Paternal Inheritance Research Articles

Reassessing Banana Phylogeny and Organelle Inheritance Modes Using Genome Skimming Data.

Bananas (Musa spp.) are some of the most important fruit crops in the world, contributing up to US$10 billion in export values annually. In this study, we use high-throughput sequencing to obtain genomic resources of high-copy DNA molecules in bananas. We sampled 13 wild species and eight cultivars that represent the three genera (Ensete, Musa, and Musella) of the banana family (Musaceae). Their plastomic, 45S rDNA, and mitochondrial scaffolds were recovered from genome skimming data. Two major clades (Clades I & II) within Musa are strongly supported by the three genomic compartment data. We document, for the first time, that the plastomes of Musaceae have expanded inverted repeats (IR) after they diverged from their two close relatives, Heliconiaceae (the lobster-claws) and Strelitziaceae (the traveler's bananas). The presence/absence of rps19 within IR regions reinforces the two intra-generic clades within Musa. Our comparisons of the bananas' plastomic and mitochondrial DNA sequence trees aid in identifying hybrid bananas' parentage. As the mitochondrial genes of Musa have elevated substitution rates, paternal inheritance likely plays an influential role on the Musa mitogenome evolution. We propose genome skimming as a useful method for reliable genealogy tracing and phylogenetics in bananas.

P–538 Potential involvement of testicular extracellular vesicles in the paternal epigenetic inheritance of undesirable metabolic traits

Abstract Study question Does high-fat diet alter the cargoes of testicular extracellular vesicles (tEVs) and thus modulate the sperm epigenome? Summary answer The properties and small RNA cargoes of tEVs and the sperm epigenome were significantly altered in mice fed with a high-fat diet. What is known already High-fat diet is known to alter spermatogenesis and sperm quality. Recent studies showed that the undesirable metabolic traits can be inherited to the next generation via paternal epigenetic inheritance. Hitherto, it has been shown that the extracellular vesicle, an important intercellular communication pathway, secreted by the epididymis conveys small RNA cargoes to sperms and mediate paternal epigenetic inheritance of metabolic traits. Surprisingly, although the sperm are first being produced in the testes, the potential contributions of testicular EVs (tEVs) in the sperm epigenome remain unexplored. Study design, size, duration It is a proof-of-concept study using mice as an experimental model. Thirty mice were raised for nine months, high-fat diet (HFD) and chow diet (SD) were treated on each half of the subject group starting from the sixth week until they were euthanized. Participants/materials, setting, methods: The study is conducted under laboratory settings. Sperm and tEVs were obtained from mice fed with HFD or SD. The uptake of tEVs by sperm was monitored by flow cytometry analysis using fluorescence-labelled tEVs. Physical properties of testicular EVs were examined by the transmission electron microscope. The small RNA cargoes were investigated by small RNA sequencing. The sperm epigenome was examined by real-time-qPCR. Main results and the role of chance Our results showed that sperm efficiently took up the tEVs in a dose-dependent manner, without compromising the sperm motility. Size of tEVs in HFD-fed mice (320.5 ± 99.83 nm) was significantly greater than that of SD-fed mice(251.9 ± 81.01 nm). RNA sequencing revealed a decrease in the percentage of miRNA in HFD tEVs. Eight miRNAs were differentially expressed in HFD tEVs. Among them, real-time PCR results confirmed that miR–34b and c levels were significantly up-regulated in HFD tEVs, with a log2[Fold-change] of 0.46613 and 0.42935 respectively. Unexpectedly, the levels of both miR–34b and c were similar in HFD and SD epididymis, and were both down-regulated by about 2-fold in matured sperm of HFD-fed mice. To investigate the cause of discrepancy, we carried out flow cytometry analysis to measure the absorption efficiency of tEVs, which revealed a notable decrease in absorption efficiency of HFD tEVs (70.235 ± 4.864%) by sperms compared to that of SD tEVs (79.350 ± 4.012%). Limitations, reasons for caution Cauda sperm was used in the profiling of sperm epigenome where the contributions from the epididymosomes have not been compared. The study was conducted using mice models such that discrepancy may occur when applying to humans. Wider implications of the findings: We revealed the alteration of tEVs in HFD-fed mice which may underlie the perturbation of spermatogenesis in HFD condition. We demonstrated the efficient uptake of tEVs by sperm which may be developed as a tool for the engineering of the sperm epigenome. Trial registration number Not applicable

