title: Cigarette smoke increases progesterone receptor and homeobox A10 expression in human endometrium and endometrial cells: a potential role in the decreased prevalence of endometrial pathology in smokers.
abstract: Cigarette smoking has long been tied to a multitude of poor health outcomes; however, in reproductive biology, smoking has shown several unintuitive findings. Smoking is associated with significantly decreased rates of endometriosis and endometrial cancer. Here, we show that treatment with cigarette smoke extract leads to increased mRNA and protein expression of homeobox A10 (HOXA10) and progesterone receptor (PGR) as well as more rapid decidualization of endometrial stromal cells in vitro. In vivo, mice exposed to cigarette smoke similarly showed increased expression of HOXA10 and PGR in the endometrium. Both HOXA10 and PGR drive endometrial differentiation and are suppressed in endometrial tumors and in endometriosis. The increased expression found upon exposure to cigarette smoke may provide a protective effect, mediating the decreased incidence of endometrial disease among smokers. This mechanism contrasts with the accepted paradigm that the effects of smoking on the uterus are secondary to ovarian alterations rather than direct effects on endometrium as demonstrated here.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Jorgensen
authors.forename: Ye
authors.initials: Y
authors.lastname: Gan
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D011980:Receptors, Progesterone; D012906:Smoke; C092119:Hoxa10 protein, mouse