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Updated: Sep 26, 2026
A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
Dibromochloropropane inhibits spermatogonial development in rats
Marvin L Meistrich1, Gene Wilson, Gladis A Shuttlesworth
1M.D. Anderson Cancer Center, Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. meistrich@mdanderson.org
Abstract:
Exposure to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia in men. There are questions regarding the cellular targets resulting in this effect. In this study we characterized an animal model, in which four daily injections of DBCP produced prolonged oligospermia in LBNF(1) rats without any indication of recovery. Between 6 and 20 weeks after DBCP treatment, 70% of seminiferous tubules showed an epithelium with Sertoli cells but no differentiating germ cells. About 20% of tubules contained differentiating germ cells and 10% showed occlusion or major morphologic alterations to Sertoli cells. Since gonadotropin levels and intratesticular testosterone (ITT) concentrations were elevated in the DBCP-treated rats, the failure of spermatogonial development could not have been a result of lack of these hormones. The tubules without differentiating germ cells contained actively proliferating and dividing type A spermatogonia, which underwent apoptosis instead of differentiation. Thus, the target for the damaging effect appears not to be the killing of stem spermatogonia, but the loss of their ability to undergo differentiation. The presence of type A spermatogonia in the atrophic tubules indicates the potential for intervention to restore spermatogenesis.
Insights
Dibromochloropropane (DBCP) exposure causes infertility by preventing germ cell differentiation, not by killing stem cells. This finding in rats suggests potential interventions to restore sperm production.
Area of Science:
- Reproductive Toxicology
- Spermatogenesis Research
- Nematocide Effects
Background:
- Dibromochloropropane (DBCP) is a nematocide linked to male infertility (oligozoospermia and azoospermia).
- The precise cellular mechanisms underlying DBCP-induced infertility remain unclear.
- Understanding the cellular targets is crucial for developing potential treatments.
Purpose of the Study:
- To characterize an animal model for studying DBCP's effects on spermatogenesis.
- To identify the specific cellular targets responsible for DBCP-induced infertility.
- To explore potential avenues for restoring spermatogenesis after DBCP exposure.
Main Methods:
- LBNF(1) rats were administered four daily injections of DBCP.
- Testicular histology, germ cell differentiation, and Sertoli cell morphology were assessed.
- Gonadotropin levels and intratesticular testosterone (ITT) were measured.
Main Results:
- DBCP induced prolonged oligospermia in rats with no signs of recovery.
- 70% of seminiferous tubules lacked differentiating germ cells, containing only Sertoli cells and proliferating type A spermatogonia.
- Elevated gonadotropins and ITT suggest the damage is not due to hormonal deficiency; type A spermatogonia underwent apoptosis instead of differentiating.
Conclusions:
- DBCP's primary damaging effect is the disruption of germ cell differentiation, not the destruction of stem spermatogonia.
- The presence of viable type A spermatogonia indicates a potential window for therapeutic intervention.
- This animal model provides insights into the cellular basis of DBCP toxicity and potential strategies for fertility restoration.
