Advanced age has been reported to negatively affect sperm parameters and spermatozoa DNA integrity. A decline in sperm criteria was also associated with altered epigenetic marks such as DNA methylation with a potential downstream impact on in vitro fertilization success and clinical outcomes. The aim of the present retrospective study was to clarify the association between advanced paternal age (APA) and sperm parameters, DNA integrity and DNA methylation profile. A total of 671 patients consulting for infertility underwent sperm analysis, sperm DNA integrity assessment and methylation level measurement. The principal finding was that individuals over 40 years of age exhibit a significant increase in DNA fragmentation levels compared to the younger group (15% versus 9%, respectively, p = 0.04). However, there was no significant difference in DNA decondensation and sperm parameters in association with APA. In addition, a drop in the global methylation level was also found in men over 40 years (6% in the young group versus 2% in the old group, p = 0.03). As a conclusion, men over 40 years are at higher risk of elevated sperm DNA fragmentation and lower methylation level. Based on these observations, it is recommended that the assessment of sperm DNA fragmentation should be taken into consideration particularly after the age of 40. Our findings support the idea that paternal age is a crucial factor that should not be neglected during fertility evaluation and treatment since it is associated with epigenetics changes in sperm. Although the underlying mechanism remains to be clarified, we believe that environmental and professional exposure factors are likely involved in the process.

The evaluation of sperm DNA integrity is recommended in the sixth edition of the 2021 World Health Organization guidelines. Oxidative stress has been identified as a crucial factor leading to genome decay, lipid peroxidation, and nucleoprotein oxidation. This double-blind, placebo-controlled clinical trial aimed to assess the effect of oral antioxidant treatment (Fertilis), which contains L-carnitine and some micronutrients, in the improvement of conventional sperm parameters, sperm DNA integrity and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. A total of 263 participants were enrolled and randomly divided into two groups: 131 participants received the antioxidant treatment, while 132 participants received a placebo. The male partners in both groups underwent the antioxidant treatment or the placebo for a duration of three months. For each participant, we performed a hormonal test, an infectious test, a spermogram, a TUNEL assay for sperm DNA fragmentation, a toluidine blue staining for sperm DNA decondensation, and an IVF/ICSI procedure. Sperm characteristics analysis (volume, count, motility, and vitality), sperm DNA fragmentation, and sperm DNA decondensation were assessed and compared to the results preceding the antioxidant treatment. The study outcome revealed a significant decrease in the DNA fragmentation index and a significant increase in sperm motility after 3 months of treatment (p = 0.01 and p = 0.02, respectively). Additionally, a significant improvement in clinical pregnancy rate (p = 0.01) and life birth rate (p = 0.031) was observed. No significant changes were observed in conventional sperm parameters (volume, count, and vitality) or sperm DNA decondensation (SDI). Antioxidant therapy has a beneficial impact on achieving pregnancy, whether through spontaneous conception or assisted reproductive procedures (ART).

Today, accumulating evidence highlights the impact of oxidative stress (OS) on semen quality. It is considered to be a key factor contributing to the decline in male fertility. OS is detected in 30–80% of men with infertility, highlighting its strong association with impaired reproductive function and with clinical outcomes following the use of assisted reproductive technologies. Spermatozoa are particularly vulnerable to oxidative damage due to their high content of polyunsaturated fatty acids (PUFAs) and limited antioxidant defense abilities. OS arises from an imbalance between the production of reactive oxygen species and the capacity to neutralize or repair their adverse effects. Evidence indicates that OS leads to lipid peroxidation, protein oxidation, mitochondrial dysfunction, and genomic instability. Micronutrient–antioxidant therapies can play a key role in infertility improvement by neutralizing free radicals and preventing cellular damage. Many different micronutrients, including L-carnitine, L-glutathione, coenzyme Q10, selenium, and zinc, as well as vitamins complexes, are proposed to improve sperm parameters and male fertility potential. This study aims to review the impact of antioxidant supplementation on semen parameters, including sperm volume, motility, concentration, morphology, genome integrity (maturity and fragmentation), and in vitro fertilization (IVF) outcomes. Antioxidant intake and a balanced lifestyle reduce oxidative stress and mitochondrial dysfunction, enhancing the spermatogenesis and spermiogenesis processes, improving sperm quality, and protecting DNA integrity.

Reproductive infertility is characterized by the inability to achieve pregnancy after a year or more of unprotected sexual intercourse. This review highlights the significant impact of exposure to both types of heavy metals (essential and non-essential) on the reproductive performance of various species, particularly humans. Heavy metals present a high atomic density and weight, including lead, mercury, cadmium, nickel, chromium, and arsenic, and are delivered into the environment through natural and human activities, posing a threat to ecological systems and human reproductive health. These heavy metals have the potential for bioaccumulation and can adversely affect male fertility and sperm quality due to their role in disrupting endocrine functions, altering hormone levels responsible for sperm production, and inducing oxidative stress. The elevated production of reactive oxygen species (ROS) exceeds the capability of antioxidants and can lead to the alteration of sperm quality. Seminal fluid contains antioxidants like vitamin C, vitamin E, zinc, and selenium to counteract the impacts of ROS and also to preserve the sperm function. This review aims also to explore the impact of heavy metals on sperm quality and their relationship with antioxidant imbalance and ROS. The exposure to heavy metals whether through occupational or environmental means increases the production of ROS and therefore leads to an imbalance of antioxidants production. All these factors have no doubt an impact on male reproductive health.

Emerging evidence has indicated the involvement of extrahypothalamic Kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) has an impact on the expression of Kisspeptin and GnRHR in the reproductive organs of rats’ offspring. A total of 16 pregnant rats are divided into four groups: a control group (n = 4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5.25 kcal/g HFD), and coexposed group (4 rats exposed to CPF and HDF). At postnatal development postnatal day (PND) 60, male and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed, and histological and immunohistological analysis and in silico quantification (TissueGnostics software 6.0.1.102, TissueFAXS, HistoQuest) were applied to investigate the impact of different treatments on Kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring’s body weight in the CPF group from PND30 and PND60 (p < 0.05 and p < 0.01, respectively). Histological analysis showed a significant increase in the atretic follicle and abnormal testis structure with germ cell desquamation in the CPF-exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and Kisspeptin in the HFD and CPF exposed groups, respectively, in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.