P–093 The use of donor sperm improves post-ICSI live birth rates in advanced maternal age women

Abstract Study question Can the use of donor sperm improve post-ICSI live birth rate in advanced maternal age (AMA) patients? Summary answer The use of donor sperm increases post-ICSI live birth rate while substantially reducing abortion occurrence in AMA patients. What is known already Oocyte DNA repair capacity decreases with maternal age, when sperm DNA integrity is particularly important to avoid the transfer of gene truncations and de novo mutations to the zygote. Optimal DNA repair activity in the zygote requires paternal inheritance of 8-oxoguanine DNA glycosylase (OGG1), a rate-limiting enzyme in the base excision repair pathway. However, the involvement of paternal aging and sperm quality in the severe drop in fertility observed in AMA patients has not been addressed. While strategies to mitigate the impact of AMA on fertility have exclusively targeted oocyte quality, the sperm contribution in this scenario remains somehow neglected. Study design, size, duration Retrospective, multicentric, international study including 755 first ICSI cycles with patients’ own oocytes achieving a fresh ET between 2015 and 2019, 337 of which using normozoospermic partner semen and 418 using donor sperm. The association of sperm origin (partner vs. donor) with live birth was assessed by univariate/multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients. ICSI outcomes were compared between partner and donor sperm in non-AMA and AMA patients. Participants/materials, setting, methods The study was conducted in 3 fertility clinics including 755 Caucasian patients aged 24 to 42 years. Univariate/multivariate analyses were performed to test the association of sperm origin with live birth; infertility factor, maternal age, oocyte yield and number of embryos transferred were included in the model as confounding variables. In addition, ICSI outcomes were compared between donor and partner sperm groups with the Chi-square (percentages) or with the Wilcoxon sum rank (continuous variables) tests. Main results and the role of chance The multivariate analysis revealed that the use of donor sperm was positively and independently associated with live birth occurrence in AMA [1.82 OR (1.08–3.07) 95% IC; p = 0.024], but not in non-AMA patients [1.53 (0.94–2.51); p = 0.090]. Maternal age [0.75 (0.64–0.87); p < 0.001], number of MII oocytes recovered [1.14 (1.05–1.23); p = 0.001] and number of embryos transferred [1.90 (1.27–2.86); p = 0.002] were also independently associated with live birth in AMA patients. Live birth and delivery rates were 70–75% higher, while miscarriage rate was less than half in donor sperm compared to partner sperm AMA cycles (LBR: 25.4% vs. 14.5%, p = 0.003; DR: 22.5% vs. 13.5%, p = 0.008; MR: 18.0% vs. 39.5%; p = 0.009). Implantation (17.4% vs. 13.5%; p = 0.075) and clinical pregnancy rates (27.5% vs. 22.3%; p = 0.121) did not significantly differ between sperm donation and partner sperm AMA cycles. Male age was substantially lower (23.6 ± 5.2 vs. 41.4 ± 5.0; p < 0.0001) and oocyte yield was higher (5.1 ± 3.1 vs. 4.3 ± 2.6; p < 0.0001) in sperm donation compared to partner sperm AMA cycles, while maternal age did not vary (39.8 ± 1.6 vs. 39.6 ± 1.7; p = 0.348). Limitations, reasons for caution This study is limited by its retrospective nature and by differences in patients’ profiles between sperm donation and homologous cycles, although this variation has been controlled for in the statistical analysis. Wider implications of the findings: The findings suggest that donor sperm can improve live birth rates by drastically reducing miscarriage occurrence in AMA patients. Therefore, the present results may influence AMA treatment decisions and, above all, contribute for AMA patients to achieve a healthy birth. Trial registration number Not applicable

Parent–offspring variation transmission in full-sib families revealed predominantly paternal inheritance of chloroplast DNA in Pinus massoniana (Pinaceae)

Parent–offspring variation transmission in full-sib families revealed predominantly paternal inheritance of chloroplast DNA in Pinus massoniana (Pinaceae)

Phylogeographic review of Y chromosome haplogroups in Europe.

