Bioconcentration of polycyclic aromatic hydrocarbons in the adipose tissue of women with pelvic endometriosis and idiopathic infertility: A case-control study.

PURPOSE: Polycyclic aromatic hydrocarbons (PAHs), present in air and food, generated during energy production and waste incineration, are known for health toxicity. PAHs may activate the aryl hydrocarbon receptor, which could in turn modify estrogen-dependent inflammatory pathways in endometriosis. The possible role of PAHs in the pathogenesis of endometriosis remains unclear. The study aimed to evaluate the potential link between exposure to PAHs and the occurrence of peritoneal and ovarian endometriosis. METHODS: A prospective case-control tertiary-center study included 46 women aged 22-45 undergoing laparoscopy due to pelvic endometriosis (n â€‹= â€‹32; arm 1) and idiopathic infertility (n â€‹= â€‹14; arm 2). A sample of the greater omentum was collected intraoperatively for detection of 16 standard PAHs by gas chromatography-isotope dilution mass spectrometry method. PAHs concentrations were compared in both study arms. The associations between PAHs concentrations and selected variables were investigated. RESULTS: There were no significant differences between both arms in terms of reference PAHs concentrations, nor correlations between PAHs concentrations and the stage of endometriosis. However, notable differences were observed in specific PAHs concentrations related to certain conditions. The concentrations of acenaphthene (p â€‹= â€‹0.016) and fluorene (p â€‹= â€‹0.013) were significantly lower in women with peritoneal adhesions, while the concentrations of benz[a]anthracene, benzo[k]fluoranthene and indeno[1,2,3-cd]pyrene [ng/g] were higher in cigarette smokers. CONCLUSIONS: The study showed no differences in exposure to PAHs between women with and without pelvic endometriosis. Determining the toxicity of PAHs in endometriosis requires further research.

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence.

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.

Combination clomiphene citrate and anastrozole duotherapy improves semen parameters in a multi-institutional, retrospective cohort of infertile men.

In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective aromatase inhibitor, are often employed. The effects of jointly administering these agents on semen parameters are not well understood. Here, we describe the findings of our multi-center, retrospective cohort study of men with idiopathic primary or secondary infertility. Twenty-one men were treated with combination therapy (anastrozole and clomiphene) and 69 men were treated with monotherapy (anastrozole). Patients with pre-treatment normozoospermia and recent or current exogenous testosterone therapy were excluded. Baseline and post-treatment semen and sex hormone parameters were compared among groups. The median follow-up duration was 91 days [interquartile range (IQR), 64-117 days]. Following treatment, 43% of men in the combination therapy group demonstrated normozoospermia, compared to 25% in the monotherapy group. Furthermore, men in the combined group demonstrated marked improvements in total motile sperm count (TMSC) [11.3 vs. 2.1 million (M), P=0.03]. There were no significant differences in hormone levels among the two groups following treatment. Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment semen parameters, when compared to anastrozole monotherapy. These benefits may contribute to improvements in pregnancy outcomes with less invasive assisted reproductive technologies, such as intrauterine insemination (IUI). Future investigations with larger sample sizes and prospective study designs are necessary.

Seminal Oxidative Stress and Sperm DNA Fragmentation in Men from Couples with Infertility or Unexplained Recurrent Pregnancy Loss.

(1) Background: This case-control study examined whether men from couples with unexplained recurrent pregnancy loss (RPL) or infertility exhibited higher seminal oxidative stress (OS) and sperm DNA fragmentation (SDF) compared to fertile controls. (2) Methods: The study included 30 participants from each group: unexplained RPL, unexplained infertility, and proven fertility. Data were collected at Aalborg University Hospital tertiary RPL and fertility treatment clinics (Aalborg, Denmark), excluding couples with mixed conditions for homogeneity. Semen samples were analyzed using computer-aided sperm analysis (CASA) for concentration, motility, and morphology. SDF was assessed via a CASA-based sperm chromatin dispersion test. OS was measured as static oxidation-reduction potential (sORP). (3) Results: The results showed no significant OS differences between groups. The RPL group had significantly lower SDF levels than the control group. A significant positive correlation between SDF and OS was observed in the infertility group. Overall, this study did not find significant differences in OS levels between men from couples with unexplained RPL or infertility and fertile controls, while SDF levels were lower in the RPL group compared to controls. (4) Conclusion: In conclusion, despite the existing literature suggesting that OS and SDF are negative prognostic factors, our findings suggest they may not be reliable diagnostic markers for RPL and infertility.

