Gestational exposure to silver nanoparticles enhances immune adaptation and protection against streptozotocin-induced diabetic nephropathy in mice offspring

Abstract

Silver nanoparticles (AgNPs) possess unique antimicrobial properties. As a result, they are being increasingly used in a wide range of applications. Several studies have shown detrimental effects of AgNPs exposure, including inflammation, accumulation, and cellular damage to different organs. However, the effect of AgNPs exposure during gestation, a critical and susceptible period of human development, on pregnant females and its long-term effects on offspring’s health has not been studied. Therefore, we conducted a long-term study where we assessed the effect of gestational AgNPs exposure on pregnant mice and followed their offspring until the age of 12 months. Gestational exposure to AgNPs induced systemic inflammation in the pregnant mice at gestational day (GD) 18. Interestingly, developing fetuses exposed to AgNPs, showed anti-inflammatory conditions as indicated by reduced expression of inflammatory genes in fetal organs at GD 18 and reduced serum levels of TNF-α, IFN-γ, IL-17A, IL-6, and MCP-1 in AgNPs exposed pups at postnatal day (PD) 2. Surprisingly, post-weaning, AgNPs exposed offspring showed a heightened immune activation as shown by upregulation of inflammatory cytokines at PD 28, which persisted till late in life. Moreover, we observed metabolic alterations which persisted until adulthood in mice. To understand the impact of long-term immunometabolic changes on the progression of diabetes and kidney diseases under stressed conditions, we exposed offspring to streptozotocin which revealed a protective role of low-dose gestational AgNPs exposure against streptozotocin-induced diabetes and associated nephropathy.

Keywords:

• Silver nanoparticles
• gestational exposure
• immunometabolic alterations
• kidney damage

Acknowledgments

The authors acknowledge the CSIR-Indian Institute of Toxicology Research for the overall support and facilities provided for this research. We acknowledge Advanced Imaging Facility, Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, for providing technical support and imaging under the transmission electron microscope and scanning electron microscope. Some parts of Figure 1(A) and Figure 8 were created with BioRender.com.

Consent form

Consent for publication has been taken from the CSIR- Indian Institute of Toxicology Research, Lucknow, India. The institutional communication number of the manuscript is IITR/SEC/2022-2023/07.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research (CSIR) network project: Nanomaterials: Applications and Impact on Safety, Health, and Environment (NanoSHE).