Developmental effects on hypothalamic, hypophyseal, testicular and steroidogenic patterns of sertraline-exposed male rats by accumulated doses from juvenile to puberty

Since the enduring exposure to selective serotonin reuptake inhibitors medications from juvenile period to puberty poses a growing concern, the aim is an attempt to evaluate the reproductive aspects of sertraline-treated postnatal male rats. Total 80 male rats were orally given 1.2 mg/kg bw/day from postnatal day 28 to puberty (balano-preputial separation). Necropsy takes place at 56th, 84th, 126th postnatal day (SGII, SGIII, and SGIV, respectively), along with the control group (SGI). Final body weight, weight gain, and weights of liver, kidneys, testes and epididymis were significantly decreased in the SGIII and SGIV groups compared to the controls. Levels of LH, FSH, and testosterone and 17 beta-HSD concentrations were significantly decreased in all groups. Male rats in SGIV group displayed a significant decline in sperm counts, motility and viability and increase in sperm morphological defects compared to control. The cumulative dose of 1.2 mg/kg of sertraline at the 126th postnatal days produced a significant depression in male virility (mating and fertility indices) compared to the control group. In addition, the cumulative treatment significantly increased the number of fetal resorptions in outcomes of female rats copulated by males in the SGIV group and decrease in both the number of implant sites and the viable fetuses. It is concluded that the sertraline-mediated reproductive deficits could entirely dependent on the robust spreading of the serotonergic receptors in the Leydig, Sertoli and germ cells, testis, epididymis, and vas deferens and simultaneously on the developmental-mediated timing of reproductive processes during the postnatal period to puberty.