Development Of Offspring Research Articles

A “toxic window” study on the hippocampal development of mice offspring exposed to azithromycin at different doses, courses, and time during pregnancy

BackgroundAzithromycin, one of the new-generation macrolides, is an effective medicine for the treatment of mycoplasma infection during pregnancy. Epidemiological studies have reported adverse pregnancy outcomes with prenatal azithromycin exposure (PAzE). However, the effect of PAzE on fetal hippocampal development is unclear. This study aimed to explore the effects and potential mechanism of PAzE-induced fetal hippocampal development at different doses, courses, and time. MethodPregnant mice were administered azithromycin by gavage at different doses (50, 100 or 200 mg/kg.d), different courses (gestational day (GD)15–17 for three consecutive days, or GD17 once a day) and different time (GD10-12, GD15-17). ResultsCompared with the control group, morphological development damage of the fetal hippocampus was observed in the PAzE group, with a dysbalance in neuronal proliferation and apoptosis, decreased expression of the neuronal-specific marker Snap25, NeuN, PSD95 and Map2, increased expression of the glial-specific marker Iba1, GFAP, and S-100β, and decreased expression of P2ry12. The PAzE-induced hippocampal developmental deficiency varied based on different doses, courses, and time, and the developmental toxicity was most significant in the late pregnancy, high dose, multi-course group (AZHT). The significant reduction of SOX2 and Wnt, which were related to regulation of neural progenitor cells (NPCs) proliferation in PAzE fetus compared with the control group indicated that the SOX2/Wnt signaling may be involved in PAzE-induced hippocampal developmental toxicity. ConclusionIn this study, PAzE was associated with hippocampal developmental toxicity in a variety of nerve cells. Hippocampal developmental toxicity due to azithromycin was most significant in the late pregnancy, high-dose (equivalent to maximum clinical dose) and multi-course group (AZHT). The findings provide an experimental and theoretical foundation for guiding the sensible use of medications during pregnancy and effectively assessing the risk of fetal hippocampal developmental toxicity.

Placental inflammatory cytokines mRNA expression and preschool children’s cognitive performance: a birth cohort study in China

BackgroundThe immunologic milieu at the maternal–fetal interface has profound effects on propelling the development of the fetal brain. However, accessible epidemiological studies concerning the association between placental inflammatory cytokines and the intellectual development of offspring in humans are limited. Therefore, we explored the possible link between mRNA expression of inflammatory cytokines in placenta and preschoolers’ cognitive performance.MethodsStudy subjects were obtained from the Ma’anshan birth cohort (MABC). Placental samples were collected after delivery, and real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the mRNA expression levels of IL-8, IL-1β, IL-6, TNF-α, CRP, IFN-γ, IL-10, and IL-4. Children’s intellectual development was assessed at preschool age by using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Multiple linear regression and restricted cubic spline models were used for statistical analysis.ResultsA total of 1665 pairs of mother and child were included in the analysis. After adjusting for confounders and after correction for multiple comparisons, we observed that mRNA expression of IL-8 (β = − 0.53; 95% CI, − 0.92 to − 0.15), IL-6 (β = − 0.58; 95% CI, − 0.97 to − 0.19), TNF-α (β = − 0.37; 95% CI, − 0.71 to − 0.02), and IFN-γ (β = − 0.31; 95% CI, − 0.61 to − 0.03) in the placenta was negatively associated with preschoolers’ full scale intelligence quotient (FSIQ). Both higher IL-8 and IL-6 were associated with lower children’s low fluid reasoning index (FRI), and higher IFN-γ was associated with lower children’s working memory index (WMI). After further adjusting for confounders and children’s age at cognitive testing, the integrated index of six pro-inflammatory cytokines (index 2) was found to be significantly and negatively correlated with both the FSIQ and each sub-dimension (verbal comprehension index (VCI), visual spatial index (VSI), FRI, WMI, processing speed index (PSI)). Sex-stratified analyses showed that the association of IL-8, IFN-γ, and index 2 with children’s cognitive development was mainly concentrated in boys.ConclusionsEvidence of an association between low cognitive performance and high expression of placental inflammatory cytokines (IL-8, IL-6, TNF-α, and IFN-γ) was found, highlighting the potential importance of intrauterine placental immune status in dissecting offspring cognitive development.

