Polyethylene microplastics disrupt focal adhesion kinase (FAK) signaling and sertoli cell metabolism, compromising blood-testis barrier function and spermatogenesis

Polyethylene microplastics (PE-MPs), used extensively in personal care applications, are non-biodegradable pollutants with demonstrated bioaccumulation potential and toxicological relevance. Recent studies have detected microplastics in human semen and testicular tissues, raising concerns about their effect on male reproductive health. This study investigates the toxicological effects of orally administered polyethylene microplastics (PE-MPs) at 20 µg/mL, 200 µg/mL, and 2000 µg/mL doses in rats for 56 days, with a focus on disruption of the blood-testis barrier (BTB) and destabilization of ectoplasmic specialization (ES), both essential for normal spermatogenesis. Western blot analysis showed a marked reduction in BTB-associated tight junction proteins occludin, claudin-11, N-cadherin, E-cadherin, and adaptor protein ZO-1, as well as the steroidogenic marker StAR in PE-MPs-treated rats, indicating disruption of barrier integrity and steroidogenic function. PE-MPs exposure significantly reduced p-FAK (Tyr407), could impair the F-actin organization, and lead to an open BTB. At the same time, increased p-FAK (Tyr397) expression resulted in decreased spermatid adhesion, disrupting apical ES dynamics and contributing to a leaky BTB with increased permeability. These alterations led to spermiation failure, premature germ cell exfoliation, and impaired spermatogenesis. Additionally, the Akt and mammalian rapamycin (mTOR) expression targets were explored to understand their potential role in PE-MPs-induced testicular toxicity. The exposure to PE-MPs significantly altered 17 serum metabolites, indicating metabolic disturbances identified through ¹H NMR metabolomics. High doses of PE-MPs significantly elevated serum pyruvate and lactate levels in rats, possibly infiltrating the testis due to disruption of the BTB. Also, PE-MPs exposure significantly elevated the serum histidine-to-tyrosine ratio, indicating disrupted amino acid metabolism. These findings demonstrate that PE-MPs compromise BTB integrity, disrupt ES dynamics, impair spermatogenesis, and induce systemic metabolic alterations, highlighting their potential risk to male reproductive health.