title: P-glycoprotein expression and localization in the rat uterus throughout gestation and labor.
abstract: Uterine tissues contain the efflux transporter P-glycoprotein (P-gp, encoded by Abcb1a/1b gene), but little is known about how it changes through gestation. Our aim was to investigate the expression profile and cellular localization of P-gp in the pregnant, laboring and post-partum (PP) rat uterus. We propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial Abcb1a/1b/P-gp. Samples from bilaterally and unilaterally pregnant rats were collected throughout gestation, during labor, and PP (n=4-6/gestational day). RNA and protein were isolated and subjected to quantitative PCR and immunoblotting; P-gp transcript and protein were localized by in situ hybridization and immunohistochemistry. Expression of Abcb1a/1b gene and membrane P-gp protein in uterine tissue (1) increased throughout gestation, peaked at term (GD19-21) and dropped during labor (GD23L); and (2) was upregulated only in gravid but not in empty horn of unilaterally pregnant rats. (3) The drop of Abcb1a/1b mRNA on GD23 was prevented by artificial maintenance of elevated progesterone (P4) levels in late gestation; (4) injection of the P4 receptor antagonist RU486 on GD19 caused a significant decrease in Abcb1 mRNA levels. (5) In situ hybridization and immunohistochemistry indicated that Abcb1/P-gp is absent from myometrium throughout gestation; (6) was expressed exclusively by uterine microvascular endothelium (at early gestation) and luminal epithelium (at mid and late gestation), but was undetectable during labor. In conclusion, ABC transporter protein P-gp in pregnant uterus is hormonally and mechanically regulated. However, its substrate(s) and precise function in these tissues during pregnancy remains to be determined.
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada Division of Obstetrics and GynecologyNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qi-Tao
authors.initials: QT
authors.lastname: Huang
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada Department of Obstetrics & GynecologyUniversity of Toronto, Toronto, Ontario, Canada shynlova@lunenfeld.ca.
authors.forename: Oksana
authors.initials: O
authors.lastname: Shynlova
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Kibschull
authors.affiliation: Division of Obstetrics and GynecologyNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada Department of Obstetrics & GynecologyUniversity of Toronto, Toronto, Ontario, Canada Department of PhysiologyUniversity of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Matthews
authors.affiliation: Lunenfeld-Tanenbaum Research InstituteMount Sinai Hospital, Toronto, Ontario, Canada Department of Obstetrics & GynecologyUniversity of Toronto, Toronto, Ontario, Canada Department of PhysiologyUniversity of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D007743:Labor, Obstetric / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D049590:Postpartum Period / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C095122:multidrug resistance protein 3