Development Of Offspring Research Articles

Bisphenol F (BPF) exposure impairs sperm quality and offspring development in male zebrafish.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is widely used in consumer products, increasing the potential for environmental exposure. Our study investigated the reproductive effects of BPF on adult male zebrafish and explored its toxicological mechanisms, as well as its intergenerational effects. Adult male zebrafish were exposed to BPF concentrations of 0, 50, 500, 2500, and 5000 nM for 21 days. We evaluated sperm cell quantity and quality, hormonal markers testosterone (T) and vitellogenin (VTG), gene expression profiles related to hormone synthesis, metabolism, apoptosis, cell cycle, sexual behavior, and offspring health metrics including survival, development and locomotion. BPF exposure did not significantly affect body weight or gonadal index. However, at 500 and 2500 nM, a significant reduction in sperm count was observed. BPF exposure led to decreased serum T and increased hepatic VTG levels, indicating hormonal disruption. At 50 nM, BPF initiated sperm apoptosis, and at higher doses, it disrupted sperm meiosis, affecting cell distribution. This exposure negatively impacted sperm quality, reduced offspring survival rates, and altered sperm motility in adult fish. Offspring from BPF-exposed groups showed developmental issues, including increased mortality, delayed developmental stages, abnormal tail coiling and heart rate, which correlated with paternal sperm count and quality changes, alterations in T and VTG levels, and cell cycle phase distributions. Our study demonstrated that BPF exposure significantly impacted sperm quality, characterized by reduced sperm count and altered motility patterns, leading to developmental anomalies in offspring. These novel findings highlight the need for further research into BPF's reproductive and developmental toxicity, emphasizing the potential risks to aquatic ecosystems and human health. The observed effects on sperm quality, hormonal balance, and offspring development provide new insights into the reproductive toxicity profile of BPF.

Comparison of Acute and Protracted Gamma Irradiation Effects During Perinatal Development in Beagle Dogs.

Ionizing radiation exposure during perinatal development can produce various biological effects on the developing offspring. These effects are dependent on a number of factors, including total dose, dose rate and the developmental processes occurring at the time of irradiation. The present study conducted an analysis of historical radiobiological archived data involving 60Co-gamma irradiation of beagle dogs at specific periods of prenatal or postnatal development. The original studies were performed at two sites where animals were exposed to a single, acute dose of 0.2 or 1.0 Gy at six different stages of perinatal development or with protracted exposures ranging from 0.004 to 0.35 Gy per day, over multiple days of gestation. A number of outcomes were investigated after perinatal irradiation including changes in sex ratio, survival probability, disease incidence and growth of animals, based on collected size and weight measurements of animals and different tissues. Protracted irradiations with doses up to 0.35 Gy per day did not significantly affect survival in animals when irradiated prenatally, although significant increases in the incidence of neoplasms and diseases related to the cardiovascular and urogenital system were observed at the time of death. Dogs irradiated at a dose rate of 0.10 Gy per day, with the irradiations continuing after birth and resulting in the accumulation of large total doses, were observed to have chronic radiation syndrome symptoms based on pathologies related to the hematopoietic system. Acute irradiation with 0.2 and 1.0 Gy resulted in changes of different body or tissue sizes measured in animals terminally, with changes detected after irradiation at all tested prenatal and postnatal time points, with the exception of irradiation at 365 days after birth. The present analysis provides new information regarding the biological effects of ionizing radiation during perinatal development in offspring in the unique mammalian study model of the beagle dog.

The Impact of Maternal Chronic Inflammatory Conditions on Breast Milk Composition: Possible Influence on Offspring Metabolic Programming

Breastfeeding is the best way to provide newborns with crucial nutrients and produce a unique bond between mother and child. Breast milk is rich in nutritious and non-nutritive bioactive components, such as immune cells, cytokines, chemokines, immunoglobulins, hormones, fatty acids, and other constituents. Maternal effects during gestation and lactation can alter these components, influencing offspring outcomes. Chronic inflammatory maternal conditions, such as obesity, diabetes, and hypertension, impact breast milk composition. Breast milk from obese mothers exhibits changes in fat content, cytokine levels, and hormonal concentrations, potentially affecting infant growth and health. Similarly, diabetes alters the composition of breast milk, impacting immune factors and metabolic markers. Other pro-inflammatory conditions, such as dyslipidemia and metabolic syndrome, have been barely studied. Thus, maternal obesity, diabetes, and altered tension parameters have been described as modifying the composition of breast milk in its macronutrients and other important biomolecules, likely affecting the offspring’s weight. This review emphasizes the impact of chronic inflammatory conditions on breast milk composition and its potential implications for offspring development through the revision of full-access original articles.

