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Article: The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta

TitleThe effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta
Authors
Issue Date2013
PublisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/
Citation
Human Reproduction, 2013, v. 28 n. 11, p. 2912-2199 How to Cite?
AbstractSTUDY QUESTION: What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies? SUMMARY ANSWER: The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy. WHAT IS KNOWN ALREADY: There have been no data in the literature on the effect of letrozole in termination of human pregnancies. STUDY DESIGN, SIZE, DURATION: This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT-PCR analysis of ERα and estrogen receptor-β (ERβ), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERβ, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis. MAIN RESULTS AND THE ROLE OF CHANCE: Real-time RT-PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus 4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07-2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200-286) in the control group, in cytotrophoblasts; P = 0.004], while the expression levels of ERβ, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the two groups. LIMITATIONS, REASONS FOR CAUTION: Only the placentae from the second trimester termination of pregnancy were collected in this study. Information from first trimester terminations is still lacking. WIDER IMPLICATIONS OF THE FINDINGS: The results shed some light on the mechanism of action of letrozole pretreatment in termination of pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the GRF/RGC and CRCG grants of the University of Hong Kong. TRIAL REGISTRATION NUMBER: HKClinicalTrials.com with trial number HKCTR-695.
Persistent Identifierhttp://hdl.handle.net/10722/193618
ISSN
2015 Impact Factor: 4.621
2015 SCImago Journal Rankings: 2.271
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, VCYen_US
dc.contributor.authorGao, Jen_US
dc.contributor.authorLee, CKFen_US
dc.contributor.authorNg, EHYen_US
dc.contributor.authorYeung, WSBen_US
dc.contributor.authorHo, PCen_US
dc.date.accessioned2014-01-20T05:10:01Z-
dc.date.available2014-01-20T05:10:01Z-
dc.date.issued2013en_US
dc.identifier.citationHuman Reproduction, 2013, v. 28 n. 11, p. 2912-2199en_US
dc.identifier.issn0268-1161-
dc.identifier.urihttp://hdl.handle.net/10722/193618-
dc.description.abstractSTUDY QUESTION: What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies? SUMMARY ANSWER: The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy. WHAT IS KNOWN ALREADY: There have been no data in the literature on the effect of letrozole in termination of human pregnancies. STUDY DESIGN, SIZE, DURATION: This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT-PCR analysis of ERα and estrogen receptor-β (ERβ), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERβ, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis. MAIN RESULTS AND THE ROLE OF CHANCE: Real-time RT-PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus 4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07-2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200-286) in the control group, in cytotrophoblasts; P = 0.004], while the expression levels of ERβ, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the two groups. LIMITATIONS, REASONS FOR CAUTION: Only the placentae from the second trimester termination of pregnancy were collected in this study. Information from first trimester terminations is still lacking. WIDER IMPLICATIONS OF THE FINDINGS: The results shed some light on the mechanism of action of letrozole pretreatment in termination of pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the GRF/RGC and CRCG grants of the University of Hong Kong. TRIAL REGISTRATION NUMBER: HKClinicalTrials.com with trial number HKCTR-695.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://humrep.oxfordjournals.org/-
dc.relation.ispartofHuman Reproductionen_US
dc.titleThe effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placentaen_US
dc.typeArticleen_US
dc.identifier.emailLee, VCY: v200lee@hku.hken_US
dc.identifier.emailGao, J: helengj@hku.hken_US
dc.identifier.emailLee, CKF: ckflee@hku.hken_US
dc.identifier.emailNg, EHY: nghye@hku.hken_US
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hken_US
dc.identifier.emailHo, PC: pcho@hku.hken_US
dc.identifier.authorityLee, CKF=rp00458en_US
dc.identifier.authorityNg, EHY=rp00426en_US
dc.identifier.authorityYeung, WSB=rp00331en_US
dc.identifier.authorityHo, PC=rp00325en_US
dc.identifier.doi10.1093/humrep/det345en_US
dc.identifier.pmid23980056-
dc.identifier.scopuseid_2-s2.0-84885937964-
dc.identifier.hkuros227374en_US
dc.identifier.volume28en_US
dc.identifier.issue11en_US
dc.identifier.spage2912en_US
dc.identifier.epage2199en_US
dc.identifier.isiWOS:000325762400005-
dc.publisher.placeUnited Kingdom-

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