Evaluation of physiological and immunological parameters in the offspring born from passively smoking rats treated with neuropeptides

The results of physiological and immunological studies of rat pups born from females who were exposed to passive smoking and exposure to tetrapeptide KK1 during pregnancy are presented. From the 1st to the 21st postnatal days, the somatic and sensorimotor development of offspring was studied using a set of tests developed at the P.K. Anokhin Institute of Normal Physiology. The level of cytokines IFN gamma and IL-6 produced by rat splenocytes was studied in culture fluid by the ELISA method. In baby rats born from passively smoking females, compared with animals born from non-smoking rats, a decrease in the weight of baby rats was found, as well as a delay in the timeliness of somatic and sensorimotor development. The introduction of the peptide KK 1 non-smoking females increases the index of timeliness of somatic and sensorimotor development.
 The results obtained show an induced variant of secondary immunodeficiency in baby rats born from passively smoking rats during pregnancy. Administration of the KK1 peptide to non-smoking rats did not change the immunological parameters of the baby rats. On the contrary, the production of peptide KK1 by pregnant rats who smoked was accompanied by changes in the number of cells in lymphoid organs and the production of cytokines by splenocytes in the born rats.

Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes†.

Entering pregnancy with a history of adversity, including adverse childhood experiences and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28-70 and were mated 2 weeks post-stress. Maternal preconception stress dams blunted the pregnancy-induced shift in the circulating extracellular vesicle proteome and reduced glucose tolerance at mid-gestation, suggesting a shift in pregnancy adaptation. To investigate MPS effects at the maternal:fetal interface, we probed the mid-gestation placental, uterine, and fetal brain tissue transcriptome. Male and female placentas differentially regulated expression of genes involved in growth and metabolic signaling in response to gestation in an MPS dam. We also report novel offspring sex- and MPS-specific responses in the uterine tissue apposing these placentas. In the fetal compartment, MPS female offspring reduced expression of neurodevelopmental genes. Using a ribosome-tagging transgenic approach we detected a dramatic increase in genes involved in chromatin regulation in a PVN-enriched neuronal population in females at PN21. While MPS had an additive effect on high-fat-diet (HFD)-induced weight gain in male offspring, both MPS and HFD were necessary to induce significant weight gain in female offspring. These data highlight the preconception period as a determinant of maternal health in pregnancy and provides novel insights into mechanisms by which maternal stress history impacts offspring developmental programming.

Associations of maternal prenatal psychological symptoms and saliva cortisol with neonatal meconium microbiota: A cross-sectional study

Alterations in the diversity and relative abundances of the gut microbiome have been associated with a broad spectrum of medical conditions. Maternal psychological symptoms during pregnancy may impact on offspring development by altering the maternal and the foetal gut microbiome. We aimed to investigate whether self-reported maternal anxiety, depressive symptoms, and distress as well as saliva cortisol levels in late pregnancy alter the bacterial composition of the infant's meconium. MethodsA total of N = 100 mother-infant pairs were included. Maternal psychological symptoms were measured using psychological questionnaires (EPDS, PSS-10, STAI) at 34–36 weeks gestation and salivary cortisol was measured at 34–36 and 38 weeks gestation. Infant meconium samples were collected in the first five days postpartum and analysed using 16S rRNA amplicon sequencing. ResultsCorrelations showed that lower alpha diversity of the meconium microbiome was significantly associated with increased maternal prenatal depressive symptoms in late gestation (τ = −0.15, p = .04). Increased saliva cortisol AUCg at T2 was significantly related to higher beta diversity of the meconium samples (Pr(>F) = 0.003*). Pseudomonas was the most abundant phylum and was associated with maternal saliva cortisol total decline. No other associations were found. ConclusionsMaternal prenatal depressive symptoms are associated with infant faecal microbiome alpha diversity, whereas maternal saliva cortisol AUCg is linked to increased beta diversity and total decline related to increased Psuedomonas. Future studies are warranted to understand how these microbiota community alterations are linked to child health outcomes.

