Cargando…
Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients
BACKGROUND: Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987946/ https://www.ncbi.nlm.nih.gov/pubmed/20969784 http://dx.doi.org/10.1186/1477-7827-8-126 |
_version_ | 1782192191888687104 |
---|---|
author | Meresman, Gabriela F Olivares, Carla Vighi, Susana Alfie, Margarita Irigoyen, Marcela Etchepareborda, Juan J |
author_facet | Meresman, Gabriela F Olivares, Carla Vighi, Susana Alfie, Margarita Irigoyen, Marcela Etchepareborda, Juan J |
author_sort | Meresman, Gabriela F |
collection | PubMed |
description | BACKGROUND: Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium. METHODS: Thirty-seven endometrial samples from sterile or recurrent abortion patients were included in this study: 21 in-phase samples (controls) and 16 samples with out-of-phase endometrium. Biopsy specimens of eutopic endometrium were obtained from all subjects during days 21-25 of the menstrual cycle. The endometrium with endometrial maturity of cycle day 25 or less at the time of menstruation was considered out-of phase. Endometrial tissues were fixed in 10% buffered formaldehyde. For apoptosis quantification, sections were processed for in situ immunohistochemical localization of nuclei exhibiting DNA fragmentation, by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP digoxygenin nick-end labeling (TUNEL) technique. Expressions of Proliferating Cell Nuclear Antigen (PCNA) as a marker of cell proliferation, and of cleaved caspase-3 as a marker of apoptosis, were assessed by immunohistochemistry in the luteal in-phase and out-of-phase endometrium from infertile and recurrent abortion patients. RESULTS: Luteal out-of-phase endometrium had increased apoptosis levels compared to in-phase endometrium (p < 0.05). Caspase-3 evaluation confirmed these results: the luteal out-of-phase endometrium showed augmented cleaved caspase-3 expression (p < 0.005). As well, our data demonstrated that the luteal out-of-phase endometrium expresses decreased PCNA levels (p < 0.05), showing that cell proliferation is diminished in this tissue. CONCLUSIONS: this study represents the first report describing variations at the cell proliferation and cell death levels in the out-of-phase endometrium in comparison with in-phase endometrium from infertile and recurrent abortion patients. Further studies are needed to elucidate a potential role of these alterations in the physiopathology of luteal phase deficiency. |
format | Text |
id | pubmed-2987946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29879462010-11-19 Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients Meresman, Gabriela F Olivares, Carla Vighi, Susana Alfie, Margarita Irigoyen, Marcela Etchepareborda, Juan J Reprod Biol Endocrinol Research BACKGROUND: Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium. METHODS: Thirty-seven endometrial samples from sterile or recurrent abortion patients were included in this study: 21 in-phase samples (controls) and 16 samples with out-of-phase endometrium. Biopsy specimens of eutopic endometrium were obtained from all subjects during days 21-25 of the menstrual cycle. The endometrium with endometrial maturity of cycle day 25 or less at the time of menstruation was considered out-of phase. Endometrial tissues were fixed in 10% buffered formaldehyde. For apoptosis quantification, sections were processed for in situ immunohistochemical localization of nuclei exhibiting DNA fragmentation, by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP digoxygenin nick-end labeling (TUNEL) technique. Expressions of Proliferating Cell Nuclear Antigen (PCNA) as a marker of cell proliferation, and of cleaved caspase-3 as a marker of apoptosis, were assessed by immunohistochemistry in the luteal in-phase and out-of-phase endometrium from infertile and recurrent abortion patients. RESULTS: Luteal out-of-phase endometrium had increased apoptosis levels compared to in-phase endometrium (p < 0.05). Caspase-3 evaluation confirmed these results: the luteal out-of-phase endometrium showed augmented cleaved caspase-3 expression (p < 0.005). As well, our data demonstrated that the luteal out-of-phase endometrium expresses decreased PCNA levels (p < 0.05), showing that cell proliferation is diminished in this tissue. CONCLUSIONS: this study represents the first report describing variations at the cell proliferation and cell death levels in the out-of-phase endometrium in comparison with in-phase endometrium from infertile and recurrent abortion patients. Further studies are needed to elucidate a potential role of these alterations in the physiopathology of luteal phase deficiency. BioMed Central 2010-10-22 /pmc/articles/PMC2987946/ /pubmed/20969784 http://dx.doi.org/10.1186/1477-7827-8-126 Text en Copyright ©2010 Meresman et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Meresman, Gabriela F Olivares, Carla Vighi, Susana Alfie, Margarita Irigoyen, Marcela Etchepareborda, Juan J Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title | Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title_full | Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title_fullStr | Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title_full_unstemmed | Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title_short | Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
title_sort | apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987946/ https://www.ncbi.nlm.nih.gov/pubmed/20969784 http://dx.doi.org/10.1186/1477-7827-8-126 |
work_keys_str_mv | AT meresmangabrielaf apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients AT olivarescarla apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients AT vighisusana apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients AT alfiemargarita apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients AT irigoyenmarcela apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients AT etcheparebordajuanj apoptosisisincreasedandcellproliferationisdecreasedinoutofphaseendometriafrominfertileandrecurrentabortionpatients |