The Y chromosome has been widely explored for the study of human migrations. Due to its paternal inheritance, the Y chromosome polymorphisms are helpful tools for understanding the geographical distribution of populations all over the world and for inferring their origin, which is really useful in forensics. The remarkable historical context of Europe, with numerous migrations and invasions, has turned this continent into a melting pot. For this reason, it is interesting to study the Y chromosome variability and how it has contributed to improving our knowledge of the distribution and development of European male genetic pool as it is today. The analysis of Y lineages in Europe shows the predominance of four haplogroups, R1b-M269, I1-M253, I2-M438 and R1a-M420. However, other haplogroups have been identified which, although less frequent, provide significant evidence about the paternal origin of the populations. In addition, the study of the Y chromosome in Europe is a valuable tool for revealing the genetic trace of the different European colonizations, mainly in several American countries, where the European ancestry is mostly detected by the presence of the R1b-M269 haplogroup. Therefore, the objective of this review is to compile the studies of the Y chromosome haplogroups in current European populations, in order to provide an outline of these haplogroups which facilitate their use in forensic studies.

Nurse cell--derived small RNAs define paternal epigenetic inheritance in Arabidopsis.

The plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and regulates meiosis. Here, we reveal the molecular mechanism underlying this reprogramming. We demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by 24-nucleotide small interfering RNAs (siRNAs) transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) through activity of CLSY3, a chromatin remodeler absent in other anther cells. Tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Tapetum-derived siRNAs also silence germline transposons, safeguarding genome integrity. Our results reveal that tapetal siRNAs are sufficient to reconstitute germline methylation patterns and drive functional methylation reprogramming throughout the male germline.

Spatiotemporal Small Non-coding RNAs Expressed in the Germline as an Early Biomarker of Testicular Toxicity and Transgenerational Effects Caused by Prenatal Exposure to Nanosized Particles.

In recent years, an apparent decline in human sperm quality has been observed worldwide. One in every 5.5 couples suffers from infertility, with male reproductive problems contributing to nearly 40% of all infertility cases. Although the reasons for the increasing number of infertility cases are largely unknown, both genetic and environmental factors can be contributing factors. In particular, exposure to chemical substances during mammalian male germ cell development has been linked to an increased risk of infertility in later life owing to defective sperm production, reproductive tract obstruction, inflammation, and sexual disorders. Prenatal exposure to nanomaterials (NMs) is no exception. In animal experiments, maternal exposure to NMs has been reported to affect the reproductive health of male offspring. Male germ cells require multiple epigenetic reprogramming events during their lifespan to acquire reproductive capacity. Given that spermatozoa deliver the paternal genome to oocytes upon fertilization, we hypothesized that maternal exposure to NMs negatively affects male germ cells by altering epigenetic regulation, which may in turn affect embryo development. Small non-coding RNAs (including microRNAs, PIWI-interacting RNAs, tRNA-derived small RNAs, and rRNA-derived small RNAs), which are differentially expressed in mammalian male germ cells in a spatiotemporal manner, could play important regulatory roles in spermatogenesis and embryogenesis. Thus, the evaluation of RNAs responsible for sperm fertility is of great interest in reproductive toxicology and medicine. However, whether the effect of maternal exposure to NMs on spermatogenesis in the offspring (intergenerational effects) really triggers multigenerational effects remains unclear, and infertility biomarkers for evaluating paternal inheritance have not been identified to date. In this review, existing lines of evidence on the effects of prenatal exposure to NMs on male reproduction are summarized. A working hypothesis of the transgenerational effects of sperm-derived epigenomic changes in the F1 generation is presented, in that such maternal exposure could affect early embryonic development followed by deficits in neurodevelopment and male reproduction in the F2 generation.

