SMAD6 inhibits granulosa cell proliferation and follicle growth rate in carrier and noncarrier heifers of the Trio allele

in Reproduction
Authors:
Rafael R DominguesDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA
Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, USA

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https://orcid.org/0000-0002-1407-2617
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Fabiana S AndradeDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA
Departamento de Reprodução e Avaliação Animal, Universidade Federal Rural do Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil

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Joao Paulo N AndradeDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA
Departamento de Reprodução e Avaliação Animal, Universidade Federal Rural do Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil

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Sadrollah M MoghbeliDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA

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Victor Gomez-LeonDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA
Current address: Department of Animal Sciences and Industry, Kansas State University, Manhattan, Kansas, USA

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Guilherme MadureiraDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA

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Marco R B MelloDepartamento de Reprodução e Avaliação Animal, Universidade Federal Rural do Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil

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Brian W KirkpatrickDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA

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Milo C WiltbankDepartment of Animal and Dairy Sciences, University of Wisconsin-Madison, USA
Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, USA

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Correspondence should be addressed to M C Wiltbank; Email: wiltbank@wisc.edu

*(R R Domingues and F S Andrade contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-22-0232
Volume/Issue:
Volume 165: Issue 3
Page Range:
269–279
Article Type:
Research Article
Online Publication Date:
18 Jan 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access

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In brief

Follicle selection is a key event in monovular species. In this manuscript, we demonstrate the role of SMAD6 in promoting decreased granulosa cell proliferation and follicle growth rate in carriers vs noncarriers of the Trio allele and after vs before follicle deviation.

Abstract

Cattle are generally considered a monovular species; however, recently, a bovine high fecundity allele, termed the Trio allele, was discovered. Carriers of Trio have an elevated ovulation rate (3–5), while half-sibling noncarriers are monovular. Carriers of the Trio allele have overexpression in granulosa cells of SMAD6, an inhibitor of oocyte-derived regulators of granulosa cell proliferation and differentiation. In experiment 1, follicle size was tracked for each follicle during a follicular wave. Follicle growth rate was greater before vs after follicle deviation in both carriers and noncarriers. Additionally, follicle growth rate was consistently less in carriers vs noncarriers. In experiment 2, we collected granulosa cells from follicles before and after deviation for evaluation of granulosa cell gene expression. Granulosa cell proliferation was less in carriers vs noncarriers and after vs before follicle deviation (decreased expression of cell cycle genes CCNB1 and CCNA2). The decreased granulosa cell proliferation in noncarriers after deviation was associated with increased SMAD6 expression. Similarly, in experiment 3, decreased expression of SMAD6 in granulosa cells of noncarriers cultured in vitro for 60 h was associated with increased expression of cell cycle genes. This suggests that SMAD6 may not just be inhibiting follicle growth rate in carriers of Trio but may also play a role in the decreased follicle growth after deviation in noncarriers. The hypotheses were supported that (1) follicle growth and granulosa cell proliferation decrease after deviation in both carriers and noncarriers and that (2) granulosa cell proliferation is reduced in carriers compared to noncarriers.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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