The University of Southampton
University of Southampton Institutional Repository

The APC/C activator FZR1 is essential for meiotic prophase I in mice

The APC/C activator FZR1 is essential for meiotic prophase I in mice
The APC/C activator FZR1 is essential for meiotic prophase I in mice
Fizzy-related 1 (FZR1) is an activator of the Anaphase promoting complex/cyclosome (APC/C) and an important regulator of the mitotic cell division cycle. Using a germ-cell-specific conditional knockout model we examined its role in entry into meiosis and early meiotic events in both sexes. Loss of APC/CFZR1 activity in the male germline led to both a mitotic and a meiotic testicular defect resulting in infertility due to the absence of mature spermatozoa. Spermatogonia in the prepubertal testes of such mice had abnormal proliferation and delayed entry into meiosis. Although early recombination events were initiated, male germ cells failed to progress beyond zygotene and underwent apoptosis. Loss of APC/CFZR1 activity was associated with raised cyclin B1 levels, suggesting that CDK1 may trigger apoptosis. By contrast, female FZR1? mice were subfertile, with premature onset of ovarian failure by 5 months of age. Germ cell loss occurred embryonically in the ovary, around the time of the zygotene-pachytene transition, similar to that observed in males. In addition, the transition of primordial follicles into the growing follicle pool in the neonatal ovary was abnormal, such that the primordial follicles were prematurely depleted. We conclude that APC/CFZR1 is an essential regulator of spermatogonial proliferation and early meiotic prophase I in both male and female germ cells and is therefore important in establishing the reproductive health of adult male and female mammals.

fzr1, mouse, meiosis, spermatogenesis, oogenesis, apc/c, cdh1
1477-9129
1354-1365
Holt, J.E.
a5879a86-a0c3-4c6e-87cc-54a65d97f0d8
Pye, V.
6b5fa125-b6e8-4d01-9b1d-ec6e50f56d86
Boon, E.
7e9dca09-09f1-4e84-a879-c85ebe7f2a3f
Stewart, J.L.
bfe227e0-4f0f-42a3-b224-9ac0d23b4b5a
Garcia-Higuera, I.
ab01b377-1951-41f3-b251-8f6cf260a152
Moreno, S.
1b609bb5-0b9b-460d-bed2-39266662d75f
Rodriguez, R.
7ba4d3ae-a71a-4e93-af30-34592ca72163
Jones, K.T.
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
McLaughlin, E.A.
7c56b7a6-5c2c-47db-8206-d96ee3630c64
Holt, J.E.
a5879a86-a0c3-4c6e-87cc-54a65d97f0d8
Pye, V.
6b5fa125-b6e8-4d01-9b1d-ec6e50f56d86
Boon, E.
7e9dca09-09f1-4e84-a879-c85ebe7f2a3f
Stewart, J.L.
bfe227e0-4f0f-42a3-b224-9ac0d23b4b5a
Garcia-Higuera, I.
ab01b377-1951-41f3-b251-8f6cf260a152
Moreno, S.
1b609bb5-0b9b-460d-bed2-39266662d75f
Rodriguez, R.
7ba4d3ae-a71a-4e93-af30-34592ca72163
Jones, K.T.
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
McLaughlin, E.A.
7c56b7a6-5c2c-47db-8206-d96ee3630c64

Holt, J.E., Pye, V., Boon, E., Stewart, J.L., Garcia-Higuera, I., Moreno, S., Rodriguez, R., Jones, K.T. and McLaughlin, E.A. (2014) The APC/C activator FZR1 is essential for meiotic prophase I in mice. Development, 141 (6), 1354-1365. (doi:10.1242/dev.104828).

Record type: Article

Abstract

Fizzy-related 1 (FZR1) is an activator of the Anaphase promoting complex/cyclosome (APC/C) and an important regulator of the mitotic cell division cycle. Using a germ-cell-specific conditional knockout model we examined its role in entry into meiosis and early meiotic events in both sexes. Loss of APC/CFZR1 activity in the male germline led to both a mitotic and a meiotic testicular defect resulting in infertility due to the absence of mature spermatozoa. Spermatogonia in the prepubertal testes of such mice had abnormal proliferation and delayed entry into meiosis. Although early recombination events were initiated, male germ cells failed to progress beyond zygotene and underwent apoptosis. Loss of APC/CFZR1 activity was associated with raised cyclin B1 levels, suggesting that CDK1 may trigger apoptosis. By contrast, female FZR1? mice were subfertile, with premature onset of ovarian failure by 5 months of age. Germ cell loss occurred embryonically in the ovary, around the time of the zygotene-pachytene transition, similar to that observed in males. In addition, the transition of primordial follicles into the growing follicle pool in the neonatal ovary was abnormal, such that the primordial follicles were prematurely depleted. We conclude that APC/CFZR1 is an essential regulator of spermatogonial proliferation and early meiotic prophase I in both male and female germ cells and is therefore important in establishing the reproductive health of adult male and female mammals.

Text
Development-2014-Holt-dev.104828.pdf - Other
Restricted to Registered users only
Download (5MB)
Request a copy

More information

Published date: 2014
Keywords: fzr1, mouse, meiosis, spermatogenesis, oogenesis, apc/c, cdh1
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 363736
URI: http://eprints.soton.ac.uk/id/eprint/363736
ISSN: 1477-9129
PURE UUID: ea9cbf38-5a71-4ad8-a16a-f7fd0ff729f0
ORCID for K.T. Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 01 Apr 2014 15:49
Last modified: 10 Sep 2019 00:36

Export record

Altmetrics

Contributors

Author: J.E. Holt
Author: V. Pye
Author: E. Boon
Author: J.L. Stewart
Author: I. Garcia-Higuera
Author: S. Moreno
Author: R. Rodriguez
Author: K.T. Jones ORCID iD
Author: E.A. McLaughlin

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×