Testicular dysfunction and "its recovery effect" after cadmium exposure

Area of Science:

• Environmental toxicology
• Reproductive biology
• Endocrinology

Background:

• Industrialization increases heavy metal exposure, raising concerns about male fertility decline.
• Cadmium is a prevalent environmental pollutant linked to reproductive toxicity.
• The reversibility of cadmium-induced testicular dysfunction requires further investigation.

Purpose of the Study:

• To investigate the reversibility of testicular damage and male fertility impairment following cadmium exposure cessation.
• To elucidate the underlying molecular mechanisms, including hormonal axis regulation and signaling pathways.
• To assess the role of corticosterone in regulating spermatogonial function.

Main Methods:

• Construction of rat models with controlled cadmium exposure and subsequent withdrawal (dis-exposure).
• Monitoring of key reproductive parameters, including fertility, hormone levels, and testicular function indicators.
• Analysis of testicular signaling pathways, such as glucocorticoid receptor (GR)/PI3K-AKT/AMPK.
• In vitro experiments using corticosterone on spermatogonia.

Main Results:

• Cadmium exposure reduced fertility, inhibited the hypothalamic-pituitary-testis axis, activated the hypothalamic-pituitary-adrenal axis, and altered testicular GR/PI3K-AKT/AMPK signaling.
• Testicular cell proliferation was inhibited, and apoptosis was enhanced following cadmium exposure.
• Four weeks post-cessation, fertility remained reduced, but indicators showed signs of reversal.
• Eight weeks post-cessation, all observed indicators returned to normal levels.
• Corticosterone was confirmed to potentially regulate spermatogonial proliferation and apoptosis via the GR/PI3K-AKT/AMPK pathway.

Conclusions:

• Cadmium exposure induces significant reproductive toxicity in male rats, affecting fertility and testicular function.
• The observed testicular damage and fertility impairment are reversible upon cessation of cadmium exposure, with full recovery at eight weeks.
• The GR/PI3K-AKT/AMPK signaling pathway and corticosterone play crucial roles in mediating cadmium's effects and the subsequent recovery process.