Role of vaginal microbiota in idiopathic infertility: a prospective study.

OBJECTIVE: The causes of idiopathic infertility are still not known; however, it may be associated with microbial etiologies. The present study examines the vaginal microbiota of infertile as well as fertile women longitudinally. METHODOLOGY: The study was presented and accepted by the Institutional Ethical Committee of Shri Mata Vaishno Devi University, Katra, Jammu and Kashmir (India). An observational, prospective, multicenteric investigation was conducted at the Department of Obstetrics and Gynecology, Government Medical College Jammu, and its affiliated hospitals in Jammu and Kashmir (India). In order to examine the microbial composition, a cohort of 80 female individuals were involved in the screening process. The investigation involved sequencing of the V3-V4 region of 16S rRNA gene, which was subsequently analyzed using the Mothur pipeline. RESULTS: The study revealed that the vaginal microbiota of infertile women differed from that of healthy women who had previously given birth without any complications. Both populations have variations in their alpha as well as beta diversity and taxonomical composition. The microbial profiles in the cases of infertility are characterized by elevated levels of Gardnerella, Prevotella, Atopobium, and Enterococcus whereas a higher level of Lactobacillus iners was observed in case of fertile women. CONCLUSION: In conclusion, it can be inferred that the composition of the vaginal microbiome potentially exerts a significant influence on females afflicted with idiopathic infertility.

Combined evaluation of prolactin-induced peptide (PIP) and extracellular signal-regulated kinase (ERK) as new sperm biomarkers of FSH treatment efficacy in normogonadotropic idiopathic infertile men.

PURPOSE: Nearly, 40% of the causes of male infertility remain idiopathic. The only suggested treatment in idiopathic oligo- and/or asthenozoospermia in normogonadotropic patients is the FSH. In the current clinical practice, efficacy is exclusively assessable through semen analysis after 3 months of treatment. No molecular markers of treatment efficacy are appliable in clinical practice. The aim of the present work is to evaluate the combination of extracellular signal regulated kinase (ERK) 1 and 2 and prolactin inducible peptide (PIP) as potential markers of idiopathic infertility and FSH treatment efficacy. METHODS: Western blot and confocal microscopy were performed to analyze the modulation of PIP and ERK1/2 in idiopathic infertile patients (IIP) sperm cells. Taking advantage of mass spectrometry analysis, we identified these proteins unequivocally in sperm cells. RESULTS:  We demonstrated a significant decrease of both PIP protein and of ERK1/2 levels in spermatozoa obtained from IIP in comparison to healthy fertile patients (HFP). Conversely, we reported a significant increase of these markers comparing infertile patients before and after 3 months of FSH treatment. Importantly, this correlated with an increase in total number of sperm and sperm motility after FSH treatment. Finally, we identified of PIP and ERK2 proteins in sperm samples by proteomic analysis. CONCLUSIONS: The combined evaluation of ERK1/2 and PIP proteins might represent a useful molecular marker to tailor FSH treatment in the management of male normogonadotropic idiopathic infertility.

Etiology of Male Infertility: an Update.

Spermatogenesis is a complex process of germ cell division and differentiation that involves extensive cross-talk between the developing germ cells and the somatic testicular cells. Defective endocrine signaling and/or intrinsic defects within the testes can adversely affect spermatogenic progression, leading to subfertility/infertility. In recent years, male infertility has been recognized as a global public health concern, and research over the last few decades has elucidated the complex etiology of male infertility. Congenital reproductive abnormalities, genetic mutations, and endocrine/metabolic dysfunction have been demonstrated to be involved in infertility/subfertility in males. Furthermore, acquired factors like exposure to environmental toxicants and lifestyle-related disorders such as illicit use of psychoactive drugs have been shown to adversely affect spermatogenesis. Despite the large body of available scientific literature on the etiology of male infertility, a substantial proportion of infertility cases are idiopathic in nature, with no known cause. The inability to treat such idiopathic cases stems from poor knowledge about the complex regulation of spermatogenesis. Emerging scientific evidence indicates that defective functioning of testicular Sertoli cells (Sc) may be an underlying cause of infertility/subfertility in males. Sc plays an indispensable role in regulating spermatogenesis, and impaired functional maturation of Sc has been shown to affect fertility in animal models as well as humans, suggesting abnormal Sc as a potential underlying cause of reproductive insufficiency/failure in such cases of unexplained infertility. This review summarizes the major causes of infertility/subfertility in males, with an emphasis on infertility due to dysregulated Sc function.

