Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation.
Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimpla...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2858159?pdf=render |
| _version_ | 1811200253373710336 |
|---|---|
| author | Gijs Teklenburg Madhuri Salker Mariam Molokhia Stuart Lavery Geoffrey Trew Tepchongchit Aojanepong Helen J Mardon Amali U Lokugamage Raj Rai Christian Landles Bernard A J Roelen Siobhan Quenby Ewart W Kuijk Annemieke Kavelaars Cobi J Heijnen Lesley Regan Jan J Brosens Nick S Macklon |
| author_facet | Gijs Teklenburg Madhuri Salker Mariam Molokhia Stuart Lavery Geoffrey Trew Tepchongchit Aojanepong Helen J Mardon Amali U Lokugamage Raj Rai Christian Landles Bernard A J Roelen Siobhan Quenby Ewart W Kuijk Annemieke Kavelaars Cobi J Heijnen Lesley Regan Jan J Brosens Nick S Macklon |
| author_sort | Gijs Teklenburg |
| collection | DOAJ |
| description | Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown.We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1beta, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo.Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies. |
| first_indexed | 2024-04-12T02:01:37Z |
| format | Article |
| id | doaj.art-b5367540c86a41c39c1b7169889fd6c0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T02:01:37Z |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b5367540c86a41c39c1b7169889fd6c02022-12-22T03:52:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1025810.1371/journal.pone.0010258Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation.Gijs TeklenburgMadhuri SalkerMariam MolokhiaStuart LaveryGeoffrey TrewTepchongchit AojanepongHelen J MardonAmali U LokugamageRaj RaiChristian LandlesBernard A J RoelenSiobhan QuenbyEwart W KuijkAnnemieke KavelaarsCobi J HeijnenLesley ReganJan J BrosensNick S MacklonPregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown.We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1beta, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo.Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies.http://europepmc.org/articles/PMC2858159?pdf=render |
| spellingShingle | Gijs Teklenburg Madhuri Salker Mariam Molokhia Stuart Lavery Geoffrey Trew Tepchongchit Aojanepong Helen J Mardon Amali U Lokugamage Raj Rai Christian Landles Bernard A J Roelen Siobhan Quenby Ewart W Kuijk Annemieke Kavelaars Cobi J Heijnen Lesley Regan Jan J Brosens Nick S Macklon Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. PLoS ONE |
| title | Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. |
| title_full | Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. |
| title_fullStr | Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. |
| title_full_unstemmed | Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. |
| title_short | Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. |
| title_sort | natural selection of human embryos decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation |
| url | http://europepmc.org/articles/PMC2858159?pdf=render |
| work_keys_str_mv | AT gijsteklenburg naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT madhurisalker naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT mariammolokhia naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT stuartlavery naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT geoffreytrew naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT tepchongchitaojanepong naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT helenjmardon naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT amaliulokugamage naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT rajrai naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT christianlandles naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT bernardajroelen naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT siobhanquenby naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT ewartwkuijk naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT annemiekekavelaars naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT cobijheijnen naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT lesleyregan naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT janjbrosens naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation AT nicksmacklon naturalselectionofhumanembryosdecidualizingendometrialstromalcellsserveassensorsofembryoqualityuponimplantation |