Mothers in a cooperatively breeding bird increase investment per offspring at the pre-natal stage when they will have more help with post-natal care.

In many cooperative societies, including our own, helpers assist with the post-natal care of breeders' young and may thereby benefit the post-natal development of offspring. Here, we present evidence of a novel mechanism by which such post-natal helping could also have beneficial effects on pre-natal development: By lightening post-natal maternal workloads, helpers may allow mothers to increase their pre-natal investment per offspring. We present the findings of a decade-long study of cooperatively breeding white-browed sparrow-weaver, Plocepasser mahali, societies. Within each social group, reproduction is monopolized by a dominant breeding pair, and non-breeding helpers assist with nestling feeding. Using a within-mother reaction norm approach to formally identify maternal plasticity, we demonstrate that when mothers have more female helpers, they decrease their own post-natal investment per offspring (feed their nestlings at lower rates) but increase their pre-natal investment per offspring (lay larger eggs, which yield heavier hatchlings). That these plastic maternal responses are predicted by female helper number, and not male helper number, implicates the availability of post-natal helping per se as the likely driver (rather than correlated effects of group size), because female helpers feed nestlings at substantially higher rates than males. We term this novel maternal strategy "maternal front-loading" and hypothesize that the expected availability of post-natal help either allows or incentivizes helped mothers to focus maternal investment on the pre-natal phase, to which helpers cannot contribute directly. The potential for post-natal helping to promote pre-natal development further complicates attempts to identify and quantify the fitness consequences of helping.

Effects of different volumes of ovariectomy on fertility and offspring development of rats.

The purpose of this study was to explore the effect of removal of different volumes of ovarian tissue on fertility and offspring development of SD rats. SD rats were randomly divided into 6 groups according to different volumes of ovariectomy: Sham group (n=6), non-ovariectomized; 25%-OVX group (n=6), with half of the left ovary excised; 50%-OVX group (n=5), with the left ovary excised; 75%-OVX group (n=5), with the left ovary and half of the right ovary excised; 87.5%-OVX group (n=6), with the left ovary and three quarters of the right ovary excised; 100%-OVX group (n=6), with bilateral ovaries excised. These female rats (F0) were mated with healthy male rats one and four months after the surgery, and the offspring of F0 rats were named F11mon and F14mon, respectively. The number of days from mating to delivery and number of live cubs were recorded. At postnatal day 21 (P21), the body weight, length and anogenital distance (AGD) of the cubs were measured. There were no differences in the number of live cubs between 25%-OVX, 50%-OVX and sham groups. Rats in the 87.5%-OVX group did not give birth at 1 month and 4 months after the operation. When compared with the sham group, the body weight and length of F11mon at P21 were increased in 25%-OVX group and 50%-OVX group. However, after the second delivery, we controlled each mother's lactation to no more than eight pups. As a result, there were no differences in the body weight, length and AGD of F14mon compared with sham group. Removal of less than 50% of the ovaries did not affect the fertility of rats and offspring development of rats.

15 Effects of the Maternal Gut and Reproductive Microbiome on Postnatal Development in Ruminants

Abstract The microbial communities residing within the gastrointestinal and reproductive tracts are vital to cattle health; not only for their involvement in nutrient metabolism, but also for their ability to influence infectious and metabolic diseases as well as reproductive efficiency. Therefore, harnessing the ruminal and vagino-uterine microbiomes for improved cattle health and productivity have recently become an active area of research in an era where microbiome manipulation holds as much potential as genetic selection and management refinement for enhancing herd productivity. New developments highlight that the maternal gut and reproductive microbiome extend their impact to offspring development and health. These developments include the demonstrations of maternal gut microbiota involvement in developmental programming in murine models, and increased evidence supporting the existence of in utero microbial colonization and the role of maternal nutrition on fetal programming in cattle. Our recent work has focused on understanding the role of the maternal microbiota and feto-maternal microbial crosstalk in fetal programming and offspring microbiome development. Our lab has investigated the impacts of maternal dietary restriction, supplementation of one carbon metabolites or vitamins and minerals during gestation on maternal ruminal and vaginal microbiota; as well as pre- and postnatal microbial colonization in offspring calves. Our results indicate that maternal dietary alterations during pregnancy may influence ruminal and vaginal microbiota of dams, which may subsequently impact early life microbial colonization in calves being gestated. Our findings call for further research in the area of maternal gut and reproductive microbiome alterations and their impacts on fetal programming and offspring development in ruminants.