Haplotype diversity and sequence heterogeneity of human telomeres.

Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.

Paternal inheritance predicts earlier cardiovascular event onset in patients with familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disease, with an autosomal codominant inheritance, predisposing to premature atherosclerotic cardiovascular disease (ASCVD). Paternal or maternal inheritance of the FH-causing mutation may affect the FH phenotype in offspring, but the effect of the genetic transmission on cardiovascular disease risk remains to be established.The aim of the present study is to compare the incidence of cardiovascular events between patients with maternal vs paternal inheritance of familial hypercholesterolemia. MethodsWe prospectively studied 725 genetically-confirmed FH patients (33,805 person-years), including 268 with maternal inheritance and 321 with paternal inheritance of the mutation. ASCVD was defined as angina, myocardial infarction, coronary angioplasty, coronary bypass surgery, claudication, peripheral angioplasty, peripheral arterial surgery, transient ischemic attack, stroke, carotid endarterectomy and CV death. Cox-proportional hazard models and Kaplan-Meier analysis were used to compare the two groups. ResultsBefore 50 years of age, paternal inheritance of FH was associated with a 1.5-fold increased risk for ASCVD, as compared to maternal inheritance (HR 1.59, 95% CI 1.11–2.28, p = 0.01). This association remained significant after adjusting for confounding factors (HR 1.49, 95% CI 1.00–2.23, p = 0.05). The age of first ASCVD event was also significantly lower in the paternal inheritance group (42 years) than in the maternal inheritance group (46 years), p = 0.02. ConclusionsThis study suggests that paternal inheritance of the FH-causing mutation was associated with an earlier cardiovascular event onset compared to maternal inheritance. The mechanisms behind these findings remain to be established.