Single nucleotide polymorphism rs527236194 of the cytochrome B gene (MT-CYB) is associated with alterations in sperm parameters.

BACKGROUND: The mitochondrial genome is substantially susceptible to mutations and has high polymorphism due to structural features, location, and lack of recombinant variability, as its inheritance is strictly maternal. All of these events can be accompanied by the accumulation of mitochondrial single nucleotide polymorphisms (mtSNPs) in the sperm. The aim of this research was to analyze the influence of mutations in the MT-CYB gene on sperm quality. METHODS AND RESULTS: We conducted a case‒control study to identify mutations in the mitochondrial cytochrome B (MT-CYB) gene in men with asthenoteratozoospermia (89 cases) and oligoasthenoteratozoospermia (65 cases). The comparison group consisted of 164 fertile men. Somatic cell lysis followed by mtDNA extraction was conducted to analyze three mtDNA polymorphisms, rs28357373 (T15629C (Leu295=), rs527236194 (T15784C (p.Pro346=), rs2853506 (A15218G, p.Thr158Ala). Detection and genotyping of polymorphic loci in the MT-CYB gene was performed using the TaqMan allelic discrimination assay. To verify mutations in the MT-CYB gene, automated Sanger DNA sequencing was used. We found that rs527236194 was associated with asthenoteratozoospermia. rs28357373 in the MT-CYB gene did not show any polymorphism in the analyzed groups, which indicates a rare frequency of the TT genotype in our region. Rs28357373 and rs2853506 are not associated with male sperm abnormalities in the Volga-Ural region. CONCLUSION: The association of the rs527236194 polymorphic variant with sperm parameter alterations suggests its role in the pathophysiology of male infertility and requires further investigation in larger samples.

Sperm Concentration Improvement May Be a Parameter Predicting Efficacy of FSH Therapy of Male Idiopathic Infertility.

Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 ± 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 - 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration < 7.3 mill/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number.

The cost-effectiveness of using a prognosis-tailored strategy model to triage couples with idiopathic infertility for assisted reproduction technology.

OBJECTIVES: To evaluate whether a prognosis-tailored triage of ART for couples with idiopathic infertility by using the Hunault prognostic model can decrease the cost of treatment without compromising the chance of live birth. STUDY DESIGN: This is a retrospective study conducted in an Australian fertility clinic. Couples seeking infertility consultation who were subsequently found to have idiopathic infertility after evaluation were included. We compared the costs per conception leading to live birth of the prognosis-tailored strategy with the immediate ART strategy, which generally reflects the current practice in Australian fertility clinics, over a 24-month period. In the prognosis-tailored strategy, for each couple, the prognosis for natural conception was assessed using the well-established Hunault model. Total cost of treatments were calculated as the sum of typical out-of-pocket and Australian Medicare cost (Australian national insurance scheme). RESULTS: We studied 261 couples. In the prognosis-tailored strategy, the total cost was $2,766,781 and the live birth rate was 63.9%. In contrast, the immediate ART strategy yielded a live birth rate of 64.4% with a total cost of $3,176,845. Implementing the prognosis-tailored strategy using the Hunault model saved $410,064 in total and $1,571 per couple. The incremental cost-effectiveness ratio (ICER) was $341,720 per live birth. CONCLUSION: In couples with idiopathic infertility, assessment of prognosis for natural conception using the Hunault model and delaying ART for 12 months in couples with favourable prognoses can considerably reduce costs without significantly compromising live birth rates.

Follicular Fluid Components in Reduced Ovarian Reserve, Endometriosis, and Idiopathic Infertility.

Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F2-Isoprostanes (F2-IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F2-IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-Müllerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions.

The therapeutic effect of co-administration of pentoxifylline and zinc in men with idiopathic infertility.

