Regulation of human ovarian folliculogenesis in vitro
Author: Carlsson, Inger Britt
Date: 2008-04-23
Location: B64 Karolinska University Hospital Huddinge
Time: 09.30
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
View/ Open:
thesis.pdf (2.693Mb)
Abstract
Cryopreservation of ovarian tissue containing immature oocytes is one
approach to preserving the potential fertility of young women who risk
losing their oocytes as a consequence of treatment with anti-cancer
agents, or genetic disorders. This cryopreserved tissue can then be
transplanted back into the ovary when the woman wants to have children.
Our research group has also been developing an alternative procedure,
namely maturation of ovarian follicles and their oocytes in vitro, for
cancer patients that risk retransmission of the disease after
transplantation. Live offspring can already be produced in mice from
small antral follicles that have matured and been fertilized in vitro. In
the case of women, it is much more challenging to obtain mature oocytes
from ovarian tissue in vitro, due to the much longer period required for
maturation and the dense structure of this tissue.
Employing ovarian biopsies obtained from volunteers, our research group has been actively optimizing conditions for culturing human ovarian tissue and we have shown that if structural and biochemical systems are kept intact (i.e., by culturing pieces of tissue instead of isolated follicles), primordial human follicles can develop into primary and even secondary follicles in vitro. However, fully mature oocytes have not yet been obtained and further optimization of this system is required. The mechanisms controlling the initiation of the growth of small ovarian follicles are not yet known in detail, although a number of factors produced in the ovary itself are known to be involved. These include the family of transforming growth factor beta, as well as other growth factors.
Our present findings can be summarized as follows: Ovarian cortical tissue should be cultured in the form of cubes on diluted Matrigel matrix and the composition of the extra cellular matrix (ECM) should be chosen on the basis of the goals of the study in question (Article I). Kit ligand (KL) mRNA and c-Kit mRNA and protein are expressed in follicles during all stages of development, from primary to antral stage, and the reduction in the survival of follicles in long-term culture caused by an antibody that blocks the c-Kit receptor indicates that signaling via KL/c-Kit plays an important role in the early development of human ovarian follicles (Article II). Moreover, anti-müllerian hormone (AMH) plays a key role in suppressing the entry of follicles into the growing pool, i.e., is one of the hormones involved in inhibiting the recruitment of primordial follicles (Article III). Finally, endogenous growth differentiation factor-9 (GDF-9) is an important regulator of the transition from primary to secondary follicles; BMPRII-Fc can suppress this transition; and, furthermore, the rhGDF-9 protein promotes the early development and growth of follicles, an effect which could be of clinical value.
Thus, we report here important new information concerning the early maturation of human oocytes and follicles in this culture system. This system provides a valuable tool for the identification of factors that promote or inhibit the recruitment of ovarian follicles and will aid in the improvement of procedures for assisted reproduction.
Employing ovarian biopsies obtained from volunteers, our research group has been actively optimizing conditions for culturing human ovarian tissue and we have shown that if structural and biochemical systems are kept intact (i.e., by culturing pieces of tissue instead of isolated follicles), primordial human follicles can develop into primary and even secondary follicles in vitro. However, fully mature oocytes have not yet been obtained and further optimization of this system is required. The mechanisms controlling the initiation of the growth of small ovarian follicles are not yet known in detail, although a number of factors produced in the ovary itself are known to be involved. These include the family of transforming growth factor beta, as well as other growth factors.
Our present findings can be summarized as follows: Ovarian cortical tissue should be cultured in the form of cubes on diluted Matrigel matrix and the composition of the extra cellular matrix (ECM) should be chosen on the basis of the goals of the study in question (Article I). Kit ligand (KL) mRNA and c-Kit mRNA and protein are expressed in follicles during all stages of development, from primary to antral stage, and the reduction in the survival of follicles in long-term culture caused by an antibody that blocks the c-Kit receptor indicates that signaling via KL/c-Kit plays an important role in the early development of human ovarian follicles (Article II). Moreover, anti-müllerian hormone (AMH) plays a key role in suppressing the entry of follicles into the growing pool, i.e., is one of the hormones involved in inhibiting the recruitment of primordial follicles (Article III). Finally, endogenous growth differentiation factor-9 (GDF-9) is an important regulator of the transition from primary to secondary follicles; BMPRII-Fc can suppress this transition; and, furthermore, the rhGDF-9 protein promotes the early development and growth of follicles, an effect which could be of clinical value.