Mother-infant stress contagion? Effects of an acute maternal stressor on maternal caregiving behavior and infant cortisol and crying.

Postpartum maternal distress has been associated with adverse infant outcomes. A potential pathway of how maternal distress affects infant outcomes could be alterations in maternal caregiving behavior. However, the associations between maternal distress, caregiving behavior, and infant outcomes have never been tested in a controlled experiment. This preregistered study utilized an experimental design to investigate the effects of an acute maternal stressor on infant cortisol and crying and the possible mediating role of maternal caregiving behavior. Mother-infant dyads (N = 91) participated in a lab visit at 8 weeks postpartum, where mothers were separated from their infants to either perform a Trier Social Stress Test (TSST) or a control task. The task was immediately followed by a mother-infant interaction to assess maternal caregiving behavior and infant cortisol and crying. Our structural equation model found no differences between conditions (stressor/control) on maternal caregiving behavior and infant response to maternal stress. Secondary findings revealed that higher quality of maternal caregiving behavior was related to lower levels of infant crying and lower cortisol levels at the end of the visit, but not cortisol at reunion. Our findings do not support the occurrence of mother-infant stress contagion in this experimental setting but do indicate a link between maternal caregiving behavior and infant behavioral and cortisol responses. Given the high prevalence of maternal mental health problems and their possible negative association with offspring development, further (experimental) research is needed to understand just how maternal postpartum distress affects young infants.

Prenatal maternal stress: triangulating evidence for intrauterine exposure effects on birth and early childhood outcomes across multiple approaches

BackgroundMaternal stress during pregnancy may impact offspring development via changes in the intrauterine environment. However, genetic and environmental factors shared between mothers and children might skew our understanding of this pathway. This study assesses whether prenatal maternal stress has causal links to offspring outcomes: birthweight, gestational age, or emotional and behavioral difficulties, triangulating across methods that account for various measured and unmeasured confounders.MethodsWe used data from the Norwegian Mother, Father, and Child Cohort Study (MoBa), including maternal reports on prenatal stress at work, at home, and via stressful life events as exposures. Outcomes were children’s birthweight and gestational age, from the Medical Birth Registry of Norway, and maternal reports on early offspring emotional and behavioral difficulties. We assessed associations using four approaches: sibling control analyses, gene-environment interaction analyses, intergenerational Mendelian randomization (MR), and negative control (i.e., postnatal stress) analyses.ResultsMaternal prenatal stress was observationally associated with offspring lower birthweight (e.g., βwork = − 0.01 [95%CI: − 0.02, − 0.01]), earlier birth (e.g., βwork = − 0.04 [95%CI: − 0.04, − 0.03])), and more emotional (e.g., βevents = 0.08 [95%CI: 0.07, 0.09]) and behavioral difficulties (e.g., βrelationship = 0.08 [95%CI: 0.07, 0.09]) in the full sample (N = 112,784). However, sibling control analyses (N = 36,511) revealed substantial attenuation of all associations after accounting for familial factors. Gene-environment interaction models (N = 76,288) showed no clear evidence of moderation of associations by mothers’ polygenic scores for traits linked to stress sensitivity. Intergenerational MR analyses (N = 29,288) showed no clear evidence of causal effects of maternal plasma cortisol on any offspring outcomes. Negative control exposure analyses revealed similar effect sizes whether exposures were measured prenatally or postnatally.ConclusionsOur results indicate that links between prenatal maternal stress and variation in early offspring outcomes are more likely to be confounded than causal. While no observational study can rule out causality, the consistency of our findings across different approaches is striking. Other sources of prenatal stress or more extreme levels may represent intrauterine causal risk factors for offspring development. Nonetheless, our research contributes to identifying boundary conditions of the fetal programming and developmental origins of health and disease hypotheses, which may not be as universal as sometimes assumed.