Pentoxifylline is a derivative of methylxanthine that affects sperm motility. Also, zinc is an antioxidant that is involved in the activation of antioxidant enzymes. This study aimed to evaluate the effect of co-administration of pentoxifylline, and zinc in men with idiopathic infertility. In the present study, men with idiopathic infertility were identified and randomly divided into four groups: pentoxifylline, zinc, pentoxifylline + zinc, and placebo. According to the grouping, the patients received pentoxifylline and zinc for 3 months. Then, sperm parameters, biochemical factors, reproductive hormones, inflammatory factors, and DNA damage were evaluated before and after intervention. Data analysis was performed using SPSS software. Pentoxifylline and zinc were significantly effective in improving biochemical parameters, inflammatory factors, concentration, and motility of sperm. Pentoxifylline did not affect sperm morphology and reproductive hormones. However, in the zinc and zinc + pentoxifylline groups, a significant increase in normal morphology and reproductive hormones was observed. In the pentoxifylline group, sperm DNA fragmentation increased significantly, while in the zinc and zinc + pentoxifylline group, DNA fragmentation reduced significantly. Because of the role of zinc in protecting sperm chromatin, it is recommended that zinc and pentoxifyllinebe prescribed simultaneously. Clinical trial code: NCT05156684.

Aberrant Mannosylated and Highly Fucosylated Glycoepitopes of Prostatic Acid Phosphatase as Potential Ligands for Dendritic-Cell Specific ICAM-Grabbing Nonintegrin (DC-SIGN) in Human Seminal Plasma-A Step towards Explaining Idiopathic Infertility.

Semen prostatic acid phosphatase (PAP) has been proposed as an endogenous ligand for dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), which plays a critical immuno-modulating role in maintaining homeostasis in the female reproductive tracts. In the current study, we assumed that semen PAP bears a set of fucosylated and mannosylated glycans, which may mediate the efficient binding of PAP to DC-SIGN. To investigate this hypothesis, we developed ELISA assays using Galanthus nivalis and Lotus tetragonolobus lectins capable of binding mannose-containing glycans or LewisX and LewisY motifs, respectively. In our assay with Galanthus nivalis, we detected that the relative reactivity of PAP mannose-presenting glycans in the normozoospermic idiopathic group was significantly higher than in the asthenozoospermic, oligozoospermic and oligoasthenozoospermic groups. Simultaneously, we observed slight differences in the relative reactivities of PAP glycans with Lotus tetragonolobus lectin among groups of patients with abnormal semen parameters. Subsequently, we examined whether DC-SIGN interacts with seminal plasma PAP glycans, and we detected a significantly higher relative reactivity in the normozoospermic group compared to the oligozoospermic group. Finally, we concluded that the significantly aberrant abundance of mannosylated functional groups of PAP among patients with semen disorders can suggest that PAP may thereby be engaged in modulating the immune response and promoting a tolerogenic response to male antigens in the female reproductive system.

ß-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility.

Sperm chemotaxis is required for guiding sperm toward the egg. However, the molecular identity of physiological chemoattractant and its involvement in infertility remain elusive. Here, we identify DEFB19/119 (mouse/human orthologs) as a physiological sperm chemoattractant. The epithelia of the female reproductive tract and the cumulus-oocyte complex secrete DEFB19/119 that elicits calcium mobilization via the CatSper channel and induces sperm chemotaxis in capacitated sperm. Manipulating the level of DEFB19 in mice determines the number of sperm arriving at the fertilization site. Importantly, we identify exon mutations in the DEFB119 gene in idiopathic infertile women with low level of DEFB119 in the follicular fluid. The level of DEFB119 correlates with the chemotactic potency of follicular fluid and predicts the infertile outcome with positive correlation. This study reveals the pivotal role of DEFB19/119 in sperm chemotaxis and demonstrates its potential application in the diagnosis of idiopathic infertility.

The role of macrophages in reproductive-related diseases.

The study of reproductive immunology includes the role of immunity in reproductive physiology and reproductive-related diseases. Reproductive-related diseases cause low pregnancy rate mainly through ovulation disorders, low-quality sperm production, embryo implantation failure and pregnancy maintenance disorders. Numerous cell types including infiltrating immune cells perform specific functions in the reproductive system. Physiologically macrophages are enriched in the decidua and testes, and macrophages are involved in endometrial receptivity, embryo implantation and spermatogenesis. Pathologically macrophages are associated with alterations of decidual microenvironment in recurrent implantation failure (RIF) and unexplained recurrent miscarriage (uRM), local inflammation in polycystic ovary syndrome (PCOS) and clearance of endometriotic lesions in endometriosis. Although researchers have recently attempted to uncover the pathogenesis and provide effective treatments for the reproductive-related diseases, the specific mechanisms and effective therapies need to be further explored. Here we summarized the latest mechanisms by which macrophages participate in the progression of the reproductive-related diseases, and the promising immune-based treatments. In addition, we discussed decidual macrophage classification and the importance of immune networks in reproduction-related diseases.

