Maternal Transmission Research Articles

A Light in the Dark: Uncovering Wolbachia-Host Interactions Using Fluorescence Imaging.

The success of microbial endosymbionts, which reside naturally within a eukaryotic "host" organism, requires effective microbial interaction with, and manipulation of, the host cells. Fluorescence microscopy has played a key role in elucidating the molecular mechanisms of endosymbiosis. For 30years, fluorescence analyses have been a cornerstone in studies of endosymbiotic Wolbachia bacteria, focused on host colonization, maternal transmission, reproductive parasitism, horizontal gene transfer, viral suppression, and metabolic interactions in arthropods and nematodes. Fluorescence-based studies stand to continue informing Wolbachia-host interactions in increasingly detailed and innovative ways.

LIKE FATHER, LIKE DAUGHTER . . . OR LIKE MOTHER, LIKE DAUGHTER? Parental Models of Women Students at France’s Fourth Largest Engineering College (UTBM) in 1985–2016

This article analyses the feminisation of the student population of the University of Technology of Belfort-Montbéliard (UTBM) from its foundation to 2016. It positions the case of UTBM in the French landscape of engineering schools, but also in the academic discussions of the causes of the over-selection of girls (paternal or maternal transmission, other explanatory model). Thanks to the large number of files used (N = 14,243), a comparison of French, Chinese, and Moroccan students of UTBM makes it possible to identify national models of choice and transmission between parents and their children. For French students, paternal model is more influential, nevertheless the maternal model seems to determine with greater influence the choice of girls, in spite of the small number of mothers who are engineers.

The effects of temperature on prevalence of facultative insect heritable symbionts across spatial and seasonal scales.

Facultative inheritable endosymbionts are common and diverse in insects and are often found at intermediate frequencies in insect host populations. The literature assessing the relationship between environment and facultative endosymbiont frequency in natural host populations points to temperature as a major component shaping the interaction. However, a synthesis describing its patterns and mechanistic basis is lacking. This mini-review aims to bridge this gap by, following an evolutionary model, hypothesizing that temperature increases endosymbiont frequencies by modulating key phenotypes mediating the interaction. Field studies mainly present positive correlations between temperature and endosymbiont frequency at spatial and seasonal scales; and unexpectedly, temperature is predominantly negatively correlated with the key phenotypes. Higher temperatures generally reduce the efficiency of maternal transmission, reproductive parasitism, endosymbiont influence on host fitness and the ability to protect against natural enemies. From the endosymbiont perspective alone, higher temperatures reduce titer and both high and low temperatures modulate their ability to promote host physiological acclimation and behavior. It is necessary to promote research programs that integrate field and laboratory approaches to pinpoint which processes are responsible for the temperature correlated patterns of endosymbiont prevalence in natural populations.

Evaluation of COVID-19 Vertical Maternal Transmission with Respect to Foetal Visceral Maturation

Evaluation of COVID-19 Vertical Maternal Transmission with Respect to Foetal Visceral Maturation

Transmission mode predicts coinfection patterns of insect-specific viruses in field populations of the Queensland fruit fly.

Insect-specific viruses (ISVs) can affect insect health and fitness, but can also interact with other insect-associated microorganisms. Despite this, ISVs are often studied in isolation from each other, in laboratory populations. Consequently, their diversity, prevalence and associations with other viruses in field populations are less known, yet these parameters are important to understanding virus epidemiology. To help address this knowledge gap, we assessed the diversity, prevalence and coinfections of three ISVs (horizontally transmitted cripavirus, biparentally transmitted sigmavirus and maternally transmitted iflavirus) in 29 field populations of Queensland fruit fly, Australia's most significant horticultural pest, in the context of their different transmission modes. We detected new virus variant diversity. In contrast to the very high virus prevalence in laboratory populations, 46.8% of 293 field flies carried one virus and 4.8% had two viruses. Cripavirus and sigmavirus occurred in all regions, while iflavirus was restricted to subtropical and tropical regions. Cripavirus was most prevalent (37.5%), followed by sigmavirus (13.7%) and iflavirus (4.4%). Cripavirus coinfected some flies with either one of the two vertically transmitted viruses. However, sigmavirus did not coinfect individuals with iflavirus. Three different modelling approaches detected negative association patterns between sigmavirus and iflavirus, consistent with the absence of such coinfections in laboratory populations. This may be linked with their maternal transmission and the ineffective paternal transmission of sigmavirus. Furthermore, we found that, unlike sigmavirus and iflavirus, cripavirus load was higher in laboratory than field flies. Laboratory and mass-rearing conditions may increase ISV prevalence and load due to increased transmission opportunities. We conclude that a combination of field and laboratory studies is needed to uncover ISV interactions and further our understanding of ISV epidemiology.

