Imperial College London
Portrait Picture

ProfessorLesleyRegan

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor
 
 
 
//

Contact

 

+44 (0)20 3312 1798l.regan

 
 
//

Assistant

 

Ms Hazel Blackman +44 (0)20 7594 2104

 
//

Location

 

MWG022Mint WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Salker:2010:10.1371/journal.pone.0010287,
author = {Salker, M and Teklenburg, G and Molokhia, M and Lavery, S and Trew, G and Aojanepong, T and Mardon, HJ and Lokugamage, AU and Rai, R and Landles, C and Roelen, BAJ and Quenby, S and Kuijk, EW and Kavelaars, A and Heijnen, CJ and Regan, L and Macklon, NS and Brosens, JJ},
doi = {10.1371/journal.pone.0010287},
journal = {PLOS One},
title = {Natural Selection of Human Embryos: Impaired Decidualization of Endometrium Disables Embryo-Maternal Interactions and Causes Recurrent Pregnancy Loss},
url = {http://dx.doi.org/10.1371/journal.pone.0010287},
volume = {5},
year = {2010}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Recurrent pregnancy loss (RPL), defined as 3 or more consecutive miscarriages, is widely attributed either torepeated chromosomal instability in the conceptus or to uterine factors that are poorly defined. We tested the hypothesisthat abnormal cyclic differentiation of endometrial stromal cells (ESCs) into specialized decidual cells predisposes to RPL,based on the observation that this process may not only be indispensable for placenta formation in pregnancy but also forembryo recognition and selection at time of implantation.Methodology/Principal Findings: Analysis of mid-secretory endometrial biopsies demonstrated that RPL is associated withdecreased expression of the decidual marker prolactin (PRL) but increased levels of prokineticin-1 (PROK1), a cytokine thatpromotes implantation. These in vivo findings were entirely recapitulated when ESCs were purified from patients with andwithout a history of RPL and decidualized in culture. In addition to attenuated PRL production and prolonged and enhancedPROK1 expression, RPL was further associated with a complete dysregulation of both markers upon treatment of ESCcultures with human chorionic gonadotropin, a glycoprotein hormone abundantly expressed by the implanting embryo. Wepostulated that impaired embryo recognition and selection would clinically be associated with increased fecundity, definedby short time-to-pregnancy (TTP) intervals. Woman-based analysis of the mean and mode TTP in a cohort of 560 RPLpatients showed that 40% can be considered ‘‘superfertile’’, defined by a mean TTP of 3 months or less.Conclusions: Impaired cyclic decidualization of the endometrium facilitates implantation yet predisposes to subsequentpregnancy failure by disabling natural embryo selection and by disrupting the maternal responses to embryonic signals.These findings suggest a novel pathological pathway that unifies maternal and embryonic causes of RPL.
AU  - Salker,M
AU  - Teklenburg,G
AU  - Molokhia,M
AU  - Lavery,S
AU  - Trew,G
AU  - Aojanepong,T
AU  - Mardon,HJ
AU  - Lokugamage,AU
AU  - Rai,R
AU  - Landles,C
AU  - Roelen,BAJ
AU  - Quenby,S
AU  - Kuijk,EW
AU  - Kavelaars,A
AU  - Heijnen,CJ
AU  - Regan,L
AU  - Macklon,NS
AU  - Brosens,JJ
DO  - 10.1371/journal.pone.0010287
PY  - 2010///
SN  - 1932-6203
TI  - Natural Selection of Human Embryos: Impaired Decidualization of Endometrium Disables Embryo-Maternal Interactions and Causes Recurrent Pregnancy Loss
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0010287
UR  - http://hdl.handle.net/10044/1/27685
VL  - 5
ER  -
Download