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Dysregulation of follicle development in a mouse model of premature ovarian insufficiency

Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model o...

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Autores principales: Grasa, P, Sheikh, S, Krzys, N, Millar, K, Janjua, S, Nawaggi, P, Williams, S A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111581/
https://www.ncbi.nlm.nih.gov/pubmed/27581083
http://dx.doi.org/10.1530/REP-16-0091
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author Grasa, P
Sheikh, S
Krzys, N
Millar, K
Janjua, S
Nawaggi, P
Williams, S A
author_facet Grasa, P
Sheikh, S
Krzys, N
Millar, K
Janjua, S
Nawaggi, P
Williams, S A
author_sort Grasa, P
collection PubMed
description Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3β-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.
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spelling pubmed-51115812016-12-19 Dysregulation of follicle development in a mouse model of premature ovarian insufficiency Grasa, P Sheikh, S Krzys, N Millar, K Janjua, S Nawaggi, P Williams, S A Reproduction Research Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3β-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments. Bioscientifica Ltd 2016-10-11 /pmc/articles/PMC5111581/ /pubmed/27581083 http://dx.doi.org/10.1530/REP-16-0091 Text en © 2016 The authors http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Research
Grasa, P
Sheikh, S
Krzys, N
Millar, K
Janjua, S
Nawaggi, P
Williams, S A
Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title_full Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title_fullStr Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title_full_unstemmed Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title_short Dysregulation of follicle development in a mouse model of premature ovarian insufficiency
title_sort dysregulation of follicle development in a mouse model of premature ovarian insufficiency
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111581/
https://www.ncbi.nlm.nih.gov/pubmed/27581083
http://dx.doi.org/10.1530/REP-16-0091
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