Infertility is increasingly recognized as being closely linked to obesity in humans. The successful production of fertile spermatozoa requires adequate spermatogenesis within the testis and proper spermatozoa maturation through the epididymis. This study aimed to evaluate the impact of body adiposity on male fertility, focusing on sperm parameters, epididymal sperm maturation, and sperm capacitation in Wistar rats. Male rats were randomized into three dietary groups over four weeks: a control group receiving less than 4% lard, regular chow, a 10% lard group, and a 60% lard group. Following dietary interventions, fertility tests were conducted across the groups. The epididymis was dissected into caput, corpus, and cauda regions to assess sperm concentration, vitality capacitation, carbohydrate distribution, tyrosine phosphorylation, and phosphatidylserine levels. Additionally, serum testosterone levels were measured to evaluate hormonal influences on fertility. The rats subjected to high-fat diets leading to overweight and obesity exhibited significant alterations in fertility. These changes were characterized by impaired epididymal sperm maturation, as evidenced by lower testosterone levels, decreased sperm viability, and capacitation. Furthermore, increased adiposity was associated with a lack of asymmetry in the plasma membrane, alteration in carbohydrate distribution, and changes in tyrosine phosphorylation. This study underscores the adverse effects of high-fat diets on male fertility, particularly through mechanisms affecting sperm maturation in the epididymis. The evidence suggests that obesity-induced alterations in sperm parameters and hormonal profiles may contribute to reduced fertility in male rats, which could have implications for understanding similar human processes.

Obesity is considered a metabolic disease, in which leptin is used as an indicator of energy in the body. This hormone, in turn, is related to the neuroendocrine regulation of the reproductive axis. However, leptin excess secretion due to obesity can have a negative effect on reproduction. Overweight and obesity were induced through high-calorie diets. Lee and gonadosomatic indices were determined to characterize the model and degree of reproductive development in the testis and epididymis. Sperm quality was analyzed using spermatobioscopy. Morphometry was analyzed through histological analysis. The changes described affect testicular function in hormone and sperm production. Exposure of 3-month-old male rats to diets with different fat contents (10% and 60%) induced both overweight and obesity. The animals showed morphological alterations, both testicular and epididymal, the latter being more sensitive to dietary changes by modifying the epididymal index, morphometric parameters (in both organs), and a decrease in cilia length. These changes induced a reduction in sperm viability, as well as an increase in malformed spermatozoa. In conclusion, both overweight and obesity have effects on male reproduction by modifying the morphology and physiology of reproductive organs.

Studies of adult depressed patients report that selective serotonin (5-HT) reuptake inhibitors (SSRIs) like clomipramine (CMI) have secondary effects on sperm quality. The epididymis possesses an autonomous serotonergic system critical for sperm maturation, whose establishment during neonatal development remains unexplored as a target for SSRI programming. We hypothesized that neonatal CMI exposure would disrupt the developing epididymal 5-HT system, leading to permanent sperm dysfunction. CMI (30 mg/kg s.c.) was administered to male rats between postnatal days 8–21. At 3 months, sperm from the epididymal cauda was evaluated, and 5-HT levels were measured in the testis, caput, and cauda epididymis. Our novel findings demonstrate that neonatal CMI exposure induces region-specific, long-term alterations in epididymal 5-HT levels (decreased in caput, increased in cauda) without affecting testicular 5-HT. This reprogramming of the local serotonergic milieu was associated with reduced sperm concentration, viability, normal morphology, and motility, alongside increased mitochondrial activity and reactive oxygen species. This study reveals, for the first time, that the epididymal serotonergic system is a key target for neonatal SSRI programming, providing a mechanistic link (altered 5-HT homeostasis) between early-life exposure and persistent sperm defects in adulthood.