Sex-specific reproductive toxicity of subacute exposure to glufosinate-ammonium in zebrafish (Danio rerio).

Glufosinate-ammonium (GLA) is a common agricultural herbicide used worldwide. It can be transported into water bodies and can persist for long periods, posing a risk to non-target aquatic organisms. In this study, adult zebrafish were exposed to GLA (0, 0.6, 6, and 60mg/L) for 21days to evaluate its effect on reproduction. Fecundity, offspring development, sex hormone levels, histological changes, and apoptosis in the gonads were measured, and the expression levels of genes related to the hypothalamic-pituitary-gonadal-liver (HPG-L) axis, the cell cycle, and apoptosis were examined to assess the toxic mechanisms of GLA. Higher GLA concentrations were measured in the ovaries than in the testes. Decreases in spawning count, sperm density, and motility were observed. Meanwhile, the offspring survival rate decreased, and larval offspring swimming behavior was inhibited. GLA exposure significantly increased estradiol levels in females and reduced testosterone levels in males by affecting the expression of HPG-L axis genes. Furthermore, GLA exposure induced apoptosis in gonadal cells by controlling the expression of genes involved in cell cycle regulation and apoptotic pathways. Notably, the smaller effects of GLA concentration on body weight, gonad somatic index value, gonadal cell composition, and gonadal cell apoptosis were observed in male fish than in female fish. Taken together, GLA can accumulate in the gonads and cause sex-specific alterations in the expression of genes involved in the HPG-L axis and subsequent steroidogenesis and gametogenesis, which may be responsible for GLA-induced reproductive and developmental toxicities.

Impact of microplastics on female reproductive health: insights from animal and human experimental studies: a systematic review.

This systematic review aims to evaluate the impact of microplastics on female reproductive health by analyzing experimental studies. A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases to identify experimental studies published between 2021 and 2023. Studies investigating the effects of microplastics on reproductive organs, hormone levels, fertility rates, and offspring development in female subjects were included. The quality of the studies was assessed using the Cochrane risk of bias tool. A total of 15 studies met the inclusion criteria. The results indicate that exposure to microplastics significantly affects ovarian function, decreases fertility rates, and disrupts hormone levels in female subjects. Several studies also reported negative effects on embryo development and offsprings health. The quality of the studies varied, with some showing a high risk of bias. The evidence from experimental studies suggests that microplastics have a detrimental effect on female reproductive health. However, the variation in study quality highlights the need for more rigorous research to confirm these results and better understand the underlying mechanisms.

The mediating role of maternal fasting plasma glucose level and lipid levels in the third trimester of pregnancy between pre-pregnancy BMI and offspring physical development at birth.

The findings of the study indicate that pre-pregnancy BMI is associated with offspring's physical development at birth, with the overweight or obese pre-pregnancy BMI group having an increased risk of macrosomia. The most effective prediction for macrosomia comes from a combination of BMI, FPG, TG, and HDL-C levels. Moreover, the influence of pre-pregnancy BMI on offspring's physical development is partially mediated by FPG, TG, and HDL-C. • Previous research has established correlations between pre-pregnancy BMI and offspring's physical development. • Previous studies have demonstrated that late pregnancy blood lipid and glucose levels significantly predict fetal physical development. • The combination of pre-pregnancy BMI, FPG, TG, and HDL-C is the most effective predictor of macrosomia. • FPG, TG, and HDL-C jointly mediate the effect of pre-pregnancy BMI on physical growth.

Maternal Gut Inflammation Aggravates Acute Liver Failure Through Facilitating Ferroptosis via Altering Gut Microbial Metabolism in Offspring.

Microbial transmission from mother to infant is important for offspring microbiome formation and health. However, it is unclear whether maternal gut inflammation (MGI) during lactation influences mother-to-infant microbial transmission and offspring microbiota and disease susceptibility. In this study, it is found that MGI during lactation altered the gut microbiota of suckling pups by shaping the maternal microbiota in the gut and mammary glands. MGI-induced changes in the gut microbiota of suckling pups lasted into adulthood, resulting in the exacerbation of acute liver failure (ALF) caused by acetaminophen (APAP) in offspring. Specifically, MGI reduced the abundance of Lactobacillus reuteri (L. reuteri) and its metabolite indole-3-acetic acid (IAA) level in adult offspring. L. reuteri and IAA alleviated ALF in mice by promoting intestinal IL-22 production. Mechanistically, IL-22 limits APAP-induced excessive oxidative stress and ferroptosis by activating STAT3. The intestinal abundances of L. reuteri and IAA are inversely associated with the progression of patients with ALF. Overall, the study reveals the role of MGI in mother-to-infant microbial transmission and disease development in offspring, highlighting potential strategies for intervention in ALF based on the IAA-IL-22-STAT3 axis.

Potential Health Risks of Exposure to Graphene and Its Derivatives: A Review

Graphene and its derivatives (GDs) have been applied in many fields, like photocatalysts, sensors, and biomedical delivery, due to its excellent physicochemical properties. However, the widespread use of GDs has significantly increased human exposure to these materials. Some health risks of exposure to GDs have been identified, including organ fibrosis, inflammation, DNA damage, etc. Given that graphene is a novel concern, we especially emphasized the various exposure pathways and potential health risks of exposure to GDs. People get exposed to GDs mainly through inhalation, ingestion, dermal contact, etc. GDs could transfer to the circular system of people and accumulate in blood, cells, and major organs. GDs exposure could induce organ and cell inflammatory responses and damage, such as disrupted kidney function, declined cell vitality, cytotoxicity, etc. These changes at the organ and cell levels might lead to adverse tangible influences on people, like decreased locomotor activity, the accelerated aging process, and even abnormal offspring development. We also summarized the characterization and detection methods of GDs. In addition, we compared the studies of exposure to dust and GDs in the aspects of health risks and study methods. This review could offer a comprehensive summary related to GDs and provide helpful references for further graphene-related studies.

Insights into organophosphorus insecticide malathion induced reproductive toxicity and intergenerational effect in zebrafish (Danio rerio).

The reproductive and transgenerational effects of malathion, a widely utilized low-toxicity organophosphorus insecticide, were explored using zebrafish as model animal. Adult zebrafish (F0) were exposed to malathion at 0.1-1.0mg/L for 60days for exploring the reproductive toxicity in sex differences and the potential mechanisms, and development and transcription levels in F1 offspring were assessed. Malathion significantly suppressed the fertility of zebrafish as evidenced by reduced spawning and lower fertilization rates in F1 offspring. Abnormal gonadal development and steroid hormone disorders were observed in F0 zebrafish, which was associated with the alterations in the transcription of core genes (such as cyp11a, cyp19a, vtg1, era) along the hypothalamus-pituitary-gonad-liver (HPGL) axis. The expression level of vtg1 played a key role in the malathion-induced sex dependence on E2 and VTG levels. The reduction of E2 and VTG could disrupt ovarian capability in females. E2 excess would cause feminization in males. Molecular docking indicated that reproductive disorders induced by malathion in zebrafish mainly through estrogen-like effects and CYP11A antagonism. Parental exposure to malathion abnormalized embryonic development in F1 offspring, comprising heartbeats decrease, deformities and body length reduction. Transcriptomics suggested that malathion-induced reproductive toxicity could be transmitted across generations, which may adversely affect fish populations.

Associations between maternal fish intake and polyunsaturated fatty acid status with childhood asthma in a high fish-eating population.

Studies investigating associations between prenatal polyunsaturated fatty acid status (PUFAs), in particular the anti-inflammatory n-3 PUFAs, and the development of childhood asthma have yielded conflicting results. To determine the associations between maternal fish intake (a rich source of the n-3 PUFAs), maternal or cord PUFAs with the prevalence of childhood asthma in a high fish-eating population. We examined these associations between fish intake and PUFA concentrations with childhood asthma prevalence in the Seychelles Child Development Study Nutrition Cohort 2, a large observational study in a high fish-eating population. Maternal fish intake during pregnancy and child's fish intake at 7 years were assessed by questionnaire, with frequency reported as meals/week. Serum concentrations of PUFAs were quantified in maternal blood collected at 28 weeks' gestation (n = 1448) and in cord blood (n = 1088). Asthma in children at 7 years was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire (n = 1098). A total of 97 children (10.5%) were reported to have asthma. In regression analysis, the odds of childhood asthma were not associated with maternal fish intake or maternal PUFA status. Cord DHA concentrations were associated with increased asthma prevalence when the highest quartile (≥0.123 mg/mL) was compared with the lowest (<0.061 mg/mL). The results from this current study add to the growing body of evidence that fish consumption during pregnancy is not associated with asthma development in offspring. The associations between cord blood DHA and asthma prevalence are unexpected and warrant further investigation.

