title: Systemic morphine treatment derails normal uterine receptivity, leading to embryo implantation failure in mice.
abstract: Morphine is the oldest worldwide well-known opioid agonist used for pain treatment in clinic, and its illicit use is often associated with adverse pregnancy outcomes in humans. Because of recent dramatic increases in nonmedicinal morphine abuse, one emerging issue is the further revelation of the dark side of illicit opioid uses, particularly in early pregnancy events. In this respect, we have demonstrated that opioid signaling is functionally operative during preimplantation embryo development in mice. However, the pathophysiological significance of the opioid system on uterine functions at peri-implantation remained elusive. In the present study, we demonstrated that opioid receptors were spatiotemporally expressed in the uterus during the peri-implantation period. Employing a pharmacological approach combined with embryo transfer experiments, we further observed that although systemic morphine treatment exerts no apparent adverse influence on preimplantation ovarian secretion of progesterone and estrogen, this aberrant activation of opioid signaling by morphine induces impaired luminal epithelial differentiation, decreased stromal cell proliferation, and poor angiogenesis, and thus hampers uterine receptivity and embryo implantation. These novel findings add a new line of evidence to better understand the causes for obvious adverse effects of opioid abuse on pregnancy success in women.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China University of Chinese Academy of Sciences, Beijing, PR China.
authors: Xiaofang
authors: X
authors: Tang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China University of Chinese Academy of Sciences, Beijing, PR China.
authors: Yongjie
authors: Y
authors: Chen
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
authors: Hao
authors: H
authors: Ran
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
authors: Yufei
authors: Y
authors: Jiang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China University of Chinese Academy of Sciences, Beijing, PR China.
authors: Bo
authors: B
authors: He
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
authors: Bingyan
authors: B
authors: Wang
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China kongshb1313@gmail.com.
authors: Shuangbo
authors: S
authors: Kong
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China hbwang@ioz.ac.cn.
authors: Haibin
authors: H
authors: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes; D011247:Pregnancy; D011555:Pseudopregnancy; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D053978:Pentacyclic Triterpenes; D011957:Receptors, Opioid; D014315:Triterpenes; D009020:Morphine; C050414:celastrol
keywords: angiogenesis; implantation failure; morphine; mouse; uterine receptivity