Intraovarian condensed platelet cytokines for infertility and menopause—Mirage or miracle?

Sills, E. Scott; Wood, Samuel H.; Walsh, Anthony

doi:10.1016/j.biochi.2022.08.020

Cited by 6 publications

(2 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While Mercado et al [ 17 ] were among the first to suggest that N-glycan surface features on platelets are influenced by 5-Hydroxytryptophan (5-HT), many 5-HT/serotonin-specific receptors are also known to be on oocytes and within ovarian tissue more generally [ 18 ]. Interactions between platelet cargo proteins and follicular surface markers following ovarian PRP invite interest because membrane dynamics determine cellular homeostasis via ion transport and modulation of key signaling pathways [ 19 , 20 ].…”

Section: Post-translational Effects and Telomere Considerationsmentioning

confidence: 99%

Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

Sills

Wood

2023

Medicines

Self Cite

View full text Add to dashboard Cite

Platelet-rich plasma (PRP) is an ‘orthobiologic’ with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, ‘ovarian rejuvenation’. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors. However, if the observed effect of rectifying embryo ploidy error can be proven beyond case reports and small series, activated PRP (or its condensed plasma cytokines) would deliver a welcome therapeutic disruption that is difficult to overstate. Because shortcomings in ovarian function are presently addressed mainly by pharmacological approaches (i.e., via recombinant gonadotropins, GnRH analogs, or luteal support), autologous PRP would represent an unusual departure from these interventions. Given the diversity of platelet cargo proteins, the target response of intraovarian PRP is probably not confined to oocytes or follicles. For example, PRP manipulates signal networks driving improved perfusion, HOX regulation, N-glycan post-translational modification, adjustment of voltage-gated ion channels, telomere stabilization, optimization of SIRT3, and ribosome and mitochondria recovery in older oocytes. While multichannel signals operating on various pathways are not unique to reproductive biology, in intraovarian PRP this feature has received little study and may help explain why its standardization has been difficult. Against this background, our report examines the research themes considered most likely to shape clinical practice.

show abstract

Section: Post-translational Effects and Telomere Considerationsmentioning

confidence: 99%

Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

Sills

Wood

2023

Medicines

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, mTORC1 is inhibited at low nM levels of rapamycin while mTORC2 suppression usually requires chronic use at higher concentrations [67]. PI3 K/Akt works with Hippo signaling to accelerate recruitment of primordial follicles, while mTORC1 suppression suppresses uncoordinated 'flash' discharges resulting in mass follicular activation [9,68]. Platelet-rich plasma (or its condensed cytokine derivatives) plus rapamycin has not been previously studied, probably because both treatments are somewhat novel and available research on each is lacking.…”

Section: Rapamycin-scheduling and Toxicity Issuesmentioning

confidence: 99%

mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?

Sills

Harrity

Wood

et al. 2023

JPM

Self Cite

View full text Add to dashboard Cite

No major breakthroughs have entered mainstream clinical fertility practice since egg donation and intracytoplasmic sperm injection decades ago, and oocyte deficits secondary to advanced age continue as the main manifestation of diminished ovarian reserve. In the meantime, several unproven IVF ‘accessories’ have emerged including so-called ovarian rejuvenation which entails placing fresh autologous platelet-rich plasma (PRP) directly into ovarian tissue. Among cellular responses attributed to this intervention are reduced oxidative stress, slowed apoptosis and improved metabolism. Besides having an impact on the existing follicle pool, platelet growth factors might also facilitate de novo oocyte recruitment by specified gene upregulation targeting uncommitted ovarian stem cells. Given that disordered activity at the mechanistic target of rapamycin (mTOR) has been shown to exacerbate or accelerate ovarian aging, PRP-discharged plasma cytokines combined with mTOR suppression by pulsed/cyclic rapamycin represents a novel fusion technique to enhance ovarian function. While beneficial effects have already been observed experimentally in oocytes and embryos with mTOR inhibition alone, this proposal is the first to discuss intraovarian platelet cytokines followed by low-dose, phased rapamycin. For refractory cases, this investigational, tailored approach could amplify or sustain ovarian capacity sufficient to permit retrieval of competent oocytes via distinct but complementary pathways—thus reducing dependency on oocyte donation.

show abstract

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis

Wu,

Su,

Luo

et al. 2024

Platelets

View full text Add to dashboard Cite

Intraovarian condensed platelet cytokines for infertility and menopause—Mirage or miracle?

Cited by 6 publications

References 77 publications

Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

mTOR Inhibition via Low-Dose, Pulsed Rapamycin with Intraovarian Condensed Platelet Cytokines: An Individualized Protocol to Recover Diminished Reserve?

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis

Contact Info

Product

Resources

About