Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in infertility, with a focus on DNA methylation, histone modification, and non-coding RNAs. We investigate the specific epigenetic events that occur during gametogenesis, with a focus on spermatogenesis and oogenesis as distinct processes. Furthermore, we investigate how environmental factors such as diet, stress, and toxin exposure can influence these epigenetic changes, potentially leading to infertility. The second part of the review explores epigenetic changes as therapeutic targets for infertility. Emerging therapies that modulate epigenetic marks present promising opportunities for fertility restoration, particularly in spermatogenesis. By summarizing current research findings, this review emphasizes the importance of understanding epigenetic contributions to infertility. Our discussion aims to lay the groundwork for future research directions and clinical applications in reproductive health.

Epigenetic biomarkers, such as DNA methylation, histone alterations, and non-coding RNAs, are increasingly recognized as essential instruments in disease diagnoses, prognostics, and customized therapy. As their clinical significance increases, so does the necessity for robust, interpretable, and scalable techniques that can accurately detect these molecular alterations. This review provides a critical and organized overview of contemporary technologies employed to characterize the principal categories of epigenetic modifications, encompassing PCR- and sequencing-based methods, high-resolution immunoprecipitation techniques, and CRISPR-enhanced detection systems. Although numerous procedures are technically well-established, their implementation outside research laboratories frequently faces substantial challenges: elevated prices, data intricacy, absence of standardization, and restricted translational frameworks. Furthermore, the interpretation of epigenetic data continues to pose a significant difficulty, especially for heterogeneous clinical samples and the swiftly advancing computational techniques. We examine the advantages and drawbacks of existing approaches, focusing on their incorporation into biomedical engineering platforms, including biosensors, lab-on-a-chip devices, and AI-assisted diagnostics. This review seeks to assist researchers, physicians, and engineers in choosing suitable technologies, comprehending their limitations, and pinpointing areas requiring urgent innovation by merging analytical rigor with a pragmatic viewpoint.

Background and Objectives: Preterm birth (PTB) is a complex condition with various contributing factors, including genetic and epigenetic influences such as DNA methylation. Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in DNA methylation and the remethylation of homocysteine. This study aimed to investigate the association between maternal MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation levels, and the risk of idiopathic spontaneous preterm birth (SPTB) in Caucasian women from Croatia and Slovenia. Materials and Methods: A total of 50 women with SPTB (<34 weeks of gestation) and 50 control women were included in the study. MTHFR polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and LINE-1 DNA methylation levels were quantified using the MethyLight method. Results: The study found no significant differences in MTHFR C677T and A1298C polymorphisms’ genotype or allele frequencies between women with SPTB and controls. Additionally, no statistical significance of LINE-1 DNA methylation was found between the genotypes of the MTHFR polymorphisms analyzed. Conclusions: The study suggests no conclusive association between MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation, and SPTB in Croatian and Slovenian women. Considering prior evidence connecting MTHFR polymorphisms, hyperhomocysteinemia, and PTB, the lack of homocysteine measurements and unassessed impact of folate or vitamin B supplementation limit the conclusions.

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed.

Reciprocal translocation is a chromosomal aberration where fragments are exchanged between two non-homologous chromosomes. Its prevalence is estimated at 0.16–0.2 % in the general population, rising to 1.3 % among infertile men. We report a 34-year-old Caucasian male with asthenozoospermia who was admitted for genetic testing. G-banding revealed a reciprocal translocation between chromosomes 12 and 15, with a karyotype of 46,XY,t(12;15)(p13.2?q15). Fluorescence in situ hybridisation confirmed this translocation using specific probes for chromosomes 12 and 15. This case highlights a rare chromosomal translocation t (12; 15) (p13.2? q15) associated with asthenozoospermia. Further sequencing analysis is needed to determine the precise breakpoints and assess potential genotype-phenotype correlations.

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks’ gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks’ gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3–4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively.