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Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a

Nature volume 395, pages 707–710 (1998)Cite this article

Abstract

An important feature of mammalian development is the generation of sexually dimorphic reproductive tracts from the Müllerian and Wolffian ducts. In females, Müllerian ducts develop into the oviduct, uterus, cervix and upper vagina, whereas Wolffian ducts regress. In males, testosterone promotes differentiation of Wolffian ducts into the epididymis, vas deferens and seminal vesicle. The Sertoli cells of the testes produce Müllerian-inhibiting substance, which stimulates Müllerian duct regression in males1,2,3,4. The receptor for Müllerian-inhibiting substance is expressed by mesenchymal cells underlying the Müllerian duct that are thought to mediate regression of the duct5,6,7. Mutations that inactivate either Müllerian-inhibiting substance or its receptor allow development of the female reproductive tract in males8,9,10,11,12. These pseudohermaphrodites are frequently infertile because sperm passage is blocked by the presence of the female reproductive system9,10,12. Here we show that male mice lacking the signalling molecule Wnt-7a fail to undergo regression of the Müllerian duct as a result of the absence of the receptor for Müllerian-inhibiting substance. Wnt7a-deficient females are infertile because of abnormal development of the oviduct and uterus, both of which are Müllerian duct derivatives. Therefore, we propose that signalling by Wnt-7a allows sexually dimorphic development of the Müllerian ducts.

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Figure 1: Development of female reproductive tracts in wild-type and Wnt-7a-mutant mice.
Figure 2: Sections through the reproductive tracts of adult wild-type and Wnt-7a-mutant mice.
Figure 3: Male reproductive tracts in wild-type (a, c, e) and Wnt-7a-mutant (b, d, f) mice.
Figure 4: In situ hybridization was used to analyse Wnt-7a and Müllerian-inhibiting substance (MIS)-receptor messenger RNA expression in the Müllerian duct at 14.5 d.p.c.

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Acknowledgements

We thank B. Klumpar for histology and W. Baarends for the MIS type II receptor probe. This work was supported by a grant from the NIH (to A.P.M.).

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  1. Brian A. Parr

    Present address: MCD Biology, University of Colorado, Campus Box 347, Boulder, Colorado, 80309, USA

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  1. Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, 02138, Massachussets, USA

    Andrew P. McMahon

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Correspondence to Andrew P. McMahon.

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Parr, B., McMahon, A. Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Nature 395, 707–710 (1998). https://doi.org/10.1038/27221

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