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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

Cyclic formation of OSC, granulosa cells nests, and presence of new and resting primary follicles during midfollicular phase. A) Tunica albuginea (ta) fibroblasts (fb) type OSC precursors with CK immunoexpression (brown). Two cells in mesenchymal-OSCs epithelial transition (fb/osc) are apparent. B) Appearance of OSCs (osc) is associated with CK depletion (-fb). C) Formation of CK+ granulosa cell nests is initiated by a layer of OSC (white arrows) above upper ovarian cortex (uoc). This is overgrown by a developing flap of TA (ta flap or taf in insert) resulting in a bi-layered osc cord (black arrow). Inset shows two layers of the OSC channel. D) Detail of OSC flap with CK+ fibroblast type OSC precursors (fb/osc), and OSC development above the upper ovarian cortex (arched arrow). Arrowhead indicates the flap content of OSCs. E) A parallel section to (D) showing numerous DR+ MDC (asterisks) in the TA flap. Note DR expression in early OSC (arrow). F) Detail of OSC-cord from panel C shows CK+ epithelial cord. G) OSC flap (red arrowhead) over a segment of TA (dashed line) covered by OSC layer (red arrow). The OSC cord-derived granulosa cell clusters (black arrows) fragment into granulosa cell nests (black arrowheads). Dashed line indicates a segment of TA covered by OSC epithelium. H) Granulosa cell nests (black arrowheads) move by stromal rearrangements (arched arrow) to the lower ovarian cortex (loc) and form new primary follicles (white arrowhead) containing ZP+ oocytes. I) Lower ovarian cortex (loc) with new primary (right panel segment) and resting primary follicles (left). Right inset shows the presence of primary Balbiani bodies. Left inset shows lack of Balbiani bodies. Bar in (A), for (A and B), bar in (F) for (D-F). Adapted from Ref. [23]: © Antonin Bukovsky.
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Fig5: Cyclic formation of OSC, granulosa cells nests, and presence of new and resting primary follicles during midfollicular phase. A) Tunica albuginea (ta) fibroblasts (fb) type OSC precursors with CK immunoexpression (brown). Two cells in mesenchymal-OSCs epithelial transition (fb/osc) are apparent. B) Appearance of OSCs (osc) is associated with CK depletion (-fb). C) Formation of CK+ granulosa cell nests is initiated by a layer of OSC (white arrows) above upper ovarian cortex (uoc). This is overgrown by a developing flap of TA (ta flap or taf in insert) resulting in a bi-layered osc cord (black arrow). Inset shows two layers of the OSC channel. D) Detail of OSC flap with CK+ fibroblast type OSC precursors (fb/osc), and OSC development above the upper ovarian cortex (arched arrow). Arrowhead indicates the flap content of OSCs. E) A parallel section to (D) showing numerous DR+ MDC (asterisks) in the TA flap. Note DR expression in early OSC (arrow). F) Detail of OSC-cord from panel C shows CK+ epithelial cord. G) OSC flap (red arrowhead) over a segment of TA (dashed line) covered by OSC layer (red arrow). The OSC cord-derived granulosa cell clusters (black arrows) fragment into granulosa cell nests (black arrowheads). Dashed line indicates a segment of TA covered by OSC epithelium. H) Granulosa cell nests (black arrowheads) move by stromal rearrangements (arched arrow) to the lower ovarian cortex (loc) and form new primary follicles (white arrowhead) containing ZP+ oocytes. I) Lower ovarian cortex (loc) with new primary (right panel segment) and resting primary follicles (left). Right inset shows the presence of primary Balbiani bodies. Left inset shows lack of Balbiani bodies. Bar in (A), for (A and B), bar in (F) for (D-F). Adapted from Ref. [23]: © Antonin Bukovsky.

