FSHR-targeting tetrahedral DNA frameworks ameliorate ovarian aging through oxidative stress elimination

Yun Dai1,2,3, Yican Guo1,2,3, Dan Chen1,2,3

  • 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

PubMed

Insights

This study introduces FSH-DTN, a novel nanoparticle that targets the ovaries to combat oxidative stress and delay ovarian aging. It demonstrates superior antioxidant and anti-aging effects, offering a new strategy for preserving ovarian function.

Area of Science:

  • Reproductive biology
  • Gerontology
  • Nanomedicine

Background:

  • Ovarian aging, marked by reduced ovarian reserve, accelerates female aging.
  • Oxidative stress drives ovarian aging through apoptosis, mitochondrial dysfunction, and inflammation.
  • Existing antioxidants lack proven efficacy and have side effects, necessitating novel solutions.

Purpose of the Study:

  • To develop and evaluate FSH-DTN, a targeted nanoparticle for ovarian delivery.
  • To assess FSH-DTN's efficacy in mitigating oxidative stress and delaying ovarian aging.
  • To elucidate the mechanisms underlying FSH-DTN's protective effects on ovarian function.

Main Methods:

  • Development of FSH-DTN, a DNA tetrahedral nanostructure with a follicle-stimulating hormone receptor-targeting peptide.
  • In vivo imaging to confirm ovarian targeting efficiency of FSH-DTN.
  • In vitro and in vivo models of acute, subacute, and chronic ovarian aging to evaluate FSH-DTN's effects.
  • Analysis of ROS scavenging, apoptosis, NRF2 pathway activation, and ovarian function.

Main Results:

  • FSH-DTN exhibited enhanced ovarian accumulation compared to native DTN.
  • FSH-DTN demonstrated significant antioxidant, anti-apoptotic, and anti-aging effects in ovarian aging models.
  • FSH-DTN directly scavenged reactive oxygen species (ROS) and activated the NRF2 pathway, boosting endogenous antioxidant capacity.
  • Ovarian function was protected by FSH-DTN treatment.

Conclusions:

  • FSH-DTN is a promising nanotherapeutic for targeting ovarian aging.
  • This targeted nanoparticle effectively neutralizes ovarian oxidative stress.
  • FSH-DTN represents a novel strategy to delay ovarian aging and preserve reproductive health.

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