Maternally inherited siRNAs initiate piRNA cluster formation

PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.

Maternal transmission of bacterial microbiota during embryonic development in a viviparous lizard.

The maternal transmission of microbiota during embryonic development of vertebrates is still poorly understood. Here, we used high-throughput sequencing of the 16S rRNA bacterial genes to determine the bacterial communities in the gastrointestinal tract and amniotic environment, i.e., the amniotic fluid, amniotic membrane and extraembryonic yolk, of embryos at the last stage of development of the viviparous lizard Sceloporus grammicus Wiegmann, 1828. We compared these communities to those found in the maternal intestine, mouth, cloaca, and the aseptic ventral skin as a control of the aseptic technique. Our results showed that bacterial 16S rRNA genes were present in the embryos of S. grammicus. Their diversity was lower and more similar in composition between individuals than those found in the maternal tissues. This suggests that a strong control exists on the transmission of bacteria from the mother to the embryos. We found 78% of the embryonic amplicon sequence variants (ASVs) in the maternal bacterial microbiota, suggesting that the transmission of bacteria from the mother to the embryos is a continuous process and some bacteria may have been transferred during early embryonic stages. The embryonic bacteria were found to overlap mostly with those found in the mouth and aseptic ventral skin of the mother, although it is difficult to conclude that the shared ASVs originated from these maternal tissues. Our study provides evidence of microbiota vertical transfer during embryonic development in the animal kingdom. It also highlights that this maternal transmission could be included in the maternal effects that impact the offspring.IMPORTANCEWe investigated the presence and diversity of bacteria in the embryos of the viviparous lizard Sceloporus grammicus and their amniotic environment. We compared this diversity to that found in the maternal intestine, mouth, and cloaca. We detected bacterial DNA in the embryos, albeit with a lower bacterial species diversity than found in maternal tissues. Most of the bacterial species detected in the embryos were also found in the mother, although not all of them. Interestingly, we detected a high similarity in the composition of bacterial species among embryos from different mothers. These findings suggest that there may be a mechanism controlling the transmission of bacteria from the mother to the embryo. Our results highlight the possibility that the interaction between maternal bacteria and the embryo may affect the development of the lizards.

SAT084 Maternally Inherited Diabetes With Deafness: A Rare And Challenging Diagnosis Of Diabetes

