Effects of chronic mild stress induced from peripuberty on sexual behavior in male rats, with or without escitalopram treatment.

BACKGROUND: After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated. AIMS: To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study. MATERIALS AND METHODS: Forty-four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out. RESULTS: There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram). CONCLUSION: Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation.

Effects of escitalopram treatment and chronic mild stress induced from peripuberty on spermatic parameters of adult rats.

BACKGROUND: The prevalence of depression in adolescents has significantly increased worldwide. Escitalopram is a selective serotonin reuptake inhibitor approved for treatment of psychiatric disorders in children and adolescents by the Food and Drugs Administration. AIMS: This study aimed to evaluate the sperm parameters of adult rats exposed to chronic mild stress (CMS), from peripuberty to adulthood, treated or not with escitalopram. MATERIALS AND METHODS: Sixty-two male rats were distributed into four groups: S - submitted to CMS; E - Escitalopram (10 mg / kg, via gavage); ES - CMS + ES; SC - Sham control. The induced depression protocol consisted of the exposure of the animals to nine different stressors (one stressor/day), randomly for 8 weeks, from peripuberty (41 days postpartum, dpp) to adulthood (97 dpp). The escitalopram treatment period started at 70 dpp and lasted 4 weeks. The euthanasia was performed for biological material collection at 114 dpp. Morphometric, biometric, sperm parameters, oxidative stress analyses, and corticosterone dosage were carried out. RESULTS: There was a reduction of the sperm daily production and sperm concentration in the epididymis of rats treated and/or submitted to CMS. These groups (E, S, ES) also showed reduction of the mitochondrial activity; acrosome integrity; sperm chromatin compaction; sperm motility and vitality, besides an increased frequency of morphologically abnormal sperm. The sperm transit time through the epididymis was significantly higher in the escitalopram-treated rats (E, ES). No differences were observed regarding the sperm DNA fragmentation. The lipid peroxidation was significantly increased at the epididymal (E, S, and ES group) and testicular levels (S group). CONCLUSION: The CMS with or without escitalopram treatment altered the oxidative status in sperm and male organs, worsening the qualitative and quantitative sperm parameters, which can probably compromise the male fertility.

Resveratrol reverses male reproductive damage in rats exposed to nicotine during the intrauterine phase and breastfeeding.

BACKGROUND: Nicotine leads to reproductive changes culminating in male infertility and subfertility. Resveratrol, a polyphenol, is a biological modulator. Sirtuin 1 (SIRT1) protein can positively act on male reproduction, and its expression can be affected by nicotine and modulated by resveratrol. OBJECTIVES: The capability of resveratrol to reverse the reproductive damage in adult male offspring, which was nicotine-exposed during the intrauterine phase and breastfeeding, was investigated. MATERIALS AND METHODS: Four groups were established with male offspring born from nicotine-exposed and non-exposed rat dams during pregnancy and lactation. Forty-eight male Wistar rats were distributed into four groups: sham control (SC), resveratrol (R), nicotine (N), and nicotine + resveratrol (NR). Rat dams of the N and NR offspring were exposed to nicotine (2 mg/kg/day) during pregnancy and lactation using a subcutaneously implanted minipump. The offspring of the R and NR groups received resveratrol (300 mg/kg of body weight, gavage) for 63 days from puberty. At 114 days of age, the male rats were euthanized. RESULTS: Nicotine did not alter the body weight, biometry of reproductive organs, or quantitative sperm parameters of adult offspring but caused an evident worsening of all sperm qualitative parameters studied. Daily treatment with resveratrol from puberty up to adulthood improved all qualitative sperm parameters significantly, leading some of them close to the control values. Resveratrol also improved the morphological integrity and expression of SIRT1 in the seminiferous epithelium of nicotine-exposed offspring. CONCLUSION AND DISCUSSION: Resveratrol reversed the male reproductive damage caused by nicotine. Nicotine crosses the blood-placental membrane and is present in the breast milk of mothers who smoke. Resveratrol restored the altered reproductive parameters in the male adult offspring that were nicotine-exposed during intrauterine life and breastfeeding. The epigenetic modulating action of resveratrol can be involved in this nicotine damage reversion. Resveratrol may be a promising candidate to be investigated regarding the adjuvant strategies in the treatment of male infertility.

Resveratrol benefits on sperm DNA, chromatin structure and reproductive outcomes of varicocelized rats.

In varicocele, the main cause of sperm DNA damage is oxidative stress (OS). Resveratrol, a polyphenol with antioxidant properties, can protect cells from injuries caused by OS. We investigated the benefits of resveratrol against reproductive damage caused by experimental varicocele induced from peripuberty. Eighty peripubertal male rats were distributed into 4 groups: sham-control (S), varicocele (V), resveratrol (R) and varicocele treated with resveratrol (VR). Varicocele was induced through the partial ligature of the left renal vein. Resveratrol was given in a daily dose of 300 mg/kg body weight (gavage). Sperm samples were collected at 100 days of age for vitality, DNA fragmentation and chromatin protamination evaluations. OS analyses were carried out. Rats from all groups were mated with healthy primiparous females for evaluation of reproductive capacity and embryonic quality. The V group showed reduction of sperm vitality, altered chromatin protamination and sperm DNA integrity and high levels of OS. The VR group showed an improvement of oxidative status, sperm vitality, DNA integrity and chromatin structure, and an enhancement in the gestational index and embryonic quality. Therefore, we showed in this experimental model that resveratrol is a promising nutraceutical adjuvant and should be deeply studied to mitigate subfertility in varicocele.