Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Eric Nilsson; Gretchen Dole; Michael K Skinner

doi:10.1530/REP-09-0179

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Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Journal article

Open access

Peer reviewed

Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Eric Nilsson, Gretchen Dole and Michael K Skinner

Reproduction (Cambridge, England), Vol.138(4), pp.697-707

10/2009

DOI: https://doi.org/10.1530/REP-09-0179

Handle:

https://hdl.handle.net/2376/103607

PMCID: PMC5728087

PMID: 19584175

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Abstract

Animals, Newborn

Granulosa Cells - physiology

Oocytes - metabolism

Cells, Cultured

Nerve Growth Factor - pharmacology

Ovary - physiology

Rats, Sprague-Dawley

Granulosa Cells - drug effects

Granulosa Cells - metabolism

Gene Expression Regulation - drug effects

Brain-Derived Neurotrophic Factor - pharmacology

Ovarian Follicle - drug effects

Oocytes - physiology

Stem Cell Factor - pharmacology

Ovarian Follicle - physiology

Oocytes - drug effects

Ovary - drug effects

Neurotrophin 3 - pharmacology

Ovarian Follicle - metabolism

Ovary - metabolism

Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100-250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition.

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Title: Neurotrophin NT3 promotes ovarian primordial to primary follicle transition
Creators: Eric Nilsson - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4234, USA
Gretchen Dole
Michael K Skinner
Publication Details: Reproduction (Cambridge, England), Vol.138(4), pp.697-707
Academic Unit: Biological Sciences, School of
Publisher: Bioscientifica Ltd; England
Number of pages: 11
Grant note: R01 HD048898 / NICHD NIH HHS
Identifiers: 99900546565201842
Language: English
Resource Type: Journal article