Abstract Disclosure: K. Cuan: None. I.R. Bass: None. Introduction: Maternally inherited diabetes with deafness (MIDD) is a rare mitochondrial disease with variable phenotypic expression characterized by a defect in insulin secretion and sensorineural hearing loss. Other potential features of MIDD include proximal myopathy, macular retinal dystrophy, and renal focal segmental glomerulosclerosis. Mitochondrial diseases are difficult to recognize given their heterogeneous presentation, however accurate diagnosis of MIDD is important as there are implications for management. DESCRIPTION: A 38-year-old adopted woman with previously diagnosed type 1 diabetes (T1DM), congenital deafness, and chronic kidney disease presented to our endocrinology clinic with concerns for difficulty controlling her blood glucose levels. She was diagnosed with T1DM at age 21 based on age and normal body habitus and was started on insulin. Due to insurance issues, she discontinued insulin use for several years and her diabetes was poorly controlled during that time, however, she never experienced diabetic ketoacidosis (DKA). Upon resuming insulin, she experienced multiple unpredictable episodes of hypoglycemia and subsequently self-discontinued insulin and presented 8 months later for further care. Past history was notable for muscle weakness with walking upstairs and vision loss in her left eye, which led to a diagnosis of retinopathy in her early twenties. Her family history was unavailable as she was adopted. Her physical exam was significant for a normal body mass index of 24. Labs showed a hemoglobin A1C of 10.8% and detectable c-peptide, 2.7 ng/mL (1.1-4.4 ng/mL) with a glucose of 192mg/dL. Glutamic acid decarboxylase, zinc transporter 8, IA-2 and islet-cell antibodies were all negative. Her creatinine was 1.23 ng/dL with a severely increased microalbumin to creatinine ratio (638, 0-29 mg/g). In view of her congenital deafness, non-diabetic retinopathy, absence of DKA while off insulin, negative antibody testing, and chronic kidney disease, mitochondrial diabetes was considered. She was referred to a geneticist for mitochondrial genome sequencing, of which the results are pending. Dietary modification and oral agents were recommended for her diabetes management, rather than insulin therapy. DISCUSSION: MIDD can be challenging to diagnose and patients may be incorrectly labeled as having type 1 diabetes. The presence of maternal transmission can aid in the diagnosis of MIDD, however, our patient was adopted and this information is unavailable. Additionally, retinal and renal features of MIDD can be misconstrued as microvascular complications of diabetes. In patients with deafness and poorly controlled diabetes with negative antibody testing, MIDD should be considered as an alternative diagnosis. MIDD can be managed with dietary modification, oral agents, and insulin if appropriate. Presentation: Saturday, June 17, 2023

Oral Microbiota: A New Insight into Cancer Progression, Diagnosis and Treatment.

The polymorphic microbiome has been defined as one of the "Hallmarks of Cancer". Extensive studies have now uncovered the role of oral microbiota in cancer development and progression. Bacteria, fungi, archaea, and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis. This complex interaction is influenced by many factors, such as maternal transmission, personal factors and environmental factors. Dysbiosis of oral microbiota can disturbed this host-microbiota interaction, leading to systemic diseases. Numerous studies have shown the potential associations between oral microbiota and a variety of cancers. However, the underlying mechanisms and therapeutic insights are still poorly understood. In this review, we mainly focus on the following aspects: (1) the factors affect oral microbiota composition and function; (2) the interaction between microenvironment and oral microbiota; (3) the role of multi-kingdom oral microbiota in human health; (4) the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer. Finally, we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.

Seroprevalence of Hepatitis B, Hepatitis C, and HIV Infections Among Pregnant Women and Newborns in Mogadishu, Somalia: A Four-Year Retrospective Study

