Abstract
The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.
Highlights
The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation that this effect is highly dependent on the time, duration and level of exposure [1,2,3].Exposure to exogenous steroids, due to industrial pollutants [4], could affect the developing fetus
The percent of male offspring and mortality rate The percentage of male offspring born from mothers treated with testosterone in both experimental groups І and П did not differ compared to their controls (Table S1)
The mortality rate of the male offspring in both experimental groups did not differ significantly compared to their controls, at different days of examination (Table S1)
Summary
The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation that this effect is highly dependent on the time, duration and level of exposure [1,2,3].Exposure to exogenous steroids, due to industrial pollutants [4], could affect the developing fetus. The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation that this effect is highly dependent on the time, duration and level of exposure [1,2,3]. There are several studies that demonstrated the impact of prenatal exposure of female fetuses to excess androgen, such studies in male offspring are limited. Experimental induction of androgen excess during prenatal or early postnatal life, in female animal models has been shown to reprogram reproductive and metabolic physiology, resulting in irregular, intermittent or absent estrous cycles, hyperandrogenism and polycystic ovarian morphology [3,6], manifestations are highly dependent on the time and the amount of androgens used. It has been demonstrated that androgen-mediated development of a normal male reproductive system occurs via androgen "programming" within a specific fetal time window (embryonic days 15.5-18.5) in the rat, that precedes morphological differentiation and development of the relevant tissues [7]
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