PSV-8 Maternal Live Yeast Supplementation Improved Gut Health in Suckling and Weaned Piglets

Abstract Recent studies have highlighted the importance of maternal nutritional intervention in modulating the gastrointestinal development and health of offspring. The objective of this study was to determine the effects of live yeast supplementation to sows during late gestation and lactation periods on the gut health of piglets pre-weaning and immediately post-weaning. Based on parity and expected farrowing dates, on d 77 of gestation, 40 sows were allotted to 2 dietary treatments: without (CON) or with (LY) live yeast supplementation at 0.05% of diet during gestation and 0.1% during lactation. On postnatal days (PND) 0, 10, 18, and post-weaning days (PWD) 7 and 14, one piglet from 10 sows per treatment was selected for intestinal tissue collection (n = 10). Results showed that maternal LY supplementation increased mRNA expression of interleukin (IL)-6 on PND 18 and IL-1β on PWD 14 in the ileal mucosa (P < 0.05), with a tendency for greater IL-10 on PND 18 (P = 0.08). Additionally, LY piglets had increased mRNA expression of superoxide dismutase 1 on PND 10, 18, and PWD 14 (P < 0.05) and tended to have a greater mRNA abundance of catalase on PND 14 in the ileal mucosa (P = 0.09). Compared with CON piglets, LY piglets had an increased protein abundance of E-cadherin on PND 0, PWD 7, and 14 in the jejunal mucosa (P < 0.05). The LY piglets also had a greater protein abundance of occludin and claudin-4 in the jejunal mucosa on PWD 14 (P < 0.05). However, no differences were found for jejunal histomorphological measurements between treatments (P > 0.05). In conclusion, maternal LY supplementation may have a long-term protective effect on gut health of offspring by regulating the expression of tight junction proteins, inflammatory response, and antioxidant capacity.

290 Ewe Undernutrition Alters Cotyledon Development and Function

Abstract Undernutrition is common for animals maintained in a range setting, particularly during periods of drought, and during gestation can be detrimental to offspring development. The placenta is a known mediator for maternal-fetal nutrient exchange, and developmental impacts to the placenta during times of nutritional stress contribute to poor offspring outcomes. The objective of this study was to determine the impacts of maternal nutrient restriction on the development and function of placental cotyledons. Targhee ewes were allocated into two dietary treatment groups for the entirety of gestation. The control group (CON; n = 10) was fed to meet 100% of NRC requirements and the nutrient restricted group (NR; n = 11) was fed to meet 60% of NRC requirements, to mimic the nutritional stress experienced by range ewes during drought. At the time of lambing total placental weight, total cotyledon number, and lamb birth weight were recorded. Cotyledons (n = 3 / placenta) were removed from multiple locations, weighed, and processed for RNA-sequencing. Total placental weight, total cotyledon number, and lamb birth weight were not affected by maternal diet restriction (P > 0.05). Average cotyledon weight was greater in the CON group compared with the NR group (P < 0.05). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathways (KEGG) analyses were performed to identify biological pathways involved in placental function and nutrient transfer. Cotyledons from NR singletons vs CON singletons expressed 470 differentially expressed genes (DEGs; P < 0.05; 187 up-regulated, 283 down-regulated). Gene ontology terms represented by DEGs include hormone activity (P = 0.0003) and antigen processing and presentation (P = 0.0004). KEGG pathways of interest include pyruvate metabolism, estrogen signaling, extracellular matrix receptor interaction, and antigen processing and presentation. There were also 426 DEGs (P < 0.05; 195 up-regulated, 231 down-regulated) in cotyledons of NR twins vs CON twins. Represented GO categories include heme binding (P = 0.003) and oxidoreductase activity (P = 0.03). These data show that prolonged nutrient restriction alters cotyledon development and gene expression indicating modifications in placental function. These changes in placental function likely mediate poor offspring developmental outcomes observed following gestational under nutrition.

