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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

Follicular renewal in adult human ovary and intravascular degeneration of germ cells unattended with granulosa cells. A) Ovarian vein in the lower ovarian cortex lined by endothelial cells (en) and CK+ granulosa nest wall (gnw). In the vein lumen (vl) the granulosa nest wall extends a granulosa nest arm (gna) capturing the circulating oocyte (co). B) Granulosa nest (gn) during formation of the new primary follicle with captured oocyte. Granulosa cells penetrate the ooplasm (red arrowheads) during the primary Balbiani body (asterisk) formation adjacent to the oocyte nucleus (on). CK+ granulosa nest particles (yellow arrowheads) are already dispersed within the oocyte, which still exhibits oocyte tail (ot) outside of the new primary follicle. C) Growing follicle (dashed line circle), with granulosa cells (grc) and oocyte (o) with ZP expression at the oocyte surface (arrow). D) Degenerating oocyte in a medullary vein from the same ovary as in panel C exhibits a strong cytoplasmic ZP expression. E) Heavily ZP+ degenerating oocyte from 28 year-old fertile woman found in the extra ovarian (uterine ectocervix) vein of a patient with follicular renewal shown in panels 4A and 4B. Panels A and B adapted from Ref. [23] : © Antonin Bukovsky; panels C-E adapted from Ref. [41] , with a permission: © Elsevier/North-Holland Biomedical Press.
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Fig4: Follicular renewal in adult human ovary and intravascular degeneration of germ cells unattended with granulosa cells. A) Ovarian vein in the lower ovarian cortex lined by endothelial cells (en) and CK+ granulosa nest wall (gnw). In the vein lumen (vl) the granulosa nest wall extends a granulosa nest arm (gna) capturing the circulating oocyte (co). B) Granulosa nest (gn) during formation of the new primary follicle with captured oocyte. Granulosa cells penetrate the ooplasm (red arrowheads) during the primary Balbiani body (asterisk) formation adjacent to the oocyte nucleus (on). CK+ granulosa nest particles (yellow arrowheads) are already dispersed within the oocyte, which still exhibits oocyte tail (ot) outside of the new primary follicle. C) Growing follicle (dashed line circle), with granulosa cells (grc) and oocyte (o) with ZP expression at the oocyte surface (arrow). D) Degenerating oocyte in a medullary vein from the same ovary as in panel C exhibits a strong cytoplasmic ZP expression. E) Heavily ZP+ degenerating oocyte from 28 year-old fertile woman found in the extra ovarian (uterine ectocervix) vein of a patient with follicular renewal shown in panels 4A and 4B. Panels A and B adapted from Ref. [23] : © Antonin Bukovsky; panels C-E adapted from Ref. [41] , with a permission: © Elsevier/North-Holland Biomedical Press.

Mentions: Figure 4 shows an oocyte-granulosa cell nest assembly with primary Balbiani body formation in the identical ovary of a 28 year old woman, and the fate of circulating oocytes lacking association with granulosa cells. Granulosa cell nests for follicular renewal are formed during follicular phase of ovarian cycle from the OSCs [24], with assistance of DR+ MDCs [23,24,26]. After the nests reach venules in the lower ovarian cortex, CK+ granulosa nest walls replace vein’s endothelial cells and the granulosa nest arm captures a circulating oocyte from the vascular lumen (Figure 4A).Figure 4


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

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

Follicular renewal in adult human ovary and intravascular degeneration of germ cells unattended with granulosa cells. A) Ovarian vein in the lower ovarian cortex lined by endothelial cells (en) and CK+ granulosa nest wall (gnw). In the vein lumen (vl) the granulosa nest wall extends a granulosa nest arm (gna) capturing the circulating oocyte (co). B) Granulosa nest (gn) during formation of the new primary follicle with captured oocyte. Granulosa cells penetrate the ooplasm (red arrowheads) during the primary Balbiani body (asterisk) formation adjacent to the oocyte nucleus (on). CK+ granulosa nest particles (yellow arrowheads) are already dispersed within the oocyte, which still exhibits oocyte tail (ot) outside of the new primary follicle. C) Growing follicle (dashed line circle), with granulosa cells (grc) and oocyte (o) with ZP expression at the oocyte surface (arrow). D) Degenerating oocyte in a medullary vein from the same ovary as in panel C exhibits a strong cytoplasmic ZP expression. E) Heavily ZP+ degenerating oocyte from 28 year-old fertile woman found in the extra ovarian (uterine ectocervix) vein of a patient with follicular renewal shown in panels 4A and 4B. Panels A and B adapted from Ref. [23] : © Antonin Bukovsky; panels C-E adapted from Ref. [41] , with a permission: © Elsevier/North-Holland Biomedical Press.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Follicular renewal in adult human ovary and intravascular degeneration of germ cells unattended with granulosa cells. A) Ovarian vein in the lower ovarian cortex lined by endothelial cells (en) and CK+ granulosa nest wall (gnw). In the vein lumen (vl) the granulosa nest wall extends a granulosa nest arm (gna) capturing the circulating oocyte (co). B) Granulosa nest (gn) during formation of the new primary follicle with captured oocyte. Granulosa cells penetrate the ooplasm (red arrowheads) during the primary Balbiani body (asterisk) formation adjacent to the oocyte nucleus (on). CK+ granulosa nest particles (yellow arrowheads) are already dispersed within the oocyte, which still exhibits oocyte tail (ot) outside of the new primary follicle. C) Growing follicle (dashed line circle), with granulosa cells (grc) and oocyte (o) with ZP expression at the oocyte surface (arrow). D) Degenerating oocyte in a medullary vein from the same ovary as in panel C exhibits a strong cytoplasmic ZP expression. E) Heavily ZP+ degenerating oocyte from 28 year-old fertile woman found in the extra ovarian (uterine ectocervix) vein of a patient with follicular renewal shown in panels 4A and 4B. Panels A and B adapted from Ref. [23] : © Antonin Bukovsky; panels C-E adapted from Ref. [41] , with a permission: © Elsevier/North-Holland Biomedical Press.
Mentions: Figure 4 shows an oocyte-granulosa cell nest assembly with primary Balbiani body formation in the identical ovary of a 28 year old woman, and the fate of circulating oocytes lacking association with granulosa cells. Granulosa cell nests for follicular renewal are formed during follicular phase of ovarian cycle from the OSCs [24], with assistance of DR+ MDCs [23,24,26]. After the nests reach venules in the lower ovarian cortex, CK+ granulosa nest walls replace vein’s endothelial cells and the granulosa nest arm captures a circulating oocyte from the vascular lumen (Figure 4A).Figure 4

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