Müllerian-inhibiting substance function during mammalian sexual development.

Abstract

To investigate the role of Müllerian-inhibiting substance (MIS) in mammalian sexual development, we generated MIS-deficient mice. Although MIS-deficient males had testes that were fully descended and produced functional sperm, they also developed female reproductive organs, which interfered with sperm transfer into females, rendering most of these males infertile. Their testes had Leydig cell hyperplasia and, in one instance, neoplasia. The actions of the two primary hormones of male sexual differentiation were genetically eliminated using the testicular feminization (Tfm) mutation in combination with the MIS mutant allele. XY Tfm/MIS double mutants developed as females, with a uterus, coiled oviducts, and no male reproductive organs except undescended dysfunctional testes. These results suggest that eliminating the presumptive female reproductive tract in male fetuses facilitates fertility and that in testes MIS is a negative regulator of Leydig cell proliferation. Eliminating the presumptive male reproductive tract is necessary for proper oviductal morphogenesis during female mouse development.

• Authors: R R Behringer, M J Finegold, R L Cate
• Journal: Cell (Cell) Vol. 79 Issue 3 Pg. 415-25 (Nov 04 1994) ISSN: 0092-8674 [Print] United States
• PMID: 7954809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycoproteins
• Growth Inhibitors
• Testicular Hormones
• Anti-Mullerian Hormone

Topics

• Androgen-Insensitivity Syndrome (embryology)
• Animals
• Anti-Mullerian Hormone
• Cell Division
• Disorders of Sex Development (genetics, pathology)
• Female
• Fertility (physiology)
• Genitalia, Male (anatomy & histology, embryology)
• Glycoproteins
• Growth Inhibitors (genetics, physiology)
• Leydig Cells (physiology)
• Male
• Mice
• Mice, Knockout
• Morphogenesis
• Mullerian Ducts (embryology)
• Oviducts (growth & development)
• Sex Differentiation (physiology)
• Testicular Hormones (genetics, physiology)
• Testis (pathology)
• Wolffian Ducts (embryology)