In Somalia, the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections have different distributions according to gender, age, geographical regions of the country with different conditions, and subgroups of the population which have different characteristics or a specific disease. After the increasing number of general prevalence studies across the country in recent years, the need to examine the prevalence of relevant viral infections in subgroups of the society, which are especially important for public health, has arisen. In this study, it was aimed to investigate the frequency and epidemiological characteristics of HBV, HCV, and HIV infections in pregnant women and children under one year of age who admitted to our hospital. In our study, between 2015-November and 2019-November, 4,274 pregnant women (Group 1; mean age of 26.3±5.697 and an age range of 15-49) who were followed up or delivered in our hospital, 1,534 non-pregnant female patients with various diseases (Group 2; mean age 34.5±12.589 years, age range 15-95), and 1,059 infants under one age were retrospectively investigated. Newborn (<1 month) in the third group were also examined as a subgroup. The seroprevalence of anti-HBs, HBsAg, anti-HCV, and anti-HIV, which are viral infection markers, in pregnant women were found as 17.2% (n=644), 2.8% (n=116), 0.17% (n=7), and 0.14% (n=6), respectively. In non-pregnant women, the seroprevalence of anti-HBs, HBsAg, and anti-HCV were found as 27% (n=324), 6.4% (n=95), and 1% (n=14), respectively, and these rates were significantly higher than in pregnant women (Group 1) (p<0.001). The anti-HIV seropositivity rate in non-pregnant women (Group 2) was 0.07% (n=1), and this value was lower than the incidence in pregnant women (p=0.6881). In infants (Group 3), the seroprevalence of anti-HBs, HBsAg, anti-HCV, and anti-HIV was found as 35.6% (n=320), 0.8% (n=9), 1.4% (n=14), and 0.4% (n=4), respectively. High anti-HBs seropositivity was associated with the vaccination campaign carried out across the country and in our hospital. While HBsAg seroprevalence in infants was very low compared to hospital-wide data (0.8% vs. 8.1%), anti-HCV seroprevalence (1.4%) was similar to hospital-wide data (1.41%). Anti-HIV seroprevalence in infants (0.4%) was higher than both hospital-wide data (0.32%) and prevalence data for under 15s (0.15%). The high rate of anti-HBs due to vaccination was also notable in the newborns subgroup, however three (1.09%) newborn babies were HBsAg positive, indicating vertical maternal transmission. Similarly, two out of four HIV-infected infants (50%) were diagnosed in the neonatal period, indicating mother-to-child transmission. Our study data show that in Mogadishu, a region where access to treatment is easier than in the rest of the country, the impact of HBV infection tends to decrease, however HBV and HCV infections and HIV infections, although at low prevalence, continue to be transmitted from mothers to their babies. We think that the results of this study are valuable, especially in terms of revealing the changing trends in the epidemiology of infections in the region.

Microsporidia MB in the primary malaria vector Anopheles gambiae sensu stricto is avirulent and undergoes maternal and horizontal transmission

BackgroundThe demonstration that the recently discovered Anopheles symbiont Microsporidia MB blocks malaria transmission in Anophelesarabiensis and undergoes vertical and horizontal transmission suggests that it is a promising candidate for the development of a symbiont-based malaria transmission-blocking strategy. The infection prevalence and characteristics of Microsporidia MB in Anopheles gambiae sensu stricto (s.s.), another primary vector species of malaria in Kenya, were investigated.MethodsField-collected females were confirmed to be Microsporidia MB-positive after oviposition. Egg counts of Microsporidia MB-infected and non-infected individuals were used to infer the effects of Microsporidia MB on fecundity. The time to pupation, adult sex ratio and survival were used to determine if Microsporidia MB infection has similar characteristics in the host mosquitoes An. gambiae and An. arabiensis. The intensity of Microsporidia MB infection in tissues of the midgut and gonads, and in carcasses, was determined by quantitative polymerase chain reaction. To investigate horizontal transmission, virgin males and females that were either Microsporidia MB-infected or non-infected were placed in standard cages for 48 h and allowed to mate; transmission was confirmed by quantitative polymerase chain reaction targeting Microsporidia MB genes.ResultsMicrosporidia MB was found to naturally occur at a low prevalence in An. gambiae s.s. collected in western Kenya. Microsporidia MB shortened the development time from larva to pupa, but other fitness parameters such as fecundity, sex ratio, and adult survival did not differ between Microsporidia MB-infected and non-infected hosts. Microsporidia MB intensities were high in the male gonadal tissues. Transmission experiments indicated that Microsporidia MB undergoes both maternal and horizontal transmission in An. gambiae s.s.ConclusionsThe findings that Microsporidia MB naturally infects, undergoes maternal and horizontal transmission, and is avirulent in An. gambiae s.s. indicate that many of the characteristics of its infection in An. arabiensis hold true for the former. The results of the present study indicate that Microsporidia MB could be developed as a tool for the transmission-blocking of malaria across different Anopheles species.Graphical

Evidence of isotopic maternal transmission influence on bluefin tuna (Thunnus thynnus) larval growth

