Reproductive toxicity

Water Dissolution/Oral Gavage for larvae and Oral for adults or Juvenile

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Positive Controls – ICH S5 Reference

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Negative Control – Untreated

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Standard Method - OECD, ICH S5

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Results format – Comprehensive written report with methods and outcomes in MS Word

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Study Sheet with calculations – MS Excel, Phenotype Images

1. Male Fertility Assessments​:

• Sperm Assessment - Spermatogenesis, sperm count, semen quality, testicular damage

• Hormone assessments - Testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)

• Mechanistic and histopathology assessments

• Molecular assessments - DNA fragmentations, ROS levels

• Mating Index, Fertility Index

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2. Female Fertility Assessments:

• Estrous cyclicity, Ovarian failure and Mating behaviour, Ovarian Reserve, 

• Hormone assessments Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and thyroid-stimulating hormone (TSH)

• Conception Rate

• Macroscopic and histopathological examination of ovaries, uterus, oviducts, cervix,

• Molecular assessments - DNA fragmentations, ROS levels

• Mating Index, Fertility Index

Observed effects in zebrafish larvae in earlier studies upon exposure to thalidomide and relevant class of drugs:

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• Pectoral Fin Defects

• Pericardial Edema

• Teratogenic

• Malformations of organs,

• Poor Nerve Development

• Overall Developmental Delays

• Cognitive Toxicity - Aggression, Hyperactivity, Depressive Episodes

• Early mortality

• Tachycardia

• Visceral Edem

• Peripheral Neuropathy

• Bradykinesia

• Skin Sough

• Reduced Feed Intake

• Haemorrhage

• ECG Deviation

• Venous and Arterial Septal Defects

• Hatching Rate

• Circulation

• Preliminary dose-range-finding studies

• Definitive prenatal and postnatal development studies

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Additional Studies in Zebrafish:

• Modified One-Generation Studies

• One-Generation reproduction toxicity

• Two-Generation reproduction toxicity

• Extended one-generation reproductive toxicity

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