Polystyrene microplastics, extensively considered endocrine disrupting chemicals, disturb the reproductive system of living organisms. Polycystic ovary syndrome (PCOS), the reproductive endocrinopathy, is longstanding concern due to its eternal impacts as reproductive disorder and infertility. Despite several reports in reproductive and endocrine toxicity, there is inadequate literature regarding the daily intake of polystyrene-microplastics via drinking water in causing PCOS and leading to ovarian fibrosis in long-term. The present study investigated whether daily consumption of polystyrene-microplastics at doses equivalent to human exposure can cause PCOS and progress to ovarian fibrosis, using female zebrafish as model. Resembling letrozole-PCOS zebrafish model, daily intake of polystyrene-microplastics displayed hallmark PCOS pathophysiology; like excess body weight and %Gonadosomatic index, decreased Follicle Stimulating Hormone and β-estradiol, increased Luteinising Hormone, brain and ovarian Testosterone (39.3% and 75% respectively). Correspondingly, ovarian histology revealed more developing (stage I and II) oocytes and less mature oocytes alongwith cystic lesions; like follicular membrane disorganization, zona pellucida invagination, theca hypertrophy, basophilic granular accumulation and oocyte buddings. Lipid deposition in intestinal and ovarian tissues was evidenced and increased fasting blood glucose manifesting insulin resistance. The expression of PCOS biomarkers (tox3, dennd1a, fem1a) was significantly disturbed. Polystyrene microplastics played vital role in inducing PCOS further enhancing oxidative stress, which positively influences inflammation and aggravate ovarian mitophagy, shedding light on its ability to harshen PCOS into ovarian fibrosis, which is characterized by collagen deposition and upregulation of pro-fibrogenic biomarker genes. These findings illustrate the potential of daily microplastics intake via drinking water in triggering PCOS and its progression to ovarian fibrosis.
Keyphrases
- polycystic ovary syndrome
- drinking water
- insulin resistance
- oxidative stress
- human health
- blood glucose
- health risk assessment
- adipose tissue
- high fat diet
- metabolic syndrome
- health risk
- skeletal muscle
- type diabetes
- poor prognosis
- systematic review
- gene expression
- body weight
- emergency department
- endothelial cells
- weight gain
- cell proliferation
- signaling pathway
- risk assessment
- high fat diet induced
- glycemic control
- heavy metals
- liver fibrosis
- atomic force microscopy
- multidrug resistant
- fatty acid
- binding protein
- long non coding rna
- genome wide
- body mass index
- induced apoptosis
- diabetic rats
- electronic health record
- ischemia reperfusion injury