Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea

A. Bukovsky, Michael Caudle, Jeffrey Keenan, J. Wimalasena, J. S. Foster, Stuart Van Meter

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morphoregulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary. Out data show that enhanced pRb expression accompanies initiation of oocyte growth and differentiation of granulosa and theca cells, and that low levels of pRb accompany advanced differentiation of these cells. Differentiation of preantral and antral follicles is accompanied by release of Thy-1 differentiation protein from vascular pericytes and association of macrophages with differentiating cells.

Original languageEnglish (US)
Pages (from-to)776-792
Number of pages17
JournalBiology of Reproduction
Volume52
Issue number4
DOIs
StatePublished - Mar 27 1995

Fingerprint

Follicular Atresia
Retinoblastoma Protein
Granulosa Cells
Corpus Luteum
Cell Cycle
Macrophages
Oocytes
Theca Cells
Proteins
Cell Differentiation
Pericytes
Follicular Phase
Growth
Basement Membrane
Blood Vessels
Ovary
Luteal Cells
Antral
Immunohistochemistry
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology

Cite this

@article{54906b8036844c27af71a4639633a832,
title = "Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea",
abstract = "Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morphoregulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary. Out data show that enhanced pRb expression accompanies initiation of oocyte growth and differentiation of granulosa and theca cells, and that low levels of pRb accompany advanced differentiation of these cells. Differentiation of preantral and antral follicles is accompanied by release of Thy-1 differentiation protein from vascular pericytes and association of macrophages with differentiating cells.",
author = "A. Bukovsky and Michael Caudle and Jeffrey Keenan and J. Wimalasena and Foster, {J. S.} and {Van Meter}, Stuart",
year = "1995",
month = "3",
day = "27",
doi = "10.1095/biolreprod52.4.776",
language = "English (US)",
volume = "52",
pages = "776--792",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "4",

}

TY - JOUR

T1 - Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea

AU - Bukovsky, A.

AU - Caudle, Michael

AU - Keenan, Jeffrey

AU - Wimalasena, J.

AU - Foster, J. S.

AU - Van Meter, Stuart

PY - 1995/3/27

Y1 - 1995/3/27

N2 - Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morphoregulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary. Out data show that enhanced pRb expression accompanies initiation of oocyte growth and differentiation of granulosa and theca cells, and that low levels of pRb accompany advanced differentiation of these cells. Differentiation of preantral and antral follicles is accompanied by release of Thy-1 differentiation protein from vascular pericytes and association of macrophages with differentiating cells.

AB - Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morphoregulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary. Out data show that enhanced pRb expression accompanies initiation of oocyte growth and differentiation of granulosa and theca cells, and that low levels of pRb accompany advanced differentiation of these cells. Differentiation of preantral and antral follicles is accompanied by release of Thy-1 differentiation protein from vascular pericytes and association of macrophages with differentiating cells.

UR - http://www.scopus.com/inward/record.url?scp=0028932807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028932807&partnerID=8YFLogxK

U2 - 10.1095/biolreprod52.4.776

DO - 10.1095/biolreprod52.4.776

M3 - Article

VL - 52

SP - 776

EP - 792

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 4

ER -