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Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood
Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environme...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632956/ https://www.ncbi.nlm.nih.gov/pubmed/26508737 http://dx.doi.org/10.14814/phy2.12587 |
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author | Muzi-Filho, Humberto Souza, Alessandro M Bezerra, Camila G P Boldrini, Leonardo C Takiya, Christina M Oliveira, Felipe L Nesi, Renata T Valença, Samuel S Silva, Ananssa M S Zapata-Sudo, Gisele Sudo, Roberto T Einicker-Lamas, Marcelo Vieyra, Adalberto Lara, Lucienne S Cunha, Valeria M N |
author_facet | Muzi-Filho, Humberto Souza, Alessandro M Bezerra, Camila G P Boldrini, Leonardo C Takiya, Christina M Oliveira, Felipe L Nesi, Renata T Valença, Samuel S Silva, Ananssa M S Zapata-Sudo, Gisele Sudo, Roberto T Einicker-Lamas, Marcelo Vieyra, Adalberto Lara, Lucienne S Cunha, Valeria M N |
author_sort | Muzi-Filho, Humberto |
collection | PubMed |
description | Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environment to which its luminal content is exposed, we hypothesized that the vas deferens would be a highly sensitive target. The goals were to investigate whether intrauterine malnutrition affects molecular mechanisms related to Ca(2+)- and oxidative stress-modulated processes and causes structural alterations in the adult rat vas deferens that could attenuate fecundity and fertility. Male adult rats malnourished in utero had increased vas deferens weight associated with thickening of the muscular coat, a decrease in the total and haploid germ cells, a marked increase in the immature cells, and a decline in the numbers of pregnant females and total offspring per male rat. The ex vivo response of vas deferens from malnourished rats demonstrated an accentuated decrease in the contractile response to phenylephrine. The vas deferens had a marked decrease in Ca(2+) transport due to the uncoupling of Ca(2+)-stimulated ATP hydrolysis and ATP-driven Ca(2+) flux, and the downregulation of both sarco-endoplasmic reticulum Ca(2+)-ATPase 2 and the coupling factor 12-kDa FK506-binding protein. An increase in protein carbonylation (a marker of oxidative damage) and an imbalance between protein kinases C and A were observed as a legacy of undernutrition in early life. These results provide the structural and molecular basis to explain at least in part how maternal undernutrition affects fecundity and fertility in adult male rats. |
format | Online Article Text |
id | pubmed-4632956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-46329562015-11-09 Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood Muzi-Filho, Humberto Souza, Alessandro M Bezerra, Camila G P Boldrini, Leonardo C Takiya, Christina M Oliveira, Felipe L Nesi, Renata T Valença, Samuel S Silva, Ananssa M S Zapata-Sudo, Gisele Sudo, Roberto T Einicker-Lamas, Marcelo Vieyra, Adalberto Lara, Lucienne S Cunha, Valeria M N Physiol Rep Original Research Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environment to which its luminal content is exposed, we hypothesized that the vas deferens would be a highly sensitive target. The goals were to investigate whether intrauterine malnutrition affects molecular mechanisms related to Ca(2+)- and oxidative stress-modulated processes and causes structural alterations in the adult rat vas deferens that could attenuate fecundity and fertility. Male adult rats malnourished in utero had increased vas deferens weight associated with thickening of the muscular coat, a decrease in the total and haploid germ cells, a marked increase in the immature cells, and a decline in the numbers of pregnant females and total offspring per male rat. The ex vivo response of vas deferens from malnourished rats demonstrated an accentuated decrease in the contractile response to phenylephrine. The vas deferens had a marked decrease in Ca(2+) transport due to the uncoupling of Ca(2+)-stimulated ATP hydrolysis and ATP-driven Ca(2+) flux, and the downregulation of both sarco-endoplasmic reticulum Ca(2+)-ATPase 2 and the coupling factor 12-kDa FK506-binding protein. An increase in protein carbonylation (a marker of oxidative damage) and an imbalance between protein kinases C and A were observed as a legacy of undernutrition in early life. These results provide the structural and molecular basis to explain at least in part how maternal undernutrition affects fecundity and fertility in adult male rats. John Wiley & Sons, Ltd 2015-10-27 /pmc/articles/PMC4632956/ /pubmed/26508737 http://dx.doi.org/10.14814/phy2.12587 Text en © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Muzi-Filho, Humberto Souza, Alessandro M Bezerra, Camila G P Boldrini, Leonardo C Takiya, Christina M Oliveira, Felipe L Nesi, Renata T Valença, Samuel S Silva, Ananssa M S Zapata-Sudo, Gisele Sudo, Roberto T Einicker-Lamas, Marcelo Vieyra, Adalberto Lara, Lucienne S Cunha, Valeria M N Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title | Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title_full | Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title_fullStr | Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title_full_unstemmed | Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title_short | Rats undernourished in utero have altered Ca(2+) signaling and reduced fertility in adulthood |
title_sort | rats undernourished in utero have altered ca(2+) signaling and reduced fertility in adulthood |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632956/ https://www.ncbi.nlm.nih.gov/pubmed/26508737 http://dx.doi.org/10.14814/phy2.12587 |
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