Thus, we report here important new information concerning the early maturation of human oocytes and follicles in this culture system. This system provides a valuable tool for the identification of factors that promote or inhibit the recruitment of ovarian follicles and will aid in the improvement of procedures for assisted reproduction.
List of papers:
I. Scott JE, Carlsson IB, Bavister BD, Hovatta O (2004). "Human ovarian tissue cultures: extracellular matrix composition, coating density and tissue dimensions." Reprod Biomed Online 9(3): 287-93
Pubmed
II. Carlsson IB, Laitinen MP, Scott JE, Louhio H, Velentzis L, Tuuri T, Aaltonen J, Ritvos O, Winston RM, Hovatta O (2006). "Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture." Reproduction 131(4): 641-9
Pubmed
III. Carlsson IB, Scott JE, Visser JA, Ritvos O, Themmen AP, Hovatta O (2006). "Anti-Müllerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro." Hum Reprod 21(9): 2223-7. Epub 2006 May 23
Pubmed
IV. Carlsson IB, Lindeberg M, Pulkki MM, Pasternack A, Scott JE, Pettersson K, Myllymaa S, Laitinen MPE, Mottershead DG, Ritvos O, Hovatta O (2008). "Effects of Growth differentiation factor-9 agonists and antagonists on early human ovarian follicle growth and survival in long-term culture." JCEM (Submitted)
I. Scott JE, Carlsson IB, Bavister BD, Hovatta O (2004). "Human ovarian tissue cultures: extracellular matrix composition, coating density and tissue dimensions." Reprod Biomed Online 9(3): 287-93
Pubmed
II. Carlsson IB, Laitinen MP, Scott JE, Louhio H, Velentzis L, Tuuri T, Aaltonen J, Ritvos O, Winston RM, Hovatta O (2006). "Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture." Reproduction 131(4): 641-9
Pubmed
III. Carlsson IB, Scott JE, Visser JA, Ritvos O, Themmen AP, Hovatta O (2006). "Anti-Müllerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro." Hum Reprod 21(9): 2223-7. Epub 2006 May 23
Pubmed
IV. Carlsson IB, Lindeberg M, Pulkki MM, Pasternack A, Scott JE, Pettersson K, Myllymaa S, Laitinen MPE, Mottershead DG, Ritvos O, Hovatta O (2008). "Effects of Growth differentiation factor-9 agonists and antagonists on early human ovarian follicle growth and survival in long-term culture." JCEM (Submitted)
Issue date: 2008-04-02
Rights:
Publication year: 2008
ISBN: 978-91-7357-583-6
Statistics
Total Visits
Views | |
---|---|
Regulation ...(legacy) | 912 |
Regulation ... | 256 |
Total Visits Per Month
September 2023 | October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | |
---|---|---|---|---|---|---|---|
Regulation ... | 10 | 21 | 12 | 16 | 14 | 13 | 15 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 1479 |
thesis.pdf | 652 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 378 |
Sweden | 81 |
China | 65 |
United Kingdom | 63 |
Ireland | 60 |
Germany | 58 |
Russia | 21 |
India | 20 |
Belgium | 16 |
South Korea | 16 |
Top cities views
Views | |
---|---|
Dublin | 60 |
Sunnyvale | 48 |
Romeo | 26 |
Beijing | 21 |
Kiez | 19 |
Ghent | 15 |
Seoul | 15 |
Borås | 11 |
Stockholm | 9 |
Ballerup | 8 |