The morphological development of di‐n‐pentyl phthalate induced testicular atrophy in the rat

Abstract

Prepubertal rats treated orally with di-n-pentyl phthalate at 2.2 g/kg body weight were killed at 1, 3, 6 and 24 hr following a single dose, and after 2, 3 and 4 days of repeated daily dosing. At 3 hr Sertoli cells in a proportion of the seminiferous tubules showed vacuolation of the perinuclear smooth endoplasmic reticulum with an associated inward displacement of germinal cells. By 6 hr the vacuolation had extended to the apical cytoplasm and was evident in most tubules. Early degenerative changes were also apparent in spermatocytes and spermatids and were accompanied by an acute interstitial inflammatory infiltrate. By 24 hr, germinal cell degeneration was extensive with desquamation and general disorganisation of cell layers within the epithelium, but the interstitial inflammatory infiltrate had declined. Mitochondrial succinic dehydrogenase activity in Sertoli cells was reduced at 3 and 6 hr and absent by 24 hr. In germinal cells it was unaffected at 3 and 6 hr but absent by 24 hr. Two, three and four days of daily phthalate treatment resulted in a gradual depletion of germinal cells from all tubules, leaving a Sertoli cell matrix containing a few necrotic spermatocytes and occasional normal spermatogonia. The significance of the early Sertoli cell changes is discussed.

The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

“…Even though there is only a slight cumulative potential, phthalates are found in a wide variety of extensively used products, have been identified in all environmental compartments, and are a serious concern for the possibility of adverse effects. The acute toxicity of phthalates is low, with LD 50 values ranging from 0.7 to > 20 g/kg (27); however, changes in lipid metabolism (28)(29)(30), testicular atrophy (31,32), alterations in xenobiotic metabolism (33,34), liver peroxisome proliferation (35), and carcinogenicity (36,37) have been observed. Regarding reproductive and developmental effects, phthalates vary in potency, with DEHP being the most potent and DBP and BBP roughly an order of magnitude less potent (38)(39)(40)(41)(42)(43)(44)(45).…”

Aspects of the testicular toxicity of phthalate esters.

“…This was found to occur even when measurements were started as early as 1 hr after treatment. However, since morphological changes in the Sertoli cells have been observed at 3 hr after a single dose of DPP (4), it might be anticipated that functional impairment would be evident at an earlier stage. It is generally accepted that the Sertoli cells play a key role in controlling the development and maintenance of spermatogenesis and that they constitute the main functional component of the blood-testis barrier (20)(21)(22)(23).…”

“…In rats, repeated administration of DEHP results in seminiferous tubular atrophy characterized by a loss of the meiotic and post-meiotic germ cell populations from the seminiferous epithelium (4). Certain other esters, such as di-n-butyl-, di-n-pentyl-,and di-n-hexyl phthalate, produce the same lesion whereas others, such as diethyl and di-tert-butyl phthalate, have no effect on the testis (5)(6).…”

“…The lesion is similar in all susceptible species, involving early detachment of spermatocytes and spermatids from the seminiferous epithelium, but little is known of the mechanisms underlying this effect. However, Creasy et al (4) reported that morphological changes were evident in the Sertoli cells within 3 to 6 hr of a single dose of di-n-pentyl phthalate, at which time the germ cell population ap-*British Industrial Biological Research Association, Woodmansterne Road, Carshalton, Surrey SM5 4DS England. peared unaffected.…”

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

“…Besides, they also induce morphologic changes in SCs [98]. Thus, it is expectable that the metabolic cooperation between testicular cells is hampered by phthalates.…”