nbn:se:his:diva-19068DOI: 10.1096/fj.202001060RISI: 000568293000001PubMedID: 32892421Scopus ID: 2-s2.0-85090221868OAI: oai:DiVA.org:his-19068DiVA, id: diva2:1468100
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CC BY-NC-ND 4.0

Available from: 2020-09-17 Created: 2020-09-17 Last updated: 2023-09-26Bibliographically approved

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Benrick, Anna

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