Abstract
BackgroundA large body of research highlights the importance of early-life environmental impact on the health outcome in adulthood. However, whether early-life adversity (ELA) has any impact on the development of endometriosis is completely unclear. In this study, we tested the hypothesis that ELA, as manifested by neonatal separation, can accelerate the progression of endometriosis in mouse through activation of the adrenergic receptor β2 (ADRB2) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions.MethodsEight female Balb/C mice, in late pregnancy, were used used for this study, which later gave birth to 22 female newborn pubs. Eleven additional female Balb/C mice were also used as donors of uterine tissues. The 22 newborn pubs were randomly divided into 2 equal-sized groups, maternal separation (MS) and no separation (NS). Pubs in the MS group were separated from their dams for 3 h/day from postnatal day (PND) 1 to 21, while those in the NS control remained in the home cage with their dams. In adulthood (8-week old), 3 mice in each group were randomly selected to undergo a battery of behavior tests. The remaining 8 mice in each group were induced with endometriosis by intraperitoneal injection of uterine fragments from donor mice. Four weeks after the induction, all mice were sacrificed and their endometriotic lesions were excised for quantification and then prepared for immunohistochemistry analysis.ResultsWe confirmed that MS during infancy resulted in anxiety and depression-like behaviors as previously reported. We also found that in MS mice the lesion weight was increased by over 2 folds and generalized hyperalgesia was also significantly increased as compared with NS mice. Immunostaining analysis demonstrated that MS accelerated the development of endometriosis likely through decreased dopamine receptor D2 (DRD2) expression and activation of the ADRB2/cAMP-response element binding protein (CREB) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions.ConclusionsExposure of female mouse pups to ELA such as MS during their infancy period accelerates the progression of endometriosis, possibly through altered neuronal wiring and hyperactivity of the hypothalamic-pituitary-adrenal axis.
Highlights
Endometriosis, characterized by the ectopic presence and growth of functioning endometrial tissues, is a disease affecting 6–10% of women of reproductive age [1]
maternal separation (MS) promotes the development of endometriosis and exacerbates generalized hyperalgesia in adult mice We found that lesions harvested from the mice in the MS group were conspicuously larger than that from no separation (NS) mice (Fig. 2a), and the total lesion weight was significantly increased as compared with the NS mice (p < 0.007; Fig. 2b)
We have shown that MS promotes the development of endometriosis and exacerbates endometriosis-associated generalized hyperalgesia in adult female mice, likely through decreased dopamine receptor D2 (DRD2) expression and activation of the Adrenergic receptor β2 (ADRB2)/cAMP-response element binding protein (CREB) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions
Summary
Endometriosis, characterized by the ectopic presence and growth of functioning endometrial tissues, is a disease affecting 6–10% of women of reproductive age [1]. It became evident that non-nutritional, early-life adversity (ELA), such as abuse, neglect and traumatic events, can have long-lasting effect and profoundly impact on the health status throughout adult life, likely mediated through epigenetic mechanisms [7, 8]. These poor health outcomes include psychological disorders [9, 10] and several somatic pathologies [11, 12]. We tested the hypothesis that ELA, as manifested by neonatal separation, can accelerate the progression of endometriosis in mouse through activation of the adrenergic receptor β2 (ADRB2) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
