Nuclear Morphometric Analysis of Leydig Cells of Male Pubertal Rats Exposed <i>In Utero</i> to Di(<i>n</i>-butyl) Phthalate

Abstract

We recently reported that prenatal rat exposure to di(n-butyl) phthalate (DBP) induced Leydig cell (LC) hyperplasia after nine weeks (wks) of age, yet the number of LCs was similar to that of the vehicle group until seven weeks. Nuclear pleomorphism of hyperplastic LCs is common and is considered to be continuous progressive degeneration. Thus, computer-assisted image cell nuclear analysis of LCs was performed on 5- and 7-wk-old Sprague-Dawley (SD) rats whose dams had been administered DBP (i.g.) at 100 mg/kg/day or vehicle (corn oil) on gestation day 12 to 21. The results of the 5-wk-old DBP group were similar to those of the vehicle group; LC nuclei of the 7-wk-old DBP group showed normal ploidy and similar amounts of DNA. However, the size, elongation and peripheral chromatin aggregation parameters were significantly higher, and the reticular chromatin distribution and isolated chromatin aggregation parameters were significantly lower compared with the vehicle group. The present study quantitatively demonstrated nuclear morphological alterations in rat LCs at 7 wks old (puberty) due to the prenatal DBP administration before apparent LC hyperplasia developed.

Changes in testicular histomorphometry and ultrastructure of Leydig cells in adult male Japanese quail exposed to di (n-butyl) phthalate (DBP) during the prepubertal period

“…Several qualitative (Alam et al 2010a ; Ahbad and Barlas 2013 ; Moody et al 2013 ; Shirai et al 2013 ; Shono and Taguchi 2014 ) and quantitative (Auharek et al 2010 ; Wakui et al 2013 ) studies have been performed in order to detect testicular toxicity due to PE exposure in animals. Relatively, quantitative studies on the seminiferous tubule epithelium have received very little attention.…”

“…Exposure of adult male rats to high doses of certain phthalates resulted in rapid and severe changes in the testis (Dalgaard et al 2001 ). In testicular tissues, the primary cellular target of phthalate-induced exposure are Sertoli and/or Leydig cells, which exhibit biochemical and morphological changes (Moffit et al 2007 ; Shirai et al 2013 ; Wakui et al 2013 ; Bello et al 2014 ; 2019 ).…”

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate

“…Animal studies show that administration of DBP could elicit antiandrogenic effects in offspring, such as shortened anogenital distance (AGD), hypospadias, cryptorchidism, and spermatogenesis dysfunction (Baskin et al, ; Steinhardt, ; Foster, ; Jiang et al, ; Hsieh et al, ; Kalfa et al, ). Although the potential effects of DBP have aroused extensive attention (Kim et al, ; Chen et al, ; Wakui et al, ; Bhatia et al, ; Hu et al, ; Zuo et al, ), there were few animal experiments available indicating the toxicity of DBP on the development of anorectum.…”