Effect Of Prenatal Exposure To Diethylstilbestrol On Gonadotrophins And Their Receptors On Testis Development In Offspring Male Mice

Objective: There was great concern that the incidence of congenital disorders of male sexual differentiation was rapidly increasing. Recently, it has been shown that low-dose exogenous estrogen caused congenital disorders in fetal rodents and some effect is adverse with high-dose. However, all the mechanism remained unclear. The aim of this research was to investigate the effect of prenatal exposure to low-dose versus high-dose diethylstilbestrol (DES) and the changes of gonadotrophins and their receptors in testis development in male offsprings of Kunming mice. In this study, histological analysis and light microscope were also used to observe the effects of DES on on testis development in offspring male mice.Materials and methods: 200 8-10 weeks old Kunming female mice were divided into eight groups randomly, that is, normal group (not given any drug), control group (given DMSO and 9%NS), and experimental groups 1-6: DES were be given 100.0, 50.0, 25.0, 10.0, 0.5 and 0.1μg.kg-1.d-1 respectively (DES dissolved in DMSO and NS). Female mice were placed in individual cages with male mice and the morning when a vaginal plug appeared was designated as gestation day 0 (GD0). Pregnant mice were injected subcutaneously on GD9 though GD17 with DES in DMSO and NS or with DMSO and NS (controls). The day of birth was designated as day 0, and male offspring mice were sacrificed on Days 0, 5, 15, 25, 35, 45 and 60. The testes were harvested and prepared for hemyotoxin-eosin (HE) and immunohistochemistry study, including LH, LHR, FSH and FSHR. The expression intensity was quantitated by image analysis in terms of their gray scales, and statistically analyzed thereafter.Results: 1. Severe atrophy of seminiferous epithelium and spermatozoa decrease of mice were found in the DES high doses group (DES100.0 and DES50.0μg.kg^-1.d^-1 groups). 2. Expressions of LH and LHR continuesly increase by the time from birth to day 60, and before day 25, the increase was slow, when day 35, they increase sharply. The expressions of LH were positively relate to that of LHR (r=0.995, P<0.05) 3. Expressions of FSH and FSHR also increase continuesly by the time from birth to day...