| Summary: | Women with regular cycles having hysterectomy for non-malignant conditions and women undergoing oocyte retrieval for assisted conception were used in the current study. Novel primary cultures and co-cultures of lutinised granulosa cells and fibroblast-like cells allowed the mechanistic <i>in vivo</i> interactions of the corpus luteum to be mimicked with an <i>in vitro</i> system. Herein, activin A is identified as a regulated molecule that may promote tissue remodelling during luteolysis. Activin A is secreted by luteal steroidogenic cells and at physiological concentrations it up regulates MMP-2 activity and expression in luteal fibroblast-like cells. HCG can inhibit activin A through several mechanisms including up regulating activin inhibitors, inhibin A and follistatin. Results suggest that activin is an excellent anti-luteal molecule whose paracrine/endocrine actions are to remove or potentially inhibit luteal tissue formation, and moreover to facilitate human luteolysis. However, the biological actions of activin A are inhibited during maternal recognition of pregnancy in the presence of conceptus-derived hCG which has marked and disparate changes on surrounding cell types that do not expression the hCG receptor. Consequently, luteolysis is presented, such that luteal fibroblast-like MMP-2 is inhibited as hCG-derived cortisol production promotes the maternal recognition of pregnancy.
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