Targeted ablation of Wnt4 and Wnt5a in Müllerian duct mesenchyme impedes endometrial gland development and causes partial Müllerian agenesis

Biology of Reproduction
Guillaume St-JeanDerek Boerboom

Abstract

Wnt4 and Wnt5a have well-established roles in the embryonic development of the female reproductive tract, as well as in implantation, decidualization, and ovarian function in adult mice. Although these roles appear to overlap, whether Wnt5a and Wnt4 are functionally redundant in these tissues has not been determined. We addressed this by concomitantly inactivating Wnt4 and Wnt5a in the Müllerian mesenchyme and in ovarian granulosa cells by crossing mice bearing floxed alleles to the Amhr2cre strain. Whereas fertility was reduced by ∼50% in Wnt4flox/flox; Amhr2cre/+ and Wnt5aflox/flox; Amhr2cre/+ females, Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice were either nearly or completely sterile. Loss of fertility was not due to an ovarian defect, as serum ovarian hormone levels, follicle counts, and ovulation rates were comparable to controls. Conversely, the uterus was abnormal in Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice, with thin myometrial and stromal layers, frequent fibrosis and a >90% reduction in numbers of uterine glands, suggesting redundant or additive roles of Wnt4 and Wnt5a in uterine adenogenesis. Loss of fertility in Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice was attributed to defects in decidualization, im...Continue Reading

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Citations

Oct 4, 2020·BMC Genomics·Zahida Yesmin RolyCraig A Smith
Dec 18, 2020·Theriogenology·Seetharam Deepa, Balasubramanian Senthilkumaran
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Laura Santana GonzalezAhmed A Ahmed
May 9, 2021·Endocrinology·Lauren M PitzerMatthew J Sikora
Jun 24, 2021·Disease Models & Mechanisms·Laura Santana GonzálezAhmed Ashour Ahmed

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