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.

Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty.

Carbamazepine (CBZ), an anticonvulsant drug, is used by pregnant women and crosses the placental barrier, reaching the embryo/foetus. CBZ inhibits testicular steroidogenesis and may lead to alterations in testicular development, spermatogenesis and male fertility. The purpose of this study was to evaluate the CBZ effects on testicular parameters in the neonatal and pubertal phases, as well as the spermatic parameters of pubertal rats, originated from dams treated during different periods of the pregnancy. Pregnant rats were treated with CBZ (20 mg/kg/day; intraperitoneal route), from 12-20 gestation day (GD) (CBZ12 group) and 15-20 GD (CBZ15 group). The testicular morphometric and stereological analysis of rats aged 4 and 63 days was performed. The oestradiol and testosterone plasmatic levels, as well as spermatic parameters, were achieved at 63 days. CBZ12 group showed a reduction in testicular weight and volume at 4 days post-partum (dpp); however, there was an increase in the seminiferous cords' length of the CBZ12 and CBZ15 groups. At 63 days, the CBZ12 group showed increases of the daily sperm production and damage in the seminiferous epithelium. The results suggest that CBZ interferes with the testis development and the establishment of the spermatogenic process, which can be detected in the puberty phase.

Histological and anatomical variations of septomarginal trabecula in bovine hearts.

The use of hearts from different animals as models in the experimental pharmacology and surgical clinic has led, in recent years, to an increase on interest of research with this organ. The heart's conducting system, from the septomarginal trabecula, presents several variations, which generates numerous controversies in the literature. So, the objective of the present study is to analyse the morphology of the septomarginal trabecula of bovine hearts, identifying possible macro- and microscopic variations. Thirty-four bovine hearts were analysed. Each trabecula was analysed macroscopically to obtain an anatomical description and measurements of its length and thickness. For histological and morphometric analysis, the samples were fixed in Bouin's solution and then subjected to histological processing. In all the analysed bovine hearts, the septomarginal trabecula presented itself as a smooth, tubular meaty structure of muscular consistency, with variable length and diameter. The anatomical variations observed included a trabecula with forked marginal fixation, and single septal fixation, in addition to a trabecula with extremely reduced or excessively thick caliber. The septomarginal trabecula consists of cardiac muscle fibres, connective tissue, vascular tissue and conduction myofibrils or Purkinje fibres. In the samples of smaller thicknesses, there was a predominance of connective tissue and scarce cardiac muscle tissue, whereas in the thicker samples the predominance was of cardiac striated muscle tissue. Therefore, there are significant macro- and microscopic differences between the bovine septomarginal trabecula concerning their diameter and constituent tissue, and that can lead to possible changes in cardiac physiology.

Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring.

Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells, affecting steroidogenesis and causes fetal malformation. The aim of this study was to investigate the effects of CBZ on male sexual maturation and other male parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding. The anogenital distance (AGD) and the anogenital index (AGI) were obtained. Testicular descent and preputial separation were also evaluated. The offspring was euthanized at PND 41 and 63. The accessory glands were weighed and the testes were collected for histopathological, morphometric and sterological analyses. The numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an increase of AGI and a delay of testicular descent and of preputial separation. CBZ also caused a decrease of testosterone level and of sperm count and an increase of abnormal sperm. These results indicate that CBZ delays puberty onset and affects steroidogenesis and sperm quality.

Carbamazepine damage to rat spermatogenesis in different sexual developmental phases.

Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also utilized for treatment of psychiatric disorders and neuropathic pain. The utilization of CBZ has been associated with damage to male reproduction including hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and long-term use of CBZ has been a common schedule for children and adolescents, despite the fact it alters the testosterone level in adult rats and humans. In addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and puberty is more susceptible to toxic agents than in adult phase. The objective of this work was to evaluate the side effects of CBZ on the spermatogenic process of rats from pre-puberty to puberty and sexual maturation. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and an increase in oestradiol levels were observed in rats, which were CBZ-treated since the weaning. The results suggest that CBZ, when administered from pre-puberty, provokes specific side effects on rat testes, resulting in more severe damage in the adult phase.