The Effect of the Time Interval From Sperm Processing to Intrauterine Insemination on the Pregnancy Outcomes of Infertile Women.

Objective: Intrauterine insemination (IUI) is the first-line treatment in couples suffering from various causes of subfertility and infertility. Considering the relatively low rate of pregnancy achieved with each cycle in this method, optimizing various steps in the process including the time interval from sperm collection to IUI may result in an increased rate of success. The goal of this study was to assess the impact of time intervals from the end of sperm processing to IUI (SP-IUI) on the pregnancy rate in IUI. Materials and methods: This single-center prospective cohort study evaluated couples with normal male partner sperm analysis and idiopathic female infertility undergoing IUI from 2018 to 2021. Cycles were stimulated using subcutaneous recombinant FSH and oral Letrozole. Ovulation was triggered using GnRH antagonist when the leading follicle's size reached greater than 14mm. The participants were placed in one of the three groups based on SP-IUI: group 1 (0-60 min), group II (60-90 min), and Group III: (>90 min). Results: 269 couples were included in the study. Sperm processing expectedly resulted in an increased concentration of total sperm count and sperm motility (P<0.001). The rate of chemical or clinical pregnancy, abortion, IUFD, multigestation, pregnancy, term birth, and ectopic pregnancy was not significantly different across study groups (P>0.05). Conclusion: The results of this study suggest that SP-IUI intervals evaluated in this study do not vary in terms of pregnancy rate or adverse pregnancy outcomes in IUI with normal male partner semen analysis. Hence, infertile couples can be flexible in the collection of semen specimens without time and site (at home or hospital) limitations.

Identification of potential key genes related to idiopathic male infertility using RNA-sequencing data: an in-silico approach.

Among reproductive health problems, idiopathic infertility affects married couples. The current diagnosis of male infertility focuses on the concentration, motility, and morphology of sperm in the ejaculate. Since the molecular mechanism of idiopathic infertility is unknown, identification of Differentially Expressed Genes (DEGs) among the control and idiopathic infertile male can shed light on diagnosis and treatment. Here, we analyzed the dataset GSE65683 to identify DEGs in idiopathic human sperm in three groups of patients: (i) Timed Intercourse (TIC); (ii) Intrauterine Insemination (IUI); and (iii) Assisted Reproductive Technology (ART). The enrichment analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and GeneCodis for the DEGs. Protein-Protein Interaction (PPI) network of these DEGs were constructed using the STRING database. The network parameters such as degree and betweenness were calculated to select the important hubs. In total, 118 DEGs in TIC, 446 in IUI, and 188 in ART were identified. PPI network was constructed and identified critical top hub genes such as ACTB, BTBD6, EIF2S3, EIF3A, EIF4E, POLR2L, RPL4, RPL7, RPS11, RPL13, RPS15, RPL23, RPL27, RPL9, RPLP0 and UBA52 that may play an essential role in idiopathic male infertility. Thus, the identified hub genes may provide an insight into the molecular mechanism and contribute to discovering novel therapeutic targets and developing new strategies for idiopathic male infertility.

Effect of Bisphenol S on testicular tissue after low-dose lactation exposure.

Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Lactating dams were exposed to BPS through drinking water (0.216 ng g bw/day and 21.6 ng g bw/day) from post-natal day 0-15. Although there was no significant difference in testicular histopathology between the control and experimental groups, we observed an increase in the number of tight and gap junctions in the blood-testis barrier (BTB) of adult mice after lactation BPS exposure. Moreover, there was an increase in oxidative stress markers in adult testicular tissue of mice exposed via breast milk. Our lactation model indicates that breast milk is a route of exposure to an endocrine disruptor that can be responsible for idiopathic male infertility through the damage of the BTB and weakening of oxidative stress resistance in adulthood.