Mentions: Figure 5 demonstrates formation of fresh OSCs differentiating from the TA CK+ fibroblast-like precursors and cyclic emergence of OSC-derived granulosa cell nests for follicular renewal. CK+ fibroblasts in the TA (OSC precursors formed perinatally from fetal OSCs) and their early transformation into adults OSCs under the ovarian surface are presented. When the epithelial type OSCs are formed, the CK staining in their precursors diminishes.Figure 5


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

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

Cyclic formation of OSC, granulosa cells nests, and presence of new and resting primary follicles during midfollicular phase. A) Tunica albuginea (ta) fibroblasts (fb) type OSC precursors with CK immunoexpression (brown). Two cells in mesenchymal-OSCs epithelial transition (fb/osc) are apparent. B) Appearance of OSCs (osc) is associated with CK depletion (-fb). C) Formation of CK+ granulosa cell nests is initiated by a layer of OSC (white arrows) above upper ovarian cortex (uoc). This is overgrown by a developing flap of TA (ta flap or taf in insert) resulting in a bi-layered osc cord (black arrow). Inset shows two layers of the OSC channel. D) Detail of OSC flap with CK+ fibroblast type OSC precursors (fb/osc), and OSC development above the upper ovarian cortex (arched arrow). Arrowhead indicates the flap content of OSCs. E) A parallel section to (D) showing numerous DR+ MDC (asterisks) in the TA flap. Note DR expression in early OSC (arrow). F) Detail of OSC-cord from panel C shows CK+ epithelial cord. G) OSC flap (red arrowhead) over a segment of TA (dashed line) covered by OSC layer (red arrow). The OSC cord-derived granulosa cell clusters (black arrows) fragment into granulosa cell nests (black arrowheads). Dashed line indicates a segment of TA covered by OSC epithelium. H) Granulosa cell nests (black arrowheads) move by stromal rearrangements (arched arrow) to the lower ovarian cortex (loc) and form new primary follicles (white arrowhead) containing ZP+ oocytes. I) Lower ovarian cortex (loc) with new primary (right panel segment) and resting primary follicles (left). Right inset shows the presence of primary Balbiani bodies. Left inset shows lack of Balbiani bodies. Bar in (A), for (A and B), bar in (F) for (D-F). Adapted from Ref. [23]: © Antonin Bukovsky.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Cyclic formation of OSC, granulosa cells nests, and presence of new and resting primary follicles during midfollicular phase. A) Tunica albuginea (ta) fibroblasts (fb) type OSC precursors with CK immunoexpression (brown). Two cells in mesenchymal-OSCs epithelial transition (fb/osc) are apparent. B) Appearance of OSCs (osc) is associated with CK depletion (-fb). C) Formation of CK+ granulosa cell nests is initiated by a layer of OSC (white arrows) above upper ovarian cortex (uoc). This is overgrown by a developing flap of TA (ta flap or taf in insert) resulting in a bi-layered osc cord (black arrow). Inset shows two layers of the OSC channel. D) Detail of OSC flap with CK+ fibroblast type OSC precursors (fb/osc), and OSC development above the upper ovarian cortex (arched arrow). Arrowhead indicates the flap content of OSCs. E) A parallel section to (D) showing numerous DR+ MDC (asterisks) in the TA flap. Note DR expression in early OSC (arrow). F) Detail of OSC-cord from panel C shows CK+ epithelial cord. G) OSC flap (red arrowhead) over a segment of TA (dashed line) covered by OSC layer (red arrow). The OSC cord-derived granulosa cell clusters (black arrows) fragment into granulosa cell nests (black arrowheads). Dashed line indicates a segment of TA covered by OSC epithelium. H) Granulosa cell nests (black arrowheads) move by stromal rearrangements (arched arrow) to the lower ovarian cortex (loc) and form new primary follicles (white arrowhead) containing ZP+ oocytes. I) Lower ovarian cortex (loc) with new primary (right panel segment) and resting primary follicles (left). Right inset shows the presence of primary Balbiani bodies. Left inset shows lack of Balbiani bodies. Bar in (A), for (A and B), bar in (F) for (D-F). Adapted from Ref. [23]: © Antonin Bukovsky.
Mentions: Figure 5 demonstrates formation of fresh OSCs differentiating from the TA CK+ fibroblast-like precursors and cyclic emergence of OSC-derived granulosa cell nests for follicular renewal. CK+ fibroblasts in the TA (OSC precursors formed perinatally from fetal OSCs) and their early transformation into adults OSCs under the ovarian surface are presented. When the epithelial type OSCs are formed, the CK staining in their precursors diminishes.Figure 5

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