Prenatal testosterone supplementation alters puberty onset, aggressive behavior, and partner preference in adult male rats

Abstract

The objective of this study was to investigate whether prenatal exposure to testosterone (T) could change the body weight (BW), anogenital distance (AGD), anogenital distance index (AGDI), puberty onset, social behavior, fertility, sexual behavior, sexual preference, and T level of male rats in adulthood. To test this hypothesis, pregnant rats received either 1 mg/animal of T propionate diluted in 0.1 ml peanut oil or 0.1 ml peanut oil, as control, on the 17th, 18th and 19th gestational days. No alterations in BW, AGD, AGDI, fertility, and sexual behavior were observed (p > 0.05). Delayed onset of puberty (p < 0.0001), increased aggressive behavior (p > 0.05), altered pattern of sexual preference (p < 0.05), and reduced T plasma level (p < 0.05) were observed for adult male rats exposed prenatally to T. In conclusion, the results showed that prenatal exposure to T was able to alter important aspects of sexual and social behavior although these animals were efficient at producing descendants. In this sense more studies should be carried to evaluated the real impact of this hormonal alteration on critical period of sexual differentiation on humans, because pregnant women exposed to hyperandrogenemia and then potentially exposing their unborn children to elevated androgen levels in the uterus can undergo alteration of normal levels of T during the sexual differentiation period, and, as a consequence, affect the reproductive and behavior patterns of their children in adulthood.

Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood

“…In this study, except for reduction of sperm motility, the other effects (reduction of Sertoli cells, Spermatocyte and Spermatid, sperm count and testosterone concentration), were not observed in male rats exposed to exogenous testosterone at day 20 of their fetal life; this could be explained by the difference in time exposure to androgen as in experimental group І it was administered during the male programming window [14], and time of first peak of sexual differentiation of hypothalamus [10], therefore resulted in more severe effects on reproductive function. The rats of experimental group П were exposed to exogenous testosterone on the last day of the gestational period, therefore the hypothalamus-pituitary-gonad axis had been programmed before.…”

“…Furthermore it has been shown that prenatal exposure of male rat to Di-n-Butyl Phthalate (DBP) (anti-androgen, which reduces androgen level) decreases the activity level of testicular steroidogenic enzymes, as well as testosterone level in adults [16]. Another study demonstrated that prenatal exposure of male rat to testosterone propionate, during days 17-19 of gestation, will lead to reduction of plasma testosterone level during adulthood [10]. Rams exposed to testosterone during their development, showed a higher level of plasma testosterone at 20 weeks of age, while a lower level had been seen at the age of 30 weeks [24].…”

On the Role of Testosterone in Anxiety-Like Behavior Across Life in Experimental Rodents

“…Organization of the neuronal circuits by testosterone and/or its metabolites predetermines the behavioral responses to the activational effects of sex hormones later in life. Besides the sensitive period of early—prenatal and perinatal development ( 15 , 27 ), increasing amount of evidence supports the hypothesis that pubertal hormones (re)organize the brain and determine a variety of adult behaviors during adolescence ( 36 , 37 ) or outside of the classic critical periods of neurodevelopment ( 38 ). An overview of the results of some experiments investigating sex differences and the role of testosterone in anxiety-like behavior, with particular regard to the age of animals with hormone manipulation and analysis of the outcomes, is provided in Table 1 .…”

Sleep and Reproductive Health

“…On the other hand, when the sleep duration was further decreased to mimic the chronic sleep debt present in humans, no significant change in sexual motivation or behavior was observed [54]. Supplementation of testosterone has been observed to be an efficient means of maintaining and improving sexual response in adults and aged male rats [55,56]. There is evidence that the supplementation of testosterone (T) combined with estradiol (E2) shows better results [57].…”