Influence of Maternal BLV Infection on miRNA and tRF Expression in Calves.

Small non-coding RNAs, such as microRNAs (miRNA) and tRNA-derived fragments (tRF), are known to be involved in post-transcriptional gene regulation. Research has provided evidence that small RNAs may influence immune development in calves. Bovine leukosis is a disease in cattle caused by Bovine Leukemia Virus (BLV) that leads to increased susceptibility to opportunistic pathogens. No research has addressed the potential influence that a maternal BLV infection may have on gene regulation through the differential expression of miRNAs or tRFs in progeny. Blood samples from 14-day old Holstein calves born to BLV-infected dams were collected. Antibodies for BLV were assessed using ELISA and levels of BLV provirus were assessed using qPCR. Total RNA was extracted from whole blood samples for small RNA sequencing. Five miRNAs (bta-miR-1, bta-miR-206, bta-miR-133a, bta-miR-133b, and bta-miR-2450d) and five tRFs (tRF-36-8JZ8RN58X2NF79E, tRF-20-0PF05B2I, tRF-27-W4R951KHZKK, tRF-22-S3M8309NF, and tRF-26-M87SFR2W9J0) were dysregulated in calves born to BLV-infected dams. The miRNAs appear to be involved in the gene regulation of immunological responses and muscle development. The tRF subtypes and parental tRNA profiles in calves born to infected dams appear to be consistent with previous publications in adult cattle with BLV infection. These findings offer insight into how maternal BLV infection status may impact the development of offspring.

Effects of simulated catch-and-release angling of Atlantic salmon shortly before spawning on the viability and development of their offspring

The principle of catch-and-release (C&R) angling is to conserve fish populations while allowing the socioeconomic benefits associated with recreational angling to continue, even at low-stock abundances. We explored how angling-associated parental stress close to spawning could influence early development of the next generation. Wild Atlantic salmon, Salmo salar, were captured on the river Blackwater, N. Scotland, during their spawning migration and exposed to different disturbance protocols intended to simulate C&R angling. Experimental fish were mated with non-experimental fish and their offspring were monitored. Mortality was higher in offspring whose parents were air-exposed. Embryos from stressed parents had smaller yolk sacs compared to controls and offspring from air-exposed parents were shorter at first feeding. Most effects were of similar magnitude regardless of the stressed parent's sex and indicated that C&R angling of Atlantic salmon close to spawning could adversely influence the offspring development. These results suggest that consideration must be given to excluding spawning periods from fishing seasons, and highlight the importance of avoiding air exposure for captured fish, as indicated by best practice guidelines.

Results of Preclinical Animal Studies to Evaluate the Effect of Iptacopan on Pregnancy-Related Outcomes

