Effect of Micronutrients and L-Carnitine as Antioxidant on Sperm Parameters, Genome Integrity, and ICSI Outcomes: Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

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).

Endocrine disrupting chemicals and male fertility: from physiological to molecular effects.

The deleterious effects of chemical or non-chemical endocrine disruptors (EDs) on male fertility potential is well documented but still not fully elucidated. For example, the detection of industrial chemicals' metabolites in seminal plasma and follicular fluid can affect efficiency of the gametogenesis, the maturation and competency of gametes and has guided scientists to hypothesize that endocrine disrupting chemicals (EDCs) may disrupt hormonal homoeostasis by leading to a wide range of hormonal control impairments. The effects of EDCs exposure on reproductive health are highly dependent on factors including the type of EDCs, the duration of exposure, individual susceptibility, and the presence of other co-factors. Research and scientists continue to study these complex interactions. The aim of this review is to summarize the literature to better understand the potential reproductive health risks of EDCs in France.

Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs.

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.

Paternal Age Matters: Association with Sperm Criteria's- Spermatozoa DNA Integrity and Methylation Profile.

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.

Effect of pesticide exposure on human sperm characteristics, genome integrity, and methylation profile analysis.

According to the United Nations' Food and Agriculture Organization, the quantities of pesticide used around the world have increased regularly since the 1990s. Given that pesticides may be classified as carcinogenic, mutagenic, neurotoxic, or toxic for reproduction, some have endocrine-disrupting properties that might be associated with a decline in sperm parameters in general and sperm DNA integrity in particular. These days, a sperm analysis is not enough to determine the etiology of male infertility. Genome integrity analysis is a key step in clarifying a large proportion of cases of male infertility. The objective of the present retrospective study was to assess the impact of self-reported pesticide exposure on sperm parameters and sperm DNA integrity in men consulting for infertility. In a retrospective study, a population of 671 men living in the Picardy region of France were assessed in a conventional sperm parameter analysis, Shorr staining, a DNA fragmentation assay (terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling), and chromatin decondensation with aniline blue staining. The exposed and the non-exposed groups did not differ significantly in some of the conventional sperm parameters (including volume, sperm count, and percent typical forms). However, vitality, progressive motility, and non-progressive motility were significantly lower in the exposed group. Levels of DNA fragmentation and chromatin decondensation were moderately higher in the exposed group.

Impact of Pesticide Residues on the Gut-Microbiota-Blood-Brain Barrier Axis: A Narrative Review.

Accumulating evidence indicates that chronic exposure to a low level of pesticides found in diet affects the human gut-microbiota-blood-brain barrier (BBB) axis. This axis describes the physiological and bidirectional connection between the microbiota, the intestinal barrier (IB), and the BBB. Preclinical observations reported a gut microbial alteration induced by pesticides, also known as dysbiosis, a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs, such as the BBB. However, the interplay between pesticides, microbiota, the IB, and the BBB is still not fully explored. In this review, we first consider the similarities/differences between these two physiological barriers and the different pathways that link the gut microbiota and the BBB to better understand the dialogue between bacteria and the brain. We then discuss the effects of chronic oral pesticide exposure on the gut-microbiota-BBB axis and raise awareness of the danger of chronic exposure, especially during the perinatal period (pregnant women and offspring).

Effect of intrauterine administration of human chorionic gonadotropin one day before fresh blastocyst transfer on clinical outcomes: a quasi-experimental study.

Introduction: embryo implantation is a crucial step for assisted reproductive technology (ART) achievement. Human chorionic gonadotropin (hCG) is one of the main regulators of the implantation process. Studies focusing on the impact of intrauterine hCG infusion at the time of embryo transfer on clinical ART outcomes have shown controversial results, mainly at blastocyst stage. In this study, we aimed to investigate whether intrauterine hCG infusion one day before human blastocyst transfer in fresh invitro fertilization (IVF) cycles enhances implantation and pregnancy rates. Methods: a total of 174 subfertile women undergoing autologous fresh blastocyst transfer were enrolled in this randomized prospective study. Patients were randomly divided into three groups; group 1 (n = 54) and group 2 (n = 59) received an intrauterine injection of respectively 500 IU and 1000 IU of hCG one day before blastocyst transfer and the control group (n= 61) did not receive any intrauterine injection. The pregnancy and implantation rates were compared between the three study groups. Results: significant difference was found between the study groups. The bio chemical pregnancy rates were 25.9%, 30.5% and 29.5%, the clinical pregnancy rates were 24.1%, 27.1% and 27.9% and the implantation rates were 14.9%, 17.9% and 18.7% respectively in group 1,2 and control group. Conclusion: our results have shown that clinical outcomes in fresh IVF cycles cannot be improved through intrauterine hCG administration one day prior to blastocyst transfer, neither with 500 IU of hCG nor with a higher dose of 1000 IU of hCG.