scholarly journals Cellular proliferation and vascularization in ovine fetal ovaries: effects of undernutrition and selenium in maternal diet

Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 699-707 ◽  
Author(s):  
Anna T Grazul-Bilska ◽  
Joel S Caton ◽  
Wendy Arndt ◽  
Kelly Burchill ◽  
Clayton Thorson ◽  
...  

Sheep were fed a maintenance (M) diet with adequate (A) Se or high (H) Se concentration from 21 days before breeding to day 135 of pregnancy. From day 50 to day 135 of pregnancy (tissue collection day), a portion of the ewes from ASe and HSe groups were fed restricted (R; 60% of M) diet. Fetal ovarian sections were stained for: 1) the presence of proliferating cell nuclear antigen (a marker of proliferating cells) to determine the proportion of proliferating primordial follicles, or the labeling index (LI; percentage of proliferating cells) for primordial, primary, secondary and antral follicles, stromal tissues, and blood vessels; 2) factor VIII (a marker of endothelial cells) or 3) a presence of apoptotic cells/bodies. The number of proliferating primordial follicles and the LI of primordial follicles was decreased by R and/or HSe diets. The LI was similar for theca and granulosa cells, and for secondary or antral follicles, but was greater in secondary and antral than in primordial and primary follicles. R diet and/or Se affected the LI in all follicle types, in stromal tissues and blood vessels. A dense network of blood vessels was detected in the areas containing secondary to antral follicles, medulla, and hilus, but areas containing primordial follicles were poorly vascularized. The number of apoptotic cells was minimal. These results demonstrate that nutrient restriction and/or Se level in the maternal diet affected cellular proliferation in follicles, blood vessels, and stromal tissues in fetal ovaries. Thus, plane of nutrition and Se in the maternal diet may impact fetal ovarian development and function.

2006 ◽  
Vol 18 (2) ◽  
pp. 224
Author(s):  
W. J. Arndt ◽  
A. Grazul-Bilska ◽  
J. S. Caton ◽  
E. Borowczyk ◽  
P. P. Borowicz ◽  
...  

Hypertrophy and hyperplasia are the major processes for tissue growth and development. The fetal ovaries represent a type of tissue that expresses high cellular proliferation rates. Selenium (Se) is a mineral that has diverse biological functions and affects cellular proliferation in numerous tissues including cancer, digestive tract, and placenta. It has been demonstrated that levels and sources (organic vs. inorganic) of Se may affect tissue growth. This experiment was designed to determine whether maternal consumption of differing levels of energy and Se impacts cell proliferation in fetal ovarian follicles. Sheep (n = 36) were fed a maintenance (M; 2.12 Mcal/kg) or energy restricted (ER; 60% of maintenance; nutrition restriction occurred from Day 50 to Day 135 of pregnancy) diet with high Se (HSe; 81.5 �g/kg body weight) or normal Se (NSe; 7.4 �g/kg body weight) concentration from 21 days before breeding to Day 135 of pregnancy. At slaughter on Day 135 of pregnancy, fetal tissues were collected and fixed in Carnoy's solution. Ovaries (n = 3-6/treatment group) were weighed, sectioned (one section along the longitudal axis/ovary) and stained for the presence of proliferating cell nuclear antigen (PCNA), a marker for proliferating cells. To determine the proportion of proliferating primordial follicles or the labeling index (percentage of proliferating cells; Jablonka-Shariff et al. 1994 Biol. Reprod. 51, 531) for primary, secondary, and antral follicles, digital images of the tissues were taken and analyzed using a computerized image analysis program (Image-Pro Plus; Media Cybernetics, Inc., Silver Spring, MD, USA). The primordial follicle was considered as proliferating when at least one granulosa cell was PCNA-positive. The number of proliferating and non-proliferating cells was determined for granulosa of primary follicles (n = 225 total) and for granulosa and theca cells of secondary (n = 198) and antral (n = 96) follicles, and used to calculate the labeling index. The data were analyzed using the general linear models procedure of SAS (SAS Institute, Inc., Cary, NC, USA). The number of proliferating primordial follicles was decreased (P < 0.05) by restricted energy diet and Se treatment (11.9 � 1.7 for NSe-M diet vs. 7.2 � 1.3 for HSe-M diet and 8.3 � 0.8 for NSe-ER diet vs. 4.7 � 0.8 for HSe-ER diet). However, energy restriction or Se did not affect labeling index in primary, secondary, and antral follicles. The labeling index was similar for theca and granulosa cells from secondary, or antral follicles. The labeling index was greatest (P < 0.05) for antral, less for secondary and least for primary follicles (24.2 � 1.1% vs. 20.2 � 0.7% vs. 13.3 � 0.4%). These results demonstrate that both level of energy and Se in the maternal diet affects cellular proliferation in primordial but not in primary, secondary, or antral follicles in fetal ovaries. In addition, cellular proliferation increases as fetal follicular development progresses. These data indicate that level of energy and Se in the maternal diet may impact fetal ovarian development during the early stage of folliculogenesis. This work ws supported by USDA grant 2005-35206-15281 and Hatch Project ND01712.


Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 226-233 ◽  
Author(s):  
H.J. Heidebrecht ◽  
F. Buck ◽  
J. Steinmann ◽  
R. Sprenger ◽  
H.H. Wacker ◽  
...  

By immunization with nuclear lysates of L428 cells, we raised a monoclonal mouse antibody, Ki-S2 (IgG1 ). In Western blots, this antibody recognizes a nuclear antigen with an apparent molecular mass of 100 kD, termed p100. Protein sequencing of p100 showed that this is a hitherto unknown protein. Immunohistochemical examination of cryostat and paraffin sections of nearly all human tissue types and neoplasms showed that p100 was exclusively expressed in the nuclei of a fraction of proliferating cells. Cell sorting and fluorescence-activated cell sorting analysis of stimulated peripheral blood mononuclear cells showed that p100 was exclusively expressed in proliferating cells from the transition G1/S until the end of cytokinesis. During mitosis, this protein is strictly associated with the spindle pole and with the mitotic spindle, whereas during S and G2 , p100 is diffusely distributed throughout the cell nucleus. Immediately after completion of cytokinesis, p100 was rapidly degraded. In L428 cells, p100 is phosphorylated at least during mitosis. It has a turnover time of about 1 hour. Studies on routinely processed paraffin sections of specimens of malignant lymphoma, benign and malignant nevocellular tumors, and breast cancer showed that in all cases less than 40% of the Ki-67–positive growth fraction expressed p100. Thus, p100 might prove to be a more reliable measure of cellular proliferation and one that is more closely correlated to cancer prognosis, beyond its general biologic relevance as a cell cycle protein.


1994 ◽  
Vol 6 (4) ◽  
pp. 453-457 ◽  
Author(s):  
Alain Pierre Théon ◽  
Loretta Metzger ◽  
Stephen Griffey

Cell proliferation in canine, feline, and equine tumors was evaluated using immunohistochemical detection of in vitro 5–bromodeoxyuridine (BrdU) incorporation, proliferating cell nuclear antigen (PCNA), and interchromatin-associated antigen (p105). Ten tumors in each species were analyzed. The tumor proliferative fraction (PF) was defined as the percentage of labeled nuclei for 5,000 tumor nuclei counted. Immunoreactivity was observed with all techniques in all species. A good correlation was observed between the proliferative fractions measured with the BrdU (PFBrdU) and PCNA (PFPCNA) techniques ( rs = 0.523, P = 0.0026). There was no correlation between the PFs measured with the BrdU (PFBrdU) and p105 (PFP105) techniques. Using the median values obtained from the different approaches as cutoff points to define slowly and rapidly proliferating tumors, there was an 80% agreement ( P = 0.009) between PFBrdU and PFPCNA and no agreement between PFBrdU and PFP105 The results of this study indicate that both BrdU and PCNA labeling methods can be used reliably for identifying proliferating cells in animal tumors. In addition, PCNA could be used to replace the BrdU method to assess tumor proliferative fraction because it does not require pretreatment of tissues.


Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 226-233 ◽  
Author(s):  
H.J. Heidebrecht ◽  
F. Buck ◽  
J. Steinmann ◽  
R. Sprenger ◽  
H.H. Wacker ◽  
...  

