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Updated: Aug 6, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
[Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice]
1Demonstration Center for Experimental Basic Medicine Education, Wuhan University, Wuhan 430071, China.
Objective:
To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.
Methods:
Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.
Results:
Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.
Conclusions:
Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.
Insights
Short-term gossypol exposure caused testicular and kidney toxicity in mice. These adverse effects, including reproductive and kidney damage, were reversible after discontinuing gossypol treatment.
Area of Science:
- Toxicology
- Reproductive Biology
- Nephrology
Context:
- Gossypol, a compound derived from cottonseeds, has known toxicological properties.
- Understanding the specific effects of short-term gossypol exposure is crucial for risk assessment.
- Investigating the reversibility of these effects informs potential therapeutic strategies.
Purpose:
- To investigate the toxic effects of short-term gossypol exposure on murine testis and kidney.
- To determine if the observed toxic effects of gossypol are reversible upon cessation of exposure.
Summary:
- Gossypol exposure in mice led to testicular damage, including reduced seminiferous epithelial cells and impaired spermatogenesis.
- Kidney damage manifested as mesangial cell hyperplasia, increased matrix, and reduced mitochondrial ATPase activity.
- Following drug withdrawal, significant recovery in testicular and kidney morphology and function was observed.
Impact:
- Short-term gossypol exposure induces significant reproductive toxicity and nephrotoxicity in mice.
- The study demonstrates the potential for reversibility of gossypol-induced organ damage.
- Findings highlight the importance of considering gossypol's toxicological profile in relevant contexts.
