Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35232969.
- Also identified by DOI 10.1038/s41467-022-28608-x and PMC identifier 8888616.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (Pgr<sup>cre/+</sup>Mig-6<sup>f/f</sup>; Mig-6<sup>d/d</sup>). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6<sup>d/d</sup> mice (Mig-6<sup>d/d</sup>Erbb2<sup>d/d</sup> mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6<sup>d/d</sup> mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6<sup>d/d</sup> mice revert to their normal expression in Mig-6<sup>d/d</sup>Erbb2<sup>d/d</sup> 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.
Medical subject headings
- Endometriosis
- Infertility, Female
- Intracellular Signaling Peptides and Proteins
- Erb-b2 Receptor Tyrosine Kinases
- Uterine Diseases