Development of reproductive tract lesions in male F344 rats after treatment with dimethyl methylphosphonate.
Dimethyl methylphosphonate (DMMP) is an organophosphorous compound that impairs fertility in male rodents. In previous studies, male rats treated with DMMP had decreased sperm motility and count, and sired fewer litters with fewer pups per litter. The following studies examined the development of the reproductive lesions by light and electron microscopy after treatment with DMMP. Adult male F344 rats were treated po with DMMP, 1750 mg/kg, for up to 12 weeks. Tissues were perfused in situ with Karnovsky's fixative and embedded in glycol methacrylate. After 5 weeks of treatment there were occasional PAS-positive bodies in lumina of tubules in stages XII-III. These were ultrastructurally similar to cytoplasm of step 12-17 spermatids. After 7 weeks of treatment, there was an increase in the number of tubules exhibiting these bodies, as well as an increase in the number of tubules showing delayed or early spermiation, or focal exfoliation of nonnecrotic cap-phase spermatids and some spermatocytes. No multinucleated giant cells were seen. Focal loss of germ cells occurred more frequently as duration of exposure increased, and occupied 5-100% of an affected tubule. Frequently, an area of germ cell exfoliation occurred adjacent to areas of normal tubular epithelium. These lesions were not specific to any particular stages of spermatogenesis. Occasionally, elongating spermatids were without rib elements of the fibrous sheath in the tail; these were not seen in epididymal sections. Animals left to recover for 14 weeks after treatment showed approximately 80% normal tubules; affected tubules varied in their degree of recovery, but all showed the loss of normal epithelial organization, a characteristic of DMMP treatment. Epididymal epithelium was not visibly affected by treatment with DMMP. DMMP produced morphologic alterations in Sertoli cells and elongating spermatids, as well as producing functional defects in spermatozoa.
D000818:Animals; D003593:Cytoplasm / Q000473:pathology; D004822:Epididymis / Q000473:pathology*; D007248:Infertility, Male / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013087:Spermatids / Q000473:pathology; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology*; D013997:Time Factors
D009943:Organophosphorus Compounds; C031116:dimethyl methylphosphonate