Pre-flexion stages of Atlantic bluefin tuna (Thunnus thynnus) larvae were collected in 2014 during the peak of spawning in the two main spawning areas: Gulf of Mexico (GOM) and Mediterranean Sea (MED). We examined daily growth, otolith biometry, and stable isotopes and found that the GOM grew at a faster rate, had larger otoliths, wider daily increments, and significantly lower values of δ15N when compared to the MED. In addition, an intra-population comparative analysis between slow- and fast-growing individuals (deficient vs. optimal growth groups, respectively) showed that optimal growth groups had significantly lower δ15N within each spawning area, implying a direct relationship between growth potential, development, and maternal transmission of isotopic signatures. A third pre-flexion larval group that was aquaculture-reared also exhibited the same pattern to the wild larval groups. In addition, for the first time, we estimated the maternal trophic niches using models developed with field-captured pre-flexion larvae. The estimated maternal trophic niches for the GOM were narrower than the MED, implying differences in the maternal trophodynamics from each nursery area. Overall, the inter-population (GOM vs. MED) and intra-population growth groups (deficient vs. optimal) grew faster and had narrower maternal niches. This study shows the advantages that larval SIA research can aid in the understanding of the trophodynamics of their breeders by examining the trophic relationship of a spawning stock jointly with the development of growth potential in offspring within the same breeding season.

Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study.

Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

Cost-effectiveness of tenofovir prophylaxis during pregnancy for the elimination of mother-to-child transmission of the hepatitis B virus: real-world analysis from Thailand

ObjectiveDespite implementing hepatitis B immunoglobulin (HBIG) and vaccination, data suggest it would not be sufficient to reach the elimination targets. Tenofovir disoproxil fumarate (TDF) has been added to the Thai...

Proposal of Model for Evaluation of Viral Kinetics of African/Asian/Brazilian-Zika virus Strains (Step Growth Curve) in Trophoblastic Cell Lines.

The Zika virus (ZIKV) epidemic brought new discoveries regarding arboviruses, especially flaviviruses, as ZIKV was described as sexually and vertically transmitted. The latter shows severe consequences for the embryo/fetus, such as congenital microcephaly and deficiency of the neural system, currently known as Congenital ZIKV Syndrome (CZS). To better understand ZIKV dynamics in trophoblastic cells present in the first trimester of pregnancy (BeWo, HTR-8, and control cell HuH-7), an experiment of viral kinetics was performed for African MR766 low passage and Asian-Brazilian IEC ZIKV lineages. The results were described independently and demonstrated that the three placental cells lines are permissive and susceptible to ZIKV. We noticed cytopathic effects that are typical in in vitro viral infection in BeWo and HTR-8. Regarding kinetics, MR766lp showed peaks of viral loads in 24 and 48 hpi for all cell types tested, as well as marked cells death after peak production. On the other hand, the HTR-8 lineage inoculated with ZIKV-IEC exhibited increased viral production in 144 hpi, with a peak between 24 and 96 hpi. Furthermore, IEC had peak variations of viral production for BeWo in 144 hpi. Considering such in vitro results, the hypothesis that maternal fetal transmission is probably a way of virus transmission between the mother and the embryo/fetus is maintained.

Temporal progression of anaerobic fungal communities in dairy calves from birth to maturity.

Establishment of microbial communities in neonatal calves is vital for their growth and overall health. While this process has received considerable attention for bacteria, our knowledge on temporal progression of anaerobic gut fungi (AGF) in calves is lacking. Here, we examined AGF communities in faecal samples from six dairy cattle collected at 24 different time points during the pre-weaning (days 1-48), weaning (days 48-60), and post-weaning (days 60-360) phases. Quantitative polymerase chain reaction indicated that AGF colonisation occurs within 24 h after birth, with loads slowly increasing during pre-weaning and weaning, then drastically increasing post-weaning. Culture-independent amplicon surveys identified higher alpha diversity during pre-weaning/weaning, compared to post-weaning. AGF community structure underwent a drastic shift post-weaning, from a community enriched in genera commonly encountered in hindgut fermenters to one enriched in genera commonly encountered in adult ruminants. Comparison of AGF community between calves day 1 post-birth and their mothers suggest a major role for maternal transmission, with additional input from cohabitating subjects. This distinct pattern of AGF progression could best be understood in-light of their narrower niche preferences, metabolic specialisation, and physiological optima compared to bacteria, hence eliciting a unique response to changes in feeding pattern and associated structural GIT development during maturation.

