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Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

Bukovsky A - Reprod. Biol. Endocrinol. (2015)

Bottom Line: Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells.If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions.Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. a_buko@comcast.net.

ABSTRACT
In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

No MeSH data available.


Related in: MedlinePlus

ZP3 expression by OLCs in IVM treated OSC cultures is stolen by fibroblasts.A) OLCs in untreated OSC cultures show week nuclear ZP3 expression, which is absent in accompanying satellite cells (SC) and fibroblasts (FB). Arrowheads indicate tube like ring canals between OLC and SC. Arrows indicate bindings of FBs to the OLC. B) After hCG treatment the OLC exhibits strong nuclear and surface (black arrowhead) ZP3 expression, which is also present in accompanying SC (white arrowhead). The ZP3 expression is stolen by FBs (red arrowheads), leaving the surface of OLC ZP3 depleted (open arrowhead). C) The OSC culture from a 30 years old POF female was IVM (FSH+hCG) pretreated and fertilized with the husband's sperm. The phase contrast (PhC) image from a live culture shows that virtually all sperm are associated with fibroblasts instead with OLCs.
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Fig9: ZP3 expression by OLCs in IVM treated OSC cultures is stolen by fibroblasts.A) OLCs in untreated OSC cultures show week nuclear ZP3 expression, which is absent in accompanying satellite cells (SC) and fibroblasts (FB). Arrowheads indicate tube like ring canals between OLC and SC. Arrows indicate bindings of FBs to the OLC. B) After hCG treatment the OLC exhibits strong nuclear and surface (black arrowhead) ZP3 expression, which is also present in accompanying SC (white arrowhead). The ZP3 expression is stolen by FBs (red arrowheads), leaving the surface of OLC ZP3 depleted (open arrowhead). C) The OSC culture from a 30 years old POF female was IVM (FSH+hCG) pretreated and fertilized with the husband's sperm. The phase contrast (PhC) image from a live culture shows that virtually all sperm are associated with fibroblasts instead with OLCs.

Mentions: Zona pellucida glycoprotein 3 (ZP3) has been recently shown to act as a primary sperm receptor for sperm-egg binding in humans [50]. Figure 9 shows a weak nuclear ZP3 expression, indicating a preparation for cytoplasmic ZP3 synthesis, and no ZP3 expression in associated satellite cell and fibroblasts in untreated OSC culture from a 50 year old human female (F50). The treatment of another F50 culture with hCG caused marked nuclear and surface ZP3 expression in OLC and regressing satellite cell. The accompanying fibroblasts, however, steal the OLC and satellite cell organelles, including ZP3 protein. It is also shown that in FSH & hCG treated OSC culture from POF women in the former clinical trial (see Ref. [26]) the sperm curiously associated with fibroblasts, but not with the OLCs. This suggests that in gonadotropin treated OSC cultures the fibroblasts but not OLCs express the ZP3 glycoprotein.Figure 9


Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

Bukovsky A - Reprod. Biol. Endocrinol. (2015)

ZP3 expression by OLCs in IVM treated OSC cultures is stolen by fibroblasts.A) OLCs in untreated OSC cultures show week nuclear ZP3 expression, which is absent in accompanying satellite cells (SC) and fibroblasts (FB). Arrowheads indicate tube like ring canals between OLC and SC. Arrows indicate bindings of FBs to the OLC. B) After hCG treatment the OLC exhibits strong nuclear and surface (black arrowhead) ZP3 expression, which is also present in accompanying SC (white arrowhead). The ZP3 expression is stolen by FBs (red arrowheads), leaving the surface of OLC ZP3 depleted (open arrowhead). C) The OSC culture from a 30 years old POF female was IVM (FSH+hCG) pretreated and fertilized with the husband's sperm. The phase contrast (PhC) image from a live culture shows that virtually all sperm are associated with fibroblasts instead with OLCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4414002&req=5

Fig9: ZP3 expression by OLCs in IVM treated OSC cultures is stolen by fibroblasts.A) OLCs in untreated OSC cultures show week nuclear ZP3 expression, which is absent in accompanying satellite cells (SC) and fibroblasts (FB). Arrowheads indicate tube like ring canals between OLC and SC. Arrows indicate bindings of FBs to the OLC. B) After hCG treatment the OLC exhibits strong nuclear and surface (black arrowhead) ZP3 expression, which is also present in accompanying SC (white arrowhead). The ZP3 expression is stolen by FBs (red arrowheads), leaving the surface of OLC ZP3 depleted (open arrowhead). C) The OSC culture from a 30 years old POF female was IVM (FSH+hCG) pretreated and fertilized with the husband's sperm. The phase contrast (PhC) image from a live culture shows that virtually all sperm are associated with fibroblasts instead with OLCs.
Mentions: Zona pellucida glycoprotein 3 (ZP3) has been recently shown to act as a primary sperm receptor for sperm-egg binding in humans [50]. Figure 9 shows a weak nuclear ZP3 expression, indicating a preparation for cytoplasmic ZP3 synthesis, and no ZP3 expression in associated satellite cell and fibroblasts in untreated OSC culture from a 50 year old human female (F50). The treatment of another F50 culture with hCG caused marked nuclear and surface ZP3 expression in OLC and regressing satellite cell. The accompanying fibroblasts, however, steal the OLC and satellite cell organelles, including ZP3 protein. It is also shown that in FSH & hCG treated OSC culture from POF women in the former clinical trial (see Ref. [26]) the sperm curiously associated with fibroblasts, but not with the OLCs. This suggests that in gonadotropin treated OSC cultures the fibroblasts but not OLCs express the ZP3 glycoprotein.Figure 9

Bottom Line: Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells.If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions.Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. a_buko@comcast.net.

ABSTRACT
In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

No MeSH data available.


Related in: MedlinePlus