Introduction: Iptacopan is a first-in-class, oral, selective inhibitor of factor B, a key component of the complement system alternative pathway. Inhibition of the complement system represents a potential mechanism for treatment of several complement-driven diseases including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Here, we report results from the preclinical GLP toxicology studies of iptacopan on embryo-fetal development in rats and rabbits and pre- and postnatal development in rats. Methods: In the definitive embryo-fetal development studies,iptacopan was dosed orally via gavage to pregnant rats at 0, 100, 300, and 1000 mg/kg/day (N=24/group) and to pregnant rabbits at doses of 0, 100, 250, and 450 mg/kg/day (N=20/group) during the period of organogenesis (Gestation Day [GD] 6 to 17 and GD7 to 20, respectively). The progress and outcome of pregnancy were evaluated and fetuses were examined for external, visceral, and skeletal abnormalities. In a pre- and postnatal developmental toxicity study in pregnant rats, iptacopan was dosed orally via gavage at 0, 100, 300, and 1000 mg/kg/day (N=22/group) from GD6 to Lactation Day (LD) 21. The untreated offspring were allowed to mature and the effects on development, behavior, and reproductive performance were assessed. Results: In the rat embryo-fetal development study, maternal administration of iptacopan resulted in no adverse clinical observations, no effects on maternal body weights, and no adverse fetal findings. Non-adverse fetal variations of delayed ossification were observed in the skull. Two fetuses in one out of 22 litters at 1000 mg/kg/day had benign cysts on the left side of the parietal region of the head, with no impact on skeletal (skull), CNS (brain), or any other head-based structure. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo-fetal development was 1000 mg/kg/day. In the definitive rabbit embryo-fetal development study, administration of iptacopan caused reduced maternal body weight gain and food consumption at 450 mg/kg/day. There were no treatment-related fetal malformations or variations. The NOAEL was 250 mg/kg/day for maternal toxicity and 450 mg/kg/day for embryo-fetal development. In the pre- and postnatal development study, no adverse findings were observed in the mated female rats during gestation, parturition, and lactation and there were no adverse effects on development of their offspring, including survival, physical development, behavior, and reproductive performance. The NOAEL for maternal (F0 generation) toxicity, maternal performance, and development of the F1 generation offspring was the highest dose of 1000 mg/kg/day. NOAEL and estimated AUC-based safety margins based on total plasma concentrations for all mentioned studies are shown in the Table. Conclusion: In nonclinical reproductive toxicity studies conducted in pregnant rats and rabbits, iptacopan was found to be generally safe with no teratogenic effects in the rat and rabbit. Estimated AUC-based safety margins were >5-fold for all developmental findings compared to exposure at the clinical dose of 200 mg twice daily. While these preclinical data do not provide definitive conclusions or guidance on the use of iptacopan in pregnant women, they do provide reassurance that there is no overt preclinical signal of embryo-fetal toxicity.

Loss of plasticity in maturation timing after ten years of captive spawning in a delta smelt conservation hatchery.

Adaptation to captivity in spawning programs can lead to unintentional consequences, such as domestication that results in reduced fitness in the wild. The timing of sexual maturation has been shown to be a trait under domestication selection in fish hatcheries, which affects a fish's access to mating opportunities and aligning their offspring's development with favorable environmental conditions. Earlier maturing fish may be favored in hatchery settings where managers provide artificially optimal growing conditions, but early maturation may reduce fitness in the wild if, for example, there is a mismatch between timing of reproduction and availability of resources that support recruitment. We investigated patterns of maturation timing in a delta smelt (Hypomesus transpacificus) conservation hatchery by quantifying changes to the median age at maturity since the captive spawning program was initiated in 2008. Over the span of a decade, we observed a small, but significant increase in age at maturity among broodstock by 2.2 weeks. This trait had low heritability and was largely controlled by phenotypic plasticity that was dependent on the time of year fish were born. Fish that were born later in the year matured faster, potentially a carryover from selection favoring synchronous spawning in the wild. However, higher DI (domestication index) fish showed a loss of plasticity, we argue, as a result of hatchery practices that breed individuals past peak periods of female ripeness. Our findings suggest that the hatchery setting has relaxed selection pressures for fish to mature quickly at the end of the year and, consequently, has led to a loss of plasticity in age at maturity. Hatchery fish that are re-introduced in the wild may not be able to align maturation with population peaks if their maturation rates are too slow with reduced plasticity, potentially resulting in lower fitness.

Maternal folic acid supplementation does not impact skeletal muscle function and metabolism in male and female CD-1 mouse offspring.

