Factors affecting clinical manifestation of chromosomal imbalance in carriers of segmental autosomal mosaicism: differential impact of gender

Mosaicism for unbalanced chromosomal rearrangements segmental mosaicism (SM) is rare, both in patients referred for cytogenetic testing and in prenatal diagnoses. In contrast, in preimplantation embryos SM is a frequent finding and, therefore, is even more challenging. However, there is no consistency among results of published studies on the clinical outcomes of embryos with SM, primarily due to the small number of reported cases. Moreover, there is the problem of predicting the potential for the optimal development of a mosaic embryo to a healthy individual. Therefore, we suggested comparing factors predisposing to favorable and poor prognoses, identified in postnatal and prenatal cohorts of SM carriers, with those obtained from studies on preimplantation embryos. We analyzed 580 published cases of SM including (i) postnatally diagnosed affected carriers, (ii) clinically asymptomatic carriers, (iii) prenatally diagnosed carriers, and (iv) miscarriages. We observed a concordance with preimplantation diagnoses regarding the clinical significance of the extent of mosaicism as well as a predominance of deletions over other types of rearrangements. However, there is no concordance regarding excessive involvement of chromosomes 1, 5, and 9 in unbalanced rearrangements and a preferential involvement of larger chromosomes compared to short ones. Paternal age was not found to be associated with SM in postnatally disease-defined individuals. We have identified maternal age and preferential involvement of chromosome 18 in rearrangements associated with clinical manifestations. Male predominance was found among normal pregnancy outcomes and among disease-defined carriers of rearrangements resulting in a gain of genomic material. Female predominance was found among abnormal pregnancy outcomes, among disease-defined carriers of loss and gain/loss rearrangements, and among transmitting carriers of gonadal SM, both affected and asymptomatic. According to data obtained from “post-embryo” studies, clinical manifestations of chromosomal imbalance are associated with a high proportion of abnormal cells, female gender, the type of rearrangement and involved chromosome(s), and maternal age. We believe these data are instructive in the challenging medical genetic counseling of parents faced with no option other than transfer of an embryo with segmental mosaicism.

Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973–2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32–36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.12] and sibling analyses (HR 1.10, 95% CI 1.02–1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

Male fertility: a review of the publications July — September 2021

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published according to the SCImago Journal Rank (SJR). As a result, we formed a list of 10 articles published in the III quarter (July — September) of 2021. The review included articles concerning the following issues: the ability of oocytes to repair damaged DNA-chains of sperm cells, the effectiveness of ICSI in AZF-c microdeletions, the advanced paternal age, artificial intelligence in reproductive clinics, genetic causes of infertility, the effect of surgical treatment of varicocele concerning DNA fragmentation, the role of ICSI in the frequency of chromosomal abnormalities in offspring, the safety of COVID-19 vaccination for spermatogenesis, as well as the novel WHO 6 manual for semen investigation.

Genetic, parental and lifestyle factors influence telomere length

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1,046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Coupling these measurements to single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.

Association of Voluntary Legal Paternity and Breastfeeding Duration and Exclusivity in a Sample of Mothers in NewYork State, United States

Background and Objective: Globally, father engagement is deemed an important factor in mothers’ breastfeeding practices. In the U.S., the role of the father in breastfeeding is understudied. This study examines the association between voluntary legal paternity and maternal breastfeeding outcomes. Methods: Using data from a modified Pregnancy Risk Assessment Monitoring System survey (Monroe County, NY, 2015-2017) linked to New York State’s birth certificate data, we assessed breastfeeding outcomes (exclusivity and duration) by voluntary legal paternity (VLP) establishment. We examined breastfeeding duration (breastfeeding cessation at 13 weeks or less) and exclusive breastfeeding (at 13 weeks) among mothers whose infants had VLP (i.e., married, acknowledgment at birth), and those who had no-VLP (i.e., a court-mandated Paternity Affidavit or no legal paternity established). Univariate analyses were conducted, with additional variables (parental demographics, maternal social and clinical) included subsequently. The backward elimination method was used to determine the set of covariates to adjust in the model. Results: Of the 1,753 mothers initiating breastfeeding, 1,364 had VLP and 389 had no-VLP established. Mothers of infants with a no-VLP were more likely to be Black (29.49%), Hispanic (17.74%), have lower income (80.21%), have lower-education levels (44.73%) and were more likely to be <30 years old (61.7%), and had higher levels (14.4%) of reported traumatic stress before and during the most recent pregnancy. Among mothers initiating breastfeeding, those with no-VLP had a higher risk of breastfeeding cessation at 13 weeks (OR: 2.06; 95% CI, 1.25-3.42) after adjusting for maternal resilience, social support, hospital breastfeeding support, pre-pregnancy BMI, paternal age, and paternal education; and higher risk of breastfeeding cessation at 13 weeks (OR:1.46; 1.01-2.09). Conclusion and Implications for Translation: Voluntary legal establishment of paternity is associated with maternal breastfeeding outcomes. Screening of mothers may include legal paternity status as a further indication of the need for additional breastfeeding support, especially among socio-economically disadvantaged populations. Copyright © 2021 Alio et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

A Review on Male Infertility - Environmental Factors, Pathophysiological and Oxidative Stress

Male infertility is one of the rising global problems with an increasing decline in male semen quality among men living in Asia, Europe, Africa and North America. Infertility is defined as the failure of conception after at least 12 months of unprotected intercourse. Globally 70 million people are affected by infertility. Environmental, occupational and modifiable lifestyle factors may contribute to this decline of male fertility. Various factors associated with male infertility include smoking cigarettes, alcohol intake, use of illicit drugs, obesity, genetic factors, heavy metals, psychological stress, exposure to pesticides and industrial chemicals, poor nutrition intake, oxidative stress, sedentary lifestyle, advanced paternal age, diet and coffee consumption. KEY WORDS Infertility, Antioxidant, Environmental Factors, Endocrine Factors