Maternal transmission gives way to social transmission during gut microbiota assembly in wild mice

BackgroundThe mammalian gut microbiota influences a wide array of phenotypes which are relevant to fitness, yet knowledge about the transmission routes by which gut microbes colonise hosts in natural populations remains limited. Here, we use an intensively studied wild population of wood mice (Apodemus sylvaticus) to examine how vertical (maternal) and horizontal (social) transmission routes influence gut microbiota composition throughout life.ResultsWe identify independent signals of maternal transmission (sharing of taxa between a mother and her offspring) and social transmission (sharing of taxa predicted by the social network), whose relative magnitudes shift as hosts age. In early life, gut microbiota composition is predicted by both maternal and social relationships, but by adulthood the impact of maternal transmission becomes undetectable, leaving only a signal of social transmission. By exploring which taxa drive the maternal transmission signal, we identify a candidate maternally-transmitted bacterial family in wood mice, the Muribaculaceae.ConclusionOverall, our findings point to an ontogenetically shifting transmission landscape in wild mice, with a mother’s influence on microbiota composition waning as offspring age, while the relative impact of social contacts grows.

Spectrum of Cytomegalovirus (CMV) Infection from a Tertiary Care Neonatal ICU in Resource Limited Settings

Cytomegalovirus (CMV) infection is the most common viral infection in perinatal period, which can occur in neonates from mother, in utero (congenital) via placenta, during birth from birth canal or more commonly postnatally from maternal breast milk or blood product transmission. In premature infants in many instances it can lead to severe manifestations resulting in increased morbidities and mortality. In this case series we share our experience on the clinicodemographic profile for CMV infections in neonatal intensive care unit and subsequent challenges related to its early detection and timely treatment in resource limited settings.

Social deficits in mice prenatally exposed to valproic acid are intergenerationally inherited and rescued by social enrichment

Intergenerational transmission of the effects of environmental factors on brain function and behavior can occur through epigenetic mechanisms. Valproic acid (VPA) is an anticonvulsant drug that, when administered during pregnancy, causes various birth defects. The mechanisms of action are largely unclear: VPA can reduce neuronal excitability, but it also inhibits the histone deacetylases, affecting gene expression. Here we evaluated whether the effects of valproic acid prenatal exposure on autism spectrum disorder (ASD)-related behavioral phenotypes can be transmitted to the second generation (F2) through the paternal or the maternal lineage. Indeed, we found that F2 males of the VPA pedigree show reduced sociability, which can be rescued by exposing the animals to social enrichment. Moreover, as is the case for F1 males, F2 VPA males show increased c-Fos expression in the piriform cortex. However, F3 males show normal sociability, indicating that VPA’s effects on this behavior are not transgenerationally inherited. Female behavior is not affected by VPA exposure, and we found no evidence of maternal transmission of the consequences of this pharmacological treatment. Finally, all animals exposed to VPA and their descendants show reduced body weight, highlighting an intriguing effect of this compound on metabolism. We propose the VPA model of ASD as a valuable mouse model to study the role of epigenetic inheritance and its underlying mechanisms affecting behavior and neuronal function.

Maternal transmission of dysmenorrhea includes substantial genetic influence.

aDepartment of Pain Medicine, Sydney Children's Hospital, Bright Alliance Building, Randwick, Australia bSchool of Clinical Medicine, University of NSW, Kensington, Australia *E-mail address: [email protected] (G. D. Champion) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.