Abstract By immunization with nuclear lysates of L428 cells, we raised a monoclonal mouse antibody, Ki-S2 (IgG1 ). In Western blots, this antibody recognizes a nuclear antigen with an apparent molecular mass of 100 kD, termed p100. Protein sequencing of p100 showed that this is a hitherto unknown protein. Immunohistochemical examination of cryostat and paraffin sections of nearly all human tissue types and neoplasms showed that p100 was exclusively expressed in the nuclei of a fraction of proliferating cells. Cell sorting and fluorescence-activated cell sorting analysis of stimulated peripheral blood mononuclear cells showed that p100 was exclusively expressed in proliferating cells from the transition G1/S until the end of cytokinesis. During mitosis, this protein is strictly associated with the spindle pole and with the mitotic spindle, whereas during S and G2 , p100 is diffusely distributed throughout the cell nucleus. Immediately after completion of cytokinesis, p100 was rapidly degraded. In L428 cells, p100 is phosphorylated at least during mitosis. It has a turnover time of about 1 hour. Studies on routinely processed paraffin sections of specimens of malignant lymphoma, benign and malignant nevocellular tumors, and breast cancer showed that in all cases less than 40% of the Ki-67–positive growth fraction expressed p100. Thus, p100 might prove to be a more reliable measure of cellular proliferation and one that is more closely correlated to cancer prognosis, beyond its general biologic relevance as a cell cycle protein.


2020 ◽  
Vol 29 ◽  
pp. 096368972091830 ◽  
Author(s):  
Ping Zhou ◽  
Andrew Irving ◽  
Huifang Wu ◽  
Juan Luo ◽  
Johana Aguirre ◽  
...  

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.


Author(s):  
А. Г. Гунин ◽  
Н. Н. Голубцова ◽  
Н. К. Корнилова

Целью работы стало исследование содержания белка теплового шока 90 ( HSP 90) в фибробластах дермы человека от эмбрионального развития и до глубокой старости (от 20 нед беременности до 85 лет), а также определение значения HSP 90 для возрастных изменений численности фибробластов в дерме человека. HSP 90, ядерный антиген пролиферирующих клеток ( PCNA ) выявляли в срезах кожи непрямым иммуногистохимическим методом. Результаты показали, что в коже человека от 20 нед беременности до 20 лет доля фибробластов дермы с положительной окраской на HSP 90 остается постоянной. С 21 года до 60 лет наблюдают планомерное уменьшение доли фибробластов дермы, имеющих положительную окраску на HSP 90. У людей 61-85 лет происходит резкое увеличение доли фибробластов дермы с положительной окраской на HSP 90. Возрастные изменения содержания HSP 90 положительных фибробластов в дерме статистически не связаны с возрастным уменьшением общего количества и доли PCNA -положительных фибробластов в дерме. The aim of this work was to examine the content of heat shock protein 90 ( HSP 90) in fibroblasts of human dermis from the development until deep aging (from 20 weeks of pregnancy until 85 years old), and defining of a role of HSP 90 in age-dependent changes in the number of fibroblasts in the dermis. HSP 90, proliferating cells nuclear antigen ( PCNA ) were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for HSP 90 in the dermis is not changed from 20 weeks of development to 20 years old. Percent of HSP 90 positive fibroblasts in dermis is decreased from 21 to 60 years old. From 61 year, the number of HSP 90 positive fibroblasts in dermis is increased. Age-related changes in the number of HSP 90 positive fibroblasts is not statistically associated with an age-related decrease in a total number and percent of PCNA positive fibroblasts the dermis.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 663
Author(s):  
Kwang-Hyun Baek ◽  
Jihye Choi ◽  
Chang-Zhu Pei

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.


2021 ◽  
Author(s):  
Rodolfo Bortolozo Serafim ◽  
Cibele Cardoso ◽  
Vanessa Arfelli ◽  
Valeria Valente ◽  
Leticia Fröhlich Archangelo

Abstract PIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent at the central nervous system. Recent studies have described high levels of PIMREG transcripts in different types of tumors and correlated with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples of glioma patients, assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. We show that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG plays a role in DNA damage response and temozolomide resistance of glioblastoma cells and further support the PIMREG role in tumorigenesis.


1998 ◽  
Vol 24 (3-4) ◽  
pp. 937-941 ◽  
Author(s):  
K. M. Moritz ◽  
A. Butkus ◽  
A. C. Mcfarlane ◽  
A. Albiston ◽  
R. Salenmi ◽  
...  

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