1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA. Systematic review and meta-analysis. Not applicable. Couples with IRSA and their spontaneously aborted embryos. Summary odds ratios (ORs) were calculated by means of fixed- or random-effects models. Association of genetic variants with IRSA. The systematic review included 428 case-control studies (1990-2015), which differed substantially regarding RSA definition, clinical evaluation of patients, and selection of control subjects. In women, 472 variants in 187 genes were investigated. Meta-analyses were performed for 36 variants in 16 genes. Association with IRSA defined as three or more spontaneous abortions (SAs) was detected for 21 variants in genes involved in immune response (IFNG, IL10, KIR2DS2, KIR2DS3, KIR2DS4, MBL, TNF), coagulation (F2, F5, PAI-1, PROZ), metabolism (GSTT1, MTHFR), and angiogenesis (NOS3, VEGFA). However, ORs were modest (0.51-2.37), with moderate or weak epidemiologic credibility. Minor differences in summary ORs were detected between IRSA defined as two or more and as three or more SAs. Male partners were included in 12.1% of studies, and one study included spontaneously aborted embryos. Candidate gene studies show moderate associations with IRSA. Owing to large differences in RSA definition and selection criteria for participants, consensus is needed. Future GASs should include both partners and spontaneously aborted embryos. Genome-wide association studies and large-scale replications of identified associations are recommended.

Craniometric variation in humans reflects different genetic and environmental influences. Long-term climatic adaptation is less likely to show an impact on size and shape variation in a small local area than at the global level. The aim of this work was to assess the contribution of the particular environmental factors to body height and craniofacial variability in a small geographic area of Croatia. A total of 632 subjects, aged 18-21, participated in the survey. Body height, head length, head breadth, head height, head circumference, cephalic index, morphological face height, face breadth, and facial index were analysed regarding geographic, climatic and dietary conditions in different regions of the country, and correlated with the specific climatic variables (cumulative multiyear sunshine duration, cumulative multiyear average precipitation, multiyear average air temperatures) and calcium concentrations in drinking water. Significant differences between groups classified according to geographic, climatic or dietary affiliation, and the impact of the environmental predictors on the variation in the investigated traits were assessed using multiple forward stepwise regression analyses. Higher body height measures in both sexes were significantly correlated with Mediterranean diet type. Mediterranean diet type also contributed to higher head length and head circumference measures in females. Cephalic index values correlated to geographic regions in both sexes, showing an increase from southern to eastern Croatia. In the same direction, head length significantly decreased in males and head breadth increased in females. Mediterranean climate was associated with higher and narrower faces in females. The analysis of the particular climatic variables did not reveal a significant influence on body height in either sex. Concurrently, climatic features influenced all craniofacial traits in females and only head length and facial index in males. Mediterranean climate, characterized by higher average sunshine duration, higher average precipitation and higher average air temperatures, was associated with longer, higher and narrower skulls, higher head circumference, lower cephalic index, and higher and narrower faces (lower facial index). Calcium concentrations in drinking water did not correlate significantly with any dependent variable. A significant effect of environmental factors on body height and craniofacial variability was found in Croatian young adult population. This effect was more pronounced in females, revealing sex-specific craniofacial differentiation. However, the impact of environment was low and may explain only 1.0-7.32% variation of the investigated traits.

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.