Folic acid fortification of all white flour, enriched pasta, and cornmeal products became mandatory in Canada to reduce risk of neural tube defects at birth. Furthermore, Health Canada and the Society of Obstetricians and Gynaecologists of Canada recommend women take daily prenatal folic acid supplements in addition to folic acid fortified foods during pregnancy. However, the influence of maternal folic acid supplementation on offspring development, specifically the highly abundant and metabolically active skeletal muscle, is currently unknown. Thus, the purpose of this study was to determine the effect of supplemental folic acid (four times higher than normal dietary consumption), in utero and throughout suckling on muscle size, function, and metabolism in male and female CD-1 mouse offspring. The major findings were that maternal exposure to supplemental folic acid (i) had no impact on postpartum growth rates or muscle mass in female and male offspring, (ii) had no impact on skeletal muscle contractile kinetics in females and male offspring, and (iii) increased maximal phosphofructokinase activity in extensor digitorum longus of female and male offspring. These findings suggest that exposure to folic acid supplementation in utero and throughout suckling at levels four times higher than recommended had minimal effect on skeletal muscle size, function, and metabolism regardless of sex. Future research is needed explore the underlying biological pathways and mechanisms affected by folic acid supplementation during pregnancy and lactation on offspring skeletal muscle tissue, specifically in humans.

Toxicological effects of the Curatella americana extract in embryo development of female pups from diabetic rats

Maternal diabetes can influence the development of offspring during fetal life and postnatally. Curatella americana is a plant used as a menstrual cycle regulator and to prevent diabetes. This study evaluates the effects of C. americana aqueous extract on the estrous cycle and preimplantation embryos of adult female pups from diabetic rats. Female Sprague Dawley newborn rats received Streptozotocin or vehicle (citrate buffer). At adulthood, were submitted to the Oral Glucose Tolerance Test, and mated. The female rats were obtained and were distributed into four experimental groups: OC and OC/T represent female pups of control mothers and received water or plant extract, respectively; OD and OD/T represent female pups of diabetic mothers and received water or plant extract, respectively. The estrous cycle was followed for 10 days, the rats were mated and on gestational day 4 was performed preimplantation embryo analysis. Phenolic composition and biogenic amines in the extract were analyzed about the influence of the thermal process. The female pups from diabetic dams exhibited glucose intolerance, irregular estral cycle and a higher percentage of pre-embryos in delayed development (morula stage). After C. americana treatment, OD/T group no present a regular estrous cycle. Furthermore, the infusion process increases phenolic compounds and biogenic amines levels, which can have anti-estrogenic effect, anticipates the early embryonic development, and impair pre-implantation embryos. Thus, the indiscriminate use of medicinal plants should be avoided in any life phases by women, especially during pregnancy.

Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff.

Subclinical hypothyroidism (SCH) is defined by elevated thyrotropin (TSH) and normal level of thyroxine (T4). The definition of SCH and the cutoff for TSH normality in pregnancy are debated. In the present study, we assess offspring perinatal outcome, anthropometrics and early development in relation to different TSH levels. An observational study with 77 singleton-pregnant women included by thyroid screening before a planned cesarean section. Two TSH-cutoffs (3.0 and 3.7 mIU/L) defined euthyroid and SCH groups, and were applied to evaluate offspring anthropometrics, complication rates (maternal blood loss, Apgar-score, cord arterial-pH, admission to neonatal intensive care unit, perinatal hypoglycemia) and offspring development. Development was evaluated by Bayley-III test in a subsample at age 6months (n=27) and 15months (n=22). Prevalence of SCH was 31.2 % at TSH-cutoff 3.0 mIU/L, and 16.9 % at TSH-cutoff 3.7 mIU/L. No differences in complications and anthropometrics were observed. In Bayley-III tests, cognitive score was decreased at 6 months (p=0.012) and at 15months (p=0.056) by applying TSH-cutoff 3.0 mIU/L. At cutoff 3.7 mIU/L, motor score was decreased at 15months (p=0.020). Male offspring had significantly lower cognitive scores at age 6 and 15months (TSH-cutoff 3.0 mIU/L), and motor scores at age 15months (TSH-cutoff 3.7 mIU/L). The importance of the definition of thyroid normality in pregnancy is underlined. This study suggests that a gender-effect might be present in maternal thyroid disease, and that developmental differences exist if TSH-cutoff is low. Further research is needed.

Associations between parental adherence to healthy lifestyles and cognitive performance in offspring: A prospective cohort study in China.

Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring's cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring's cognitive performance during adolescence and young adulthood in China. We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring's fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018). Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring's healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring's cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring's overall crystallized intelligence. Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring's cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Amniotic fluid cortisol predicts neonatal and infant development in non-stressed rhesus monkeys: Implications for prenatal stress

Prenatal stress adversely affects offspring development, with fetal cortisol (CORT) exposure being a primary hypothesized mechanism for stress-induced developmental deficits. Fetal CORT exposure can be assessed via measurements in amniotic fluid. However, in humans, amniocentesis is typically only performed for clinical reasons such as karyotyping; thus, amniotic fluid CORT cannot be obtained from a random sample. To test the hypothesis that fetal CORT exposure predicts neonatal and infant development in healthy primates, we measured amniotic fluid CORT in N = 18 healthy rhesus macaque (Macaca mulatta) dams (50:50 female:male infants) between 80 and 124 days gestation (mean ± SEM = 98.3 ± 2.9 days out of 165 days gestational length; i.e., second trimester). Maternal hair cortisol concentrations (HCCs) were assessed throughout pregnancy and lactation. Offspring were assessed for physical growth, neurological development, cognitive development, and HCCs across postnatal days 30–180. Controlling for gestational age at amniocentesis, higher amniotic fluid CORT significantly predicted slower infant growth rate (g/day) in the first 30 days (β = −0.19; R2 = 0.71, p = .008), poorer sensorimotor scores on the day 30 neonatal assessment (β = −0.28; R2 = 0.76, p = .015), and longer time to complete training (β = 0.48; R2 = 0.54, p = .026), but better performance (β = 0.91; R2 = 0.60, p = .011) on a discrimination cognitive task at 120–180 days. Amniotic fluid CORT was not associated with maternal or infant HCCs. Although these results are correlative, they raise the intriguing possibility that fetal CORT exposure in non-stress-exposed primates, as measured by amniotic fluid CORT, programs multiple aspects of neonatal and infant development. On the other hand, amniotic fluid CORT may not relate to chronic CORT levels in either mothers or infants when assessed by hair sampling.

The association between maternal prenatal vitamin B12 intake and child cognitive development

Abstract Background Nutrient deficiencies in diet during pregnancy may have an adverse effect on the development of offspring. The association between prenatal vitamin B12 intake and cognitive functioning in children is unclear. Therefore, we examined such association in Czech children. Methods Czech part of European Longitudinal Study of Pregnancy and Childhood is a population-based prospective longitudinal birth cohort study of pregnant women and their children enrolled in 1991-1992. Dietary data was measured at 32 weeks of gestation using 145 items self-reported food frequency questionnaire. Parents reported on their child's speech and language development at 18 months, 3, 5, and 7 years of age (outcomes ranging from n = 1891 to n = 2362), from which single scores for vocabulary, language, early communication, understanding, and intelligibility were calculated. Higher scores indicate better speech and language development. Data were analysed using multiple ordinal and logistic regression models. Results Higher prenatal vitamin B12 intake was associated with higher speech and language test scores in fully adjusted models. Children of mothers with higher B12 intake had increased likelihood of higher scores in vocabulary (OR = 1.06, 95% CI: 1.01; 1.11), language (OR = 1.05, 95% CI: 1.01; 1.10), early communication (OR = 1.06, 95% CI: 1.01; 1.11) and understanding (OR = 1.09, 95% CI: 1.04; 1.14) at 18 months of age. Furthermore, they were more likely to get maximum points in the intelligibility test at age 3 (OR = 1.08, 95% CI: 1.02; 1.14) opposed to children of mothers with lower B12 intake. There were no associations at 5 and 7 years. Conclusions We found consistent and significant associations between prenatal vitamin B12 intake and early speech and language development. The results suggest that a diet during pregnancy low in vitamin B12 may negatively affect children's cognitive development. Thus, a healthy pregnancy diet with sufficient vitamin B12 should be promoted. Key messages • A diet low in vitamin B12 during pregnancy may have negative effects on the cognitive development of offspring, according to a longitudinal birth cohort study. • Adequate prenatal vitamin B12 intake is important for cognitive development, particularly speech and language development.