THE INFLUENCE OF GENOTYPIC FACTORS ON LONGEVITY AND LIFETIME PRODUCTION OF DAIRY COWS

The influence of genotypic factors (breed, Holstein share heredity, line or related group, sire) on the longevity and lifetime production of dairy cows has been investigated. The study was carried out in a retrospective statistical experiment on the commercial dairy farm “Terezyne”, which located in Kyiv region. The formed matrix of observations in the sta format generally contained information about 5703 cows for 458 variables. Holstein cows were characterized by higher longevity (1489 ± 27.8 days) and higher lifetime milk production (21940 ± 500.9 kg), the lowest longevity and lifetime milk production had cows of Ukrainian Red-and-White dairy breed. Holstein cows compared to animals of Ukrainian Red-and-White dairy breed had in average more lactations (+0.57 ± 0.187) and higher number of total calves (+0.59 ± 0.244). They had an advantage in lifespan by 218 ± 80.1 days, productive lifespan – by 326 ± 82.0 days, total lactation length – by 282 ± 62.2 days. During the lifetime, they produced 4119 ± 1398.4 kg more milk and 549.3 ± 99.62 kg more milk fat and milk protein. Lifetime daily milk yield of Holstein cows was on average 2.6 ± 0.37 kg higher, lifetime daily milk fat and milk protein – 208 ± 26.7 g more compared to animals of the Ukrainian Red-and-White dairy breed. Cows of Ukrainian Black-and-White dairy breed in most traits were intermediate between Holstein and Ukrainian Red-and-White dairy breed. While increasing Holstein share heredity the longevity and lifetime production of cows tended for curvilinear growing. Lifetime of Holstein cows (100%) in the herd was 0.16 ± 0.405 lactations and 325 ± 170.7 days (P < 0.1) longer compared to animals with Holstein share heredity less than 75%. Their lifetime milk production was 8969 ± 2351.6 kg (P < 0.001) higher, lifetime milk fat and milk protein production by 709.9 ± 164.73 kg (P < 0.001) higher, lifetime daily yield by 3.0 ± 0.62 kg (P < 0.001) and 250 ± 43.5 g (P < 0.001), respectively, higher. The cows of Starbuck 352790, Valiant 1650414 and Elevation 1491007 lines and daughter of V. Astronomer 2160438 and H. R. Artist 6284191 sires showed the best longevity and lifetime production. The advantage of cows of the related group of Starbuck 352790 in comparison to animals of other lines in total number of lactations was 0.28–1.29, number of total calves – 0.16–1.20, lifespan – 90–508 days, productive lifespan – 116–603 days, total lactation length – 98–500 days, lifetime milk production – 1402–12161 kg, lifetime milk fat and milk protein production – 115–892 kg. Daughters of bull V. Astronomer 2160438 characterized by 0.96–2.72 more total number of lactations than daughters of other bulls; they had 0.80–2.33 higher average number of total calves. In terms of lifespan, productive lifespan and total lactation length, daughters of this bull were predominated the daughters of other bulls by 392–1037, 297–1143 and 278–971 days, respectively. One-way analysis of variance showed that the greatest influence on longevity and lifetime production of dairy cows had a paternal inheritance, the lowest – breed, it means there is a tendency of increasing the influence of genotypic factors on the researched traits while reducing the level of selection group in the system hierarchy. The strength of breed influence (higher level of intraspecific selection system hierarchy) on the traits of longevity and lifetime production of cows ranged from 1.1 to 12.5%, Holstein share heredity – 3.9 to 19.5%, line or related group – 4.0–19.8% and paternal inheritance – 25.0–47.6%. Greater degree of influence of paternal inheritance is explained both by the lowest (basic) level of intrabreed system hierarchy (the closest level of intragroup kinship) and (partially) by a much higher number of gradations of the organized factor.

Paternal leakage inheritance and a fitness cost are associated with the chloroplastic psbA gene controlled metribuzin tolerance in lentil (Lens culinaris)

Reciprocal F1, F2 and F3 populations of lentil (Lens culinaris Medik.) were developed by crossing between lines, with a chloroplastic psbA gene mutation conferring tolerance to the photosystem II inhibitor herbicide metribuzin, and sensitive parent PBA Flash, to understand the genetic control of the herbicide tolerance. Additionally, reciprocal BC1F2 populations were developed to identify any fitness penalty associated with the metribuzin tolerance. Phenotyping and genotyping results of the F1, F2, and F3 populations identified a predominantly maternal inheritance pattern, but with a level of paternal leakage. Paternal leakage occurred in approximately 20% of F1 phenotypes, when including lines showing heteroplasmy (the existence of maternal and paternal chloroplasts within an individual). Field experiments with BC1F2 and BC1F3 lines confirmed this biparental inheritance pattern. Grain yield was reduced by 20–40% in metribuzin tolerant backcrossed lines compared with sensitive lines. Net assimilation rate at the onset of anthesis and plant dry weight at mid anthesis and maturity were also reduced in the tolerant lines suggesting reduced photosynthetic efficiency associated with the metribuzin tolerance results in lower dry weight and grain yield in the tolerant lines. The mode of inheritance and associated yield penalty of the tolerance trait will complicate its introgression in lentil breeding programs. However, the high level of tolerance and unique weed control benefits of this trait suggest that this form of metribuzin tolerance in lentil, which is similar to triazine tolerant canola (Brassica napus L.), could be adopted.

Comparison of life history parameters of two different genetic clusters of Bemisia tabaci MED (Hemiptera: Aleyrodidae) through single and cross mating.

