The molecular basis of recurrent pregnancy loss: impaired natural embryo selection
The molecular basis of recurrent pregnancy loss: impaired natural embryo selection
Recurrent pregnancy loss (RPL) is a common and distressing disorder. Chromosomal errors in the embryo are the single most common cause, whereas uterine factors are invariably invoked to explain non-chromosomal miscarriages. These uterine factors are, however, poorly defined. The ability of a conceptus to implant in the endometrium is normally restricted to a few days in the menstrual cycle. A limited ‘window of implantation’ ensures coordinated embryonic and endometrial development, thereby minimizing the risk of late implantation of compromised embryos. In this paper, we review emerging evidence, indicating that RPL is associated with impaired differentiation of endometrial stromal cells into specialized decidual cells. From a functional perspective, this differentiation process, termed decidualization, is not only critical for placental development but also signals the end of the implantation window and bestows on the endometrium the ability to recognize, respond to and eliminate implanting compromised embryos. Thus, we propose that spontaneous decidualization of the human endometrium, which inevitably causes menstrual shedding in the absence of a viable conceptus, serves as functional ‘window for natural embryo selection’. Conversely, impaired decidualization predisposes to late implantation, negates embryo quality control and causes early placental failure, regardless of the embryonic karyotype. This pathological pathway also explains the common observation that many RPL patients seem exceptionally fertile, often conceiving within one or two cycles. Thus, as the clinical correlate of inappropriate uterine receptivity, ‘superfertility’ should be considered as a genuine reproductive disorder that requires targeted intervention.
fertility, miscarriage, endometrium, decidualization, embryo
886-896
Teklenburg, G.
4575b926-790e-4d72-a444-9bd8df4fdca9
Salker, Madhuri
f64ad83e-6d95-4219-9212-e9fe642c079c
Macklon, Nick S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e
Brosens, Jan J.
0644527d-213a-44f8-9557-0588eaaac2c9
December 2010
Teklenburg, G.
4575b926-790e-4d72-a444-9bd8df4fdca9
Salker, Madhuri
f64ad83e-6d95-4219-9212-e9fe642c079c
Macklon, Nick S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e
Brosens, Jan J.
0644527d-213a-44f8-9557-0588eaaac2c9
Teklenburg, G., Salker, Madhuri, Macklon, Nick S. and Brosens, Jan J.
(2010)
The molecular basis of recurrent pregnancy loss: impaired natural embryo selection.
Molecular Human Reproduction, 16 (12), .
(doi:10.1093/molehr/gaq079).
(PMID:20847090)
Abstract
Recurrent pregnancy loss (RPL) is a common and distressing disorder. Chromosomal errors in the embryo are the single most common cause, whereas uterine factors are invariably invoked to explain non-chromosomal miscarriages. These uterine factors are, however, poorly defined. The ability of a conceptus to implant in the endometrium is normally restricted to a few days in the menstrual cycle. A limited ‘window of implantation’ ensures coordinated embryonic and endometrial development, thereby minimizing the risk of late implantation of compromised embryos. In this paper, we review emerging evidence, indicating that RPL is associated with impaired differentiation of endometrial stromal cells into specialized decidual cells. From a functional perspective, this differentiation process, termed decidualization, is not only critical for placental development but also signals the end of the implantation window and bestows on the endometrium the ability to recognize, respond to and eliminate implanting compromised embryos. Thus, we propose that spontaneous decidualization of the human endometrium, which inevitably causes menstrual shedding in the absence of a viable conceptus, serves as functional ‘window for natural embryo selection’. Conversely, impaired decidualization predisposes to late implantation, negates embryo quality control and causes early placental failure, regardless of the embryonic karyotype. This pathological pathway also explains the common observation that many RPL patients seem exceptionally fertile, often conceiving within one or two cycles. Thus, as the clinical correlate of inappropriate uterine receptivity, ‘superfertility’ should be considered as a genuine reproductive disorder that requires targeted intervention.
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Published date: December 2010
Keywords:
fertility, miscarriage, endometrium, decidualization, embryo
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Local EPrints ID: 185253
URI: http://eprints.soton.ac.uk/id/eprint/185253
ISSN: 1360-9947
PURE UUID: b79c936e-808b-4223-812a-51fbb7f49b2e
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Date deposited: 10 May 2011 09:08
Last modified: 14 Mar 2024 03:12
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Contributors
Author:
G. Teklenburg
Author:
Madhuri Salker
Author:
Nick S. Macklon
Author:
Jan J. Brosens
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