Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas

Apoptosis is an integral part of the spermatogenic process, necessary to maintain a proper ratio of Sertoli to germ cell numbers and provide an adequate microenvironment to germ cells. Apoptosis may also represent a protective mechanism mediating the elimination of abnormal germ cells. Extensive apo...

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Main Authors: Gurpreet Manku, Martine Culty
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2015-06-01
Series:Asian Journal of Andrology
Subjects:
Online Access:http://ajandrology.com/article.asp?issn=1008-682X;year=2015;volume=17;issue=3;spage=403;epage=414;aulast=Manku
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author Gurpreet Manku
Martine Culty
author_facet Gurpreet Manku
Martine Culty
author_sort Gurpreet Manku
collection DOAJ
description Apoptosis is an integral part of the spermatogenic process, necessary to maintain a proper ratio of Sertoli to germ cell numbers and provide an adequate microenvironment to germ cells. Apoptosis may also represent a protective mechanism mediating the elimination of abnormal germ cells. Extensive apoptosis occurs between the first and second postnatal weeks, at the point when gonocytes, precursors of spermatogonial stem cells, should have migrated toward the basement membrane of the tubules and differentiated into spermatogonia. The mechanisms regulating this process are not well-understood. Gonocytes undergo phases of proliferation, migration, and differentiation which occur in a timely and closely regulated manner. Gonocytes failing to migrate and differentiate properly undergo apoptosis. Inadequate gonocyte differentiation has been suggested to lead to testicular germ cell tumor (TGCT) formation. Here, we examined the expression levels of apoptosis-related genes during gonocyte differentiation by quantitative real-time polymerase chain reaction, identifying 48 pro- and anti-apoptotic genes increased by at least two-fold in rat gonocytes induced to differentiate by retinoic acid, when compared to untreated gonocytes. Further analysis of the most highly expressed genes identified the pro-apoptotic genes Gadd45a and Cycs as upregulated in differentiating gonocytes and in spermatogonia compared with gonocytes. These genes were also significantly downregulated in seminomas, the most common type of TGCT, compared with normal human testicular tissues. These results indicate that apoptosis-related genes are actively regulated during gonocyte differentiation. Moreover, the down-regulation of pro-apoptotic genes in seminomas suggests that they could represent new therapeutic targets in the treatment of TGCTs.
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spelling doaj.art-59bd3812d3434f75980b668746606c152022-12-21T20:20:51ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622015-06-0117340341410.4103/1008-682X.146101Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomasGurpreet MankuMartine CultyApoptosis is an integral part of the spermatogenic process, necessary to maintain a proper ratio of Sertoli to germ cell numbers and provide an adequate microenvironment to germ cells. Apoptosis may also represent a protective mechanism mediating the elimination of abnormal germ cells. Extensive apoptosis occurs between the first and second postnatal weeks, at the point when gonocytes, precursors of spermatogonial stem cells, should have migrated toward the basement membrane of the tubules and differentiated into spermatogonia. The mechanisms regulating this process are not well-understood. Gonocytes undergo phases of proliferation, migration, and differentiation which occur in a timely and closely regulated manner. Gonocytes failing to migrate and differentiate properly undergo apoptosis. Inadequate gonocyte differentiation has been suggested to lead to testicular germ cell tumor (TGCT) formation. Here, we examined the expression levels of apoptosis-related genes during gonocyte differentiation by quantitative real-time polymerase chain reaction, identifying 48 pro- and anti-apoptotic genes increased by at least two-fold in rat gonocytes induced to differentiate by retinoic acid, when compared to untreated gonocytes. Further analysis of the most highly expressed genes identified the pro-apoptotic genes Gadd45a and Cycs as upregulated in differentiating gonocytes and in spermatogonia compared with gonocytes. These genes were also significantly downregulated in seminomas, the most common type of TGCT, compared with normal human testicular tissues. These results indicate that apoptosis-related genes are actively regulated during gonocyte differentiation. Moreover, the down-regulation of pro-apoptotic genes in seminomas suggests that they could represent new therapeutic targets in the treatment of TGCTs.http://ajandrology.com/article.asp?issn=1008-682X;year=2015;volume=17;issue=3;spage=403;epage=414;aulast=Mankuapoptosis; differentiation; gonocytes; seminomas; spermatogonia
spellingShingle Gurpreet Manku
Martine Culty
Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
Asian Journal of Andrology
apoptosis; differentiation; gonocytes; seminomas; spermatogonia
title Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
title_full Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
title_fullStr Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
title_full_unstemmed Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
title_short Dynamic changes in the expression of apoptosis-related genes in differentiating gonocytes and in seminomas
title_sort dynamic changes in the expression of apoptosis related genes in differentiating gonocytes and in seminomas
topic apoptosis; differentiation; gonocytes; seminomas; spermatogonia
url http://ajandrology.com/article.asp?issn=1008-682X;year=2015;volume=17;issue=3;spage=403;epage=414;aulast=Manku
work_keys_str_mv AT gurpreetmanku dynamicchangesintheexpressionofapoptosisrelatedgenesindifferentiatinggonocytesandinseminomas
AT martineculty dynamicchangesintheexpressionofapoptosisrelatedgenesindifferentiatinggonocytesandinseminomas