Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.

Abstract

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6d/d mice revert to their normal expression in Mig-6d/dErbb2d/d mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.

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10.1038/s41467-022-28608-x

Publication Info

Yoo, Jung-Yoon, Tae Hoon Kim, Jung-Ho Shin, Ryan M Marquardt, Ulrich Müller, Asgerally T Fazleabas, Steven L Young, Bruce A Lessey, et al. (2022). Loss of MIG-6 results in endometrial progesterone resistance via ERBB2. Nature communications, 13(1). p. 1101. 10.1038/s41467-022-28608-x Retrieved from https://hdl.handle.net/10161/29060.

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Young

Steven L Young

Professor of Obstetrics and Gynecology

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