We tested the hypothesis that enriched environment (EE), consisting of enlarged space, and increased physical activity and social interactions, hinders the development of
endometriosis through attenuated
adrenergic signaling, enhanced autophagy, and reduced
leptin levels. Two mouse experiments were performed. In Experiment 1, 40 female Balb/C mice were randomly divided into four equal-sized groups, the SE (standard environment), EE, p-EE (EE instituted after
endometriosis induction), and the d-EE (SE housing but received uterine fragments from EE donors) groups. Housing intervention was initiated 3 weeks before the induction of
endometriosis and continued for 3 weeks after induction. In Experiment 2, 20 female mice were randomly divided into SE and EE groups, and the plasma
leptin levels were measured. We measured lesion weight and hotplate latency and performed Masson trichrome staining as well as immunohistochemistry analysis of β2
adrenergic receptor (ADRB2),
dopamine receptor D2 (DRD2),
vascular endothelial growth factor (
VEGF), and
microtubule-associated protein light chain 3 (LC3). We found that EE reduced the lesion weight by 40.8% as compared with SE mice, but the reduction in p-EE and d-EE mice did not reach statistical significance. EE significantly reduced staining levels of ADRB2 and
VEGF as well as the extent of lesional
fibrosis but increased staining levels of LC3 and DRD2 in lesions as compared with the SE group. EE mice had reduced plasma
leptin levels as compared with SE mice. Thus, EE decelerates the development of
endometriosis and fibrogenesis and improved generalized
hyperalgesia, possibly through increased DRD2 expression but decreased expression of ADRB2 and
VEGF as well as enhanced autophagy and reduced
leptin level.