Sexual maturation and fertility of mice exposed to triphenyltin during prepubertal and pubertal periods

Abstract

This study investigated the effects of pre- and peripubertal exposure (PND 15-45) to triphenyltin hydroxide (TPT: 0, 1.875, 3.75, 7.5 and 15 mg/kg bw/d po) on mouse sexual maturation and fertility. Half of the mice were euthanized on PND 46 and the remaining mice were submitted to fertility tests on PND 65-75. TPT caused a transient decrease of weight gain at 3.75 mg/kg bw/d, and deaths and body weight deficits at higher doses. Delays of testes descent (TD), vaginal opening (VO) and first estrus (FE) occurred at doses ≥3.75 (TD) and ≥7.5 mg/kg bw/d (VO, FE), respectively. Body weight on the days of TD, VO and FE did not differ among groups. TPT at doses ≥3.75 mg/kg decreased sperm and spermatid counts at the end of treatment (PND 46) but no alteration was noted later on PND 75. Testicular histopathology (PND 46) showed a dose-dependent reduction of seminiferous tubules diameter, a greater degree of vacuolation in Sertoli cells and germ cell degeneration and necrosis in TPT-treated mice. TPT did not affect the outcome of fertility tests. Study-derived NOAEL was 1.875 mg TPT/kg bw/d for males and 3.75 mg TPT/kg bw/d for females. The detrimental effects of TPT on spermatogenesis were reversed after treatment discontinuation.

Keywords: Fertility; Organotin compounds; Postnatal exposure; Puberty; TPTH; Triphenyltin.

Fig. 1

Body weight gain (g) of male (A) and female (B) mice treated orally (gavage) with triphenyltin hydroxide (0, 1.875, 3.75, 7.5 or 15 mg/kg bw/d) suspended in corn oil from postnatal day 15 through to 45. The height of the histogram bar corresponds to mean ± SD. A star indicates that the mean body weights differ (p < 0.05, ANOVA followed by Bonferroni's post hoc test) from the mean body weight of controls (0 mg/kg bw/d) at the same postnatal day.

Fig. 2

Testicular histology changes in mice treated with triphenyltin hydroxide (0, 1.875, 3.75, 7.5 or 15 mg/kg bw/d po) from PND 15–45. Mice were euthanized at the end of treatment (PND 46). Testes were fixed in Bouin's solution and Millonig's buffered formalin as modified by Carson and stained with hematoxylin–eosin. Typical histology of a control mouse testis is shown in panel A, while all remaining panels illustrate histological changes found in TPT-treated animals (B, C–E: 1.875 mg/kg bw/d; G: 3.75 mg/kg bw/d; D, F, H: 7.5 mg/kg bw/d), such as an increased degree of vacuolation of Sertoli cells (panels E, F, asterisk *), vacuole apparently associated with germ cell deaths (panel D, asterisk *), acidophilic cells with pyknotic nuclei and hypercondensation of chromatin (panels G and H, arrows), multinucleated cell aggregates (panels B and C, arrow head). Magnification: 400×.