**3.3 Nuclear receptor coregulators in the modulation of progesterone and estrogen signaling in endometriosis**

Endocrinologic literature presents different series of nuclear receptors coregulators,- proteins that intervene to modify chromatin structure and regulate large-scale gene transcription programs by forming large complexes with the nuclear receptors of the target cells [70]. In the female genital tract the *PRG* and *ESR1* are critically regulated by a family of regulatory proteins named steroid receptor coactivators (SRCs) - SRC-1, SRC-2, and SRC-3, the first nuclear receptors coregulators are involved in the balance between E2 and P4 in human endometrium. SRC-1 down regulates P4 target genes in the epithelium, and up regulates them in the stroma; SRC-2 is necessary for human endometrial stromal cells decidualisation [71] for P4 signaling and for ESR1 signaling; the transcriptomic analysis revealed that 50% of SRC-2-regulated genes are also regulated by P4 [72] and it is critical for murine uterine function; ablation of SRC-2 induces partial loss of decidualisation and infertility, and both SRCs ablation induces complete loss of decidualisation [73, 74].