Bemisia tabaci Mediterranean (Gennadius) (Hemiptera: Aleyrodidae) is an economically important insect pest worldwide. Previously, we have reported that most B. tabaci Mediterranean (MED) populations occurring in greenhouse tomatoes in Korea have been displaced from well-differentiated two genetic clusters (C1 and C2) to one (C2) during one-year period. To elucidate factors responsible for this phenomenon, we compared life history parameters of these two different genetic clusters through single and cross mating experiments on two different host plants, cucumber and tobacco, at 26°C. Intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (Ro) were significantly higher in the dominating cluster (C2) (0.247, 1.280, and 192.402, respectively on cucumber; 0.226, 1.253, and 133.792, respectively on tobacco) than in the other cluster (C1) (0.149, 1.161, and 50.539, respectively on cucumber; 0.145, 1.156, and 53.332, respectively on tobacco). Overall performances of cross mating groups, C2fC1m (C2 female × C1 male) and C1fC2m (C1 female × C2 male), were in-between those of C2 and C1, with C2fC1m performing better than C1fC2m. Thus, maternal inheritance appeared to be significantly associated with their life history parameters, with partial involvement of paternal inheritance. Our results demonstrated that the rapid displacement of genetic clusters of B. tabaci MED populations was clearly associated with differences in their life history parameters.

An aggressive and expanded phenotype in a kindred with a c.57delG SDHD mutation

SummaryFamilial paraganglioma syndrome type 1 (PGL-1) is maternally imprinted, caused by SDHD mutations on the paternally inherited allele, and presents with paragangliomas and pheochromocytomas that are usually benign. We describe a kindred with a germline c.57delG SDHD mutation that demonstrates an aggressive and possibly expanded phenotype. Eight individuals across four generations were heterozygous for the c.57delG SDHD mutation. The three with known paternal inheritance were clinically affected. The aggressive phenotype was manifested by a neck paraganglioma with distant metastases, and to a lesser degree a neck paraganglioma infiltrating into local connective tissue and a pheochromocytoma presenting at age 8 y. A pulmonary capillary hemangioma may expand the SDHD phenotype. We conclude that the c.57delG SDHD mutation may confer a more aggressive and possibly expanded phenotype than other SDHD mutations.Learning points The c.57delG SDHD mutation may confer a more aggressive phenotype than other mutations associated with familial paraganglioma syndrome type 1. A capillary hemangioma, a component of other pseudohypoxia states, was observed in the lung of a single member of the c.57delG SDHD kindred. This report supports the hypothesis of others that mutations found near the beginning of the SDHD open reading frame are more likely to demonstrate an aggressive phenotype.

Clade-Specific Plastid Inheritance Patterns Including Frequent Biparental Inheritance in Passiflora Interspecific Crosses.

Plastid inheritance in angiosperms is presumed to be largely maternal, with the potential to inherit plastids biparentally estimated for about 20% of species. In Passiflora, maternal, paternal and biparental inheritance has been reported; however, these studies were limited in the number of crosses and progeny examined. To improve the understanding of plastid transmission in Passiflora, the progeny of 45 interspecific crosses were analyzed in the three subgenera: Passiflora, Decaloba and Astrophea. Plastid types were assessed following restriction digestion of PCR amplified plastid DNA in hybrid embryos, cotyledons and leaves at different developmental stages. Clade-specific patterns of inheritance were detected such that hybrid progeny from subgenera Passiflora and Astrophea predominantly inherited paternal plastids with occasional incidences of maternal inheritance, whereas subgenus Decaloba showed predominantly maternal and biparental inheritance. Biparental plastid inheritance was also detected in some hybrids from subgenus Passiflora. Heteroplasmy due to biparental inheritance was restricted to hybrid cotyledons and first leaves with a single parental plastid type detectable in mature plants. This indicates that in Passiflora, plastid retention at later stages of plant development may not reflect the plastid inheritance patterns in embryos. Passiflora exhibits diverse patterns of plastid inheritance, providing an excellent system to investigate underlying mechanisms in angiosperms.

Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome.

Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters—as well as that of kat6a—an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.

