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Published on: July 29, 2019
Damage response and postnatal compensatory repair in the male offspring mouse reproductive system following
Jiaoqiao Zhu1, Ankai Tan2, Yixuan Lu2
1College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Guangling College of Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China; Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.
Abstract:
Cadmium (Cd), an environmental toxicant, is known to cause significant damage to reproductive systems in human and animals. However, the detrimental effects of maternal Cd exposure during gestation on male offspring and the underlying mechanisms remain unknown. In this study, pregnant mice were exposed to Cd (32 mg/l) in drinking water throughout gestation to investigate the mechanisms underlying testicular and sperm injury and repair in male offspring. Results showed that maternal Cd exposure caused growth inhibition in male offspring at birth, accompanied by testicular DNA damage and upregulation of Rad51, a key protein involved in homologous recombination repair. After delivery, when Cd was removed, the male offspring exhibited compensatory growth and development. At 7 weeks of age, despite abnormally enlarged seminiferous tubules, spermatogonial stem cell meiosis arrest, and reduced total sperm motility, DNA damage levels, DNA repair capacity, and the motility function of surviving sperm were all at normal levels. Compared with controls, the offspring at 7 weeks of age showed no alterations in global 5-methylcytosine (5-mC) of sperm, whereas DNA methylation of Line1 were decreased. Meanwhile, DNA methylation of imprinted genes H19 and Peg3, which regulate sperm quality and post-fertilization embryonic development, remained normal. Cd exposure during gestation led to transcriptomic abnormalities in the testes of newborn male offspring, but these abnormalities were gradually repaired during postnatal growth and development. These findings indicate that although gestational Cd exposure impairs reproductive function of male offspring, postnatal growth and development, coupled with DNA repair mechanisms, can partially restore their reproductive potential.
Insights
Maternal cadmium exposure during pregnancy harms male offspring's reproductive health. However, postnatal development and DNA repair mechanisms help partially restore sperm function and reproductive potential in these offspring.
Area of Science:
- Reproductive Toxicology
- Developmental Biology
- Environmental Health
Background:
- Cadmium (Cd) is an environmental toxicant known to damage reproductive systems.
- The effects of maternal cadmium exposure during gestation on male offspring reproductive health and underlying mechanisms are not well understood.
Purpose of the Study:
- To investigate the detrimental effects of maternal cadmium exposure during gestation on male offspring's testicular and sperm health.
- To elucidate the mechanisms of testicular and sperm injury and repair in male offspring following gestational cadmium exposure.
Main Methods:
- Pregnant mice were exposed to cadmium (32 mg/l) in drinking water throughout gestation.
- Male offspring were assessed at birth and at 7 weeks of age for growth, testicular DNA damage, sperm parameters, DNA repair capacity, and DNA methylation patterns.
- Transcriptomic analysis was performed on testes of newborn male offspring.
Main Results:
- Maternal cadmium exposure caused growth inhibition, testicular DNA damage, and Rad51 upregulation in newborn male offspring.
- Despite initial impairments, male offspring showed compensatory growth post-delivery.
- At 7 weeks, although seminiferous tubules were enlarged and meiosis arrested, surviving sperm exhibited normal DNA damage levels, repair capacity, and motility.
- Global sperm 5-methylcytosine was unchanged, but Line1 DNA methylation decreased, while imprinted genes H19 and Peg3 methylation remained normal.
- Testicular transcriptomic abnormalities in newborns were gradually repaired during postnatal development.
Conclusions:
- Gestational cadmium exposure impairs male offspring's reproductive function.
- Postnatal growth, development, and DNA repair mechanisms contribute to the partial restoration of reproductive potential in male offspring exposed to cadmium in utero.
- This study highlights the resilience of the male reproductive system to developmental toxicant exposure through repair and compensatory mechanisms.