# Protective Effects and Potential Mechanisms of D-Aspartate on Testicular Damage Induced by Polystyrene Microplastics

**Authors:** Sara Falvo, Giulia Grillo, Imed Messaoudi, Nada Fradi, Gabriella Chieffi Baccari, Maria Maddalena Di Fiore, Alessandra Biasi, Maria Rosaria Ambruosi, Alessandra Santillo, Massimo Venditti

PMC · DOI: 10.3390/biom15111484 · 2025-10-22

## TL;DR

This study shows that D-aspartate can protect rat testicles from damage caused by polystyrene microplastics by reducing oxidative stress and improving sperm production.

## Contribution

This is the first in vivo study to demonstrate the protective effects of D-aspartate against microplastic-induced testicular damage.

## Key findings

- D-aspartate reduced oxidative stress and apoptosis in testicular tissue exposed to polystyrene microplastics.
- D-aspartate restored steroidogenesis and spermatogenesis by normalizing key marker proteins.
- The amino acid mitigated autophagy activation induced by microplastics.

## Abstract

Polystyrene Microplastics (PS-MPs) affect testicular activity, as evidenced by increased oxidative stress, apoptosis, and autophagy activation, impairing steroidogenesis and spermatogenesis. The present study investigates, for the first time in vivo, the potential protective effect of D-aspartate (D-Asp) against PS-MPs-induced damage on the testicular function of adult rats. D-Asp, well-known stimulator of testosterone biosynthesis and spermatogenesis progression, possesses pharmacological properties, including antioxidant and anti-apoptotic ones. The results showed that PS-MP’s adverse effects on testicular activity were reversed by D-Asp treatment. Mechanistically, D-Asp inhibited testicular oxidative stress by modulating the protein levels of CAT, SOD1, SOD2, and 4-HNE; affecting TBARS levels; and reducing apoptosis, as suggested by CYT C analysis and a TUNEL assay. Furthermore, D-Asp administration mitigated PS-MPs-induced autophagy activation by modulating the expression of LC3BI, LC3BII, and p62 proteins. Finally, the amino acid counteracts PS-MPs damage on steroidogenesis and spermatogenesis by restoring normal levels of steroidogenic (StAR, 3β-HSD, and 17β-HSD) and spermatogenic (PCNA and SYCP3) markers. This study encourages further research to understand the potential value of the amino acid in improving human testicular health and male fertility.

## Linked entities

- **Genes:** CAT (catalase) [NCBI Gene 847], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], SOD2 (superoxide dismutase 2) [NCBI Gene 6648], GTF2H1 (general transcription factor IIH subunit 1) [NCBI Gene 2965], STAR (steroidogenic acute regulatory protein) [NCBI Gene 6770], 3BHSD (3beta-hydroxysteroid dehydrogenase/isomerase) [NCBI Gene 100860869], Hsd17b4 (hydroxysteroid (17-beta) dehydrogenase 4) [NCBI Gene 15488], PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111], SYCP3 (synaptonemal complex protein 3) [NCBI Gene 50511]
- **Proteins:** CAT (catalase), SOD1 (superoxide dismutase 1), SOD2 (superoxide dismutase 2), GTF2H1 (general transcription factor IIH subunit 1), STAR (steroidogenic acute regulatory protein), 3BHSD (3beta-hydroxysteroid dehydrogenase/isomerase), Hsd17b4 (hydroxysteroid (17-beta) dehydrogenase 4), PCNA (proliferating cell nuclear antigen), SYCP3 (synaptonemal complex protein 3)
- **Chemicals:** D-aspartate (PubChem CID 83887), 4-HNE (PubChem CID 5283344), CYT C (PubChem CID 16057918)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CAT (catalase) [NCBI Gene 847], STAR (steroidogenic acute regulatory protein) [NCBI Gene 6770] {aka STARD1}, HSD17B1 (hydroxysteroid 17-beta dehydrogenase 1) [NCBI Gene 3292] {aka 17-beta-HSD, 20-alpha-HSD, E2DH, EDH17B2, EDHB17, HSD17}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, SYCP3 (synaptonemal complex protein 3) [NCBI Gene 50511] {aka COR1, RPRGL4, SCP3, SPGF4}, NUP62 (nucleoporin 62) [NCBI Gene 23636] {aka IBSN, SNDI, p62}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283] {aka 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}
- **Chemicals:** 4-HNE (-), Polystyrene (MESH:D011137), PS (MESH:D010758), amino acid (MESH:D000596), testosterone (MESH:D013739), D-Asp (MESH:D026603), TBARS (MESH:D017392)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12650146/full.md

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Source: https://tomesphere.com/paper/PMC12650146