Pesticide-induced multigenerational effects on amphibian reproduction and metabolism

Underlying drivers of species extinctions need to be better understood for effective conservation of biodiversity. Nearly half of all amphibian species are at risk of extinction, and pollution may be a significant threat as seasonal high-level agrochemical use overlaps with critical windows of larval development. The potential of environmental chemicals to reduce the fitness of future generations may have profound ecological and evolutionary implications. This study characterized effects of male developmental exposure to environmentally relevant concentrations of the anti-androgenic pesticide linuron over two generations of offspring in Xenopus tropicalis frogs. The adult male offspring of pesticide-exposed fathers (F1) showed reduced body size, decreased fertility, and signs of endocrine system disruption. Impacts were further propagated to the grand-offspring (F2), providing evidence of transgenerational effects in amphibians. The adult F2 males demonstrated increased weight and fat body palmitoleic-to-palmitic acid ratio, and decreased plasma glucose levels. The study provides important cross-species evidence of paternal epigenetic inheritance and pollutant-induced transgenerational toxicity, supporting a causal and complex role of environmental contamination in the ongoing species extinctions, particularly of amphibians.

Forensic Application of Next Generation Sequencing Technology in the Typing of Y Chromosome Genetic Markers.

The paternal inheritance characteristics of Y chromosome have been widely used in the forensic genetics field to detect the genetic markers in the non-recombining block, and used in the studies such as, genetic relationship identification, mixed stain detection, pedigree screen and ethnicity determination. At present, capillary electrophoresis is still the most common detection technology. The commercial detection kits and data analysis and processing system based on this technology are very mature. However, the disadvantages of traditional detection technology have gradually appeared with the rapid growth of bio-information amount, which promotes the renewal of forensic DNA typing technology. In recent years, next generation sequencing （NGS） technology has developed rapidly. This technology has been applied to various fields including forensic genetics and has provided new techniques for the detection of Y chromosome genetic markers. This article describes the current situation and application prospects of the NGS technology in forensic Y chromosome genetic markers detection in order to provide new ideas for future judicial practice.

Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa.

Cadmium exposure is ubiquitous and has been linked to diseases including cancers and reproductive defects. Since cadmium is nonmutagenic, it is thought to exert its gene dysregulatory effects through epigenetic reprogramming. Several studies have implicated germline exposure to cadmium in developmental reprogramming. However, most of these studies have focused on maternal exposure, while the impact on sperm fertility and disease susceptibility has received less attention. In this study, we used reduced representation bisulfite sequencing to comprehensively investigate the impact of chronic cadmium exposure on mouse spermatozoa DNA methylation. Adult male C57BL/J6 mice were provided water with or without cadmium chloride for 9 weeks. Sperm, testes, liver, and kidney tissues were collected at the end of the treatment period. Cadmium exposure was confirmed through gene expression analysis of metallothionein-1 and 2, 2 well-known cadmium-induced genes. Analysis of sperm DNA methylation changes revealed 1788 differentially methylated sites present at regulatory regions in sperm of mice exposed to cadmium compared with vehicle (control) mice. Furthermore, most of these differential methylation changes positively correlated with changes in gene expression at both the transcription initiation stage as well as the splicing levels. Interestingly, the genes targeted by cadmium exposure are involved in several critical developmental processes. Our results present a comprehensive analysis of the sperm methylome in response to chronic cadmium exposure. These data, therefore, highlight a foundational framework to study gene expression patterns that may affect fertility in the exposed individual as well as their offspring, through paternal inheritance.

Generational Effects of Opioid Exposure.

Definition:The inheritance of substance abuse, including opioid abuse, may be influenced by genetic and non-genetic factors related to the environment, such as stress and socioeconomic status. These non-genetic influences on the heritability of a trait can be attributed to epigenetics. Epigenetic inheritance can result from modifications passed down from the mother, father, or both, resulting in either maternal, paternal, or parental epigenetic inheritance, respectively. These epigenetic modifications can be passed to the offspring to result in multigenerational, intergenerational, or transgenerational inheritance. Human and animal models of opioid exposure have shown generational effects that result in molecular, developmental, and behavioral alterations in future generations.

Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.