Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female infertility

Jennifer A Hernandez Gifford; Mary E Hunzicker-Dunn; John H Nilson

doi:10.1095/biolreprod.108.072280

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Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female infertility

Journal article

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Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female infertility

Jennifer A Hernandez Gifford, Mary E Hunzicker-Dunn and John H Nilson

Biology of reproduction, Vol.80(6), pp.1282-1292

06/2009

DOI: https://doi.org/10.1095/biolreprod.108.072280

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https://hdl.handle.net/2376/107668

PMID: 19176883

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Abstract

Fallopian Tubes - growth & development

Follicle Stimulating Hormone - metabolism

Receptors, Transforming Growth Factor beta - genetics

Cell Proliferation

Response Elements

Cells, Cultured

Gonadal Steroid Hormones - biosynthesis

Aromatase - metabolism

Mullerian Ducts - growth & development

Mice, Transgenic

Ovary - physiology

beta Catenin - metabolism

Infertility, Female - metabolism

Receptors, Peptide - genetics

beta Catenin - genetics

Integrases

Animals

Receptors, Transforming Growth Factor beta - metabolism

Uterus - growth & development

Recombination, Genetic

Female

Mice

Cyclic AMP - metabolism

Receptors, Peptide - metabolism

Follicle-stimulating hormone (FSH) regulation of aromatase gene expression in vitro requires the transcriptional coactivator beta-catenin. To ascertain the physiological significance of beta-catenin in granulosa cells during folliculogenesis, mice homozygous for floxed alleles of beta-catenin were intercrossed with Amhr2cre mice. Conditional deletion of beta-catenin in 8-wk-old females occurred in derivatives of the Müllerian duct, granulosa cells and, surprisingly, in brain, pituitary, heart, liver, and tail. Female mice deficient for beta-catenin were infertile, despite reaching puberty and ovulating at the expected age, indications of apparently normal ovarian function. In contrast, their oviducts were grossly distended, with fewer but healthy oocytes. In addition, their uteri lacked implantation sites. Together, these two phenotypes could explain the complete loss of fertility. Nevertheless, although the ovary appeared normal, with serum estradiol concentrations in the normal range, there was marked animal-to-animal variation of mRNAs encoding beta-catenin and aromatase. Similarly, inhibin-alpha and luteinizing hormone receptor mRNAs varied considerably in whole ovaries, whereas pituitary Fshb mRNA was significantly reduced. Collectively, these features suggested cyclization recombination (CRE)-mediated recombination of beta-catenin may be unstable in proliferating granulosa cells, and therefore may mask the suspected steroidogenic requirement for beta-catenin. We tested this possibility by transducing primary cultures of granulosa cells from mice homozygous for floxed alleles of beta-catenin with a CRE-expressing adenovirus. Reduction of beta-catenin significantly compromised FSH stimulation of aromatase mRNA and subsequent production of estradiol. Collectively, these data suggest that FSH regulation of steroidogenesis requires beta-catenin, a role that remains hidden when tested through Amhr2cre-mediated recombination in vivo.

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Title: Conditional deletion of beta-catenin mediated by Amhr2cre in mice causes female infertility
Creators: Jennifer A Hernandez Gifford - School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4660, USA
Mary E Hunzicker-Dunn
John H Nilson
Publication Details: Biology of reproduction, Vol.80(6), pp.1282-1292
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: P01 HD021921 / NICHD NIH HHS HD-21921 / NICHD NIH HHS
Identifiers: 99900547695401842
Language: English
Resource Type: Journal article