Oral administration of cyantraniliprole to wistar rats during pregnancy and lactation alters maternal behavior and harms the female reproductive system of pubertal and adult offspring.

Over the past years, global pesticide use has increased by 20%. New insecticidal molecules, like cyantraniliprole, aim to reduce side effects due to the high toxicity of pesticides and their harmful effects on health and the environment. Its mechanism involves binding to ryanodine receptors, causing rapid calcium ion release. As a new molecule, studies on its effects on mammals are scarce. This work evaluates oral cyantraniliprole's impacts during pregnancy and lactation on maternal behavior and the reproductive system of female offspring. Approved by CEUA-UEL (OF. CIRC. CEUA n. 20/2020), Wistar rats were mated, and after pregnancy diagnosis, divided into control groups, C1, C10, and C150, receiving water and cyantraniliprole at 1, 10, and 150mg/kg/day, respectively, by gavage. Maternal behavior, offspring physical development, uterine and ovarian histology, and oxidative stress levels were analyzed. Maternal exposure to 150mg/kg/day was toxic to pregnancy, causing loss of the experimental group. Analysis showed significant changes in maternal behavior in C1 and C10, with increased pup contact, longer breastfeeding, and less cleaning time. No changes in offspring development were observed in C1 and C10. Histology and oxidative stress analysis of the ovaries showed no changes, while uterine analysis indicated thickening and increased oxidative stress.

Reproductive toxicity and transgenerational effects of co-exposure to polystyrene microplastics and arsenic in zebrafish.

Microplastics (MPs) are ubiquitous environmental pollutants that have garnered significant attention due to their small particle size, resistance to degradation and large specific surface area, which makes it easy to adsorb various pollutants, particularly heavy metals. Arsenic (As), a common metal poisons, poses significant risks due to its widespread industrial use. When MPs and As co-exist in the environment, they can exert combined toxic effects on organisms, affecting various systems, including the nervous system. However, research on the reproductive damage caused by the co-exposure to MPs and As is limited, and the toxic effects and mechanisms remain unclear. In this study, we investigated the co-exposure of polystyrene microplastics (PSMP) and As on female zebrafish to evaluate the reproductive toxicity and transgenerational effects. The results revealed that the combined exposure exhibited elevated reproductive toxicity, resulting in reduced gonadal indices, abnormal oocyte maturation, and disrupted sex hormone levels, as evidenced by an increased E2/T ratio. Metabolomics analyses revealed that the co-exposure to PSMP and As primarily affected pathways involved in aminoacyl-tRNA biosynthesis, sphingolipid metabolism, linoleic acid metabolism, galactose metabolism, and amino sugar and nucleotide sugar metabolism. These pathways are associated with oxidative stress, lipid synthesis, and sex hormone synthesis. Importantly, the combined exposure group exhibited more pronounced effects on offspring development compared to the alone treatment group, characterized by increased mortality rate, decreased hatching rate, and reduced heart rate. These findings provide evidence that co-exposure to MPs and As damages the reproductive system and adversely affects offspring growth and development.

Defective Hippocampal Primary Ciliary Function and Aberrant LKB1/AMPK Signaling Pathway Are Associated With the Inhibition of Autophagic Activity in Offspring Born to Mothers of Advanced Maternal Age.

Advanced maternal age (AMA) negatively influences the development and cognitive functions of offspring. However, the underlying mechanism remains to be elucidated. As hippocampal autophagy and primary cilia play a crucial role in learning and memory abilities, this study aimed to investigate the effects of AMA on hippocampal autophagy and primary cilia, and to explore their relationship with the changes of LKB1/AMPK signaling pathway in offspring rats. The whole brains and hippocampus of offspring born to 12-month-old (AMA) and 3-month-old (control) Sprague-Dawley (SD) female rats were collected on post-natal days (P) 14, 28, and 60. Transmission electron microscopy was employed to count the number of autophagosomes. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to quantify gene expression, and immunofluorescence was used to measure primary cilia. The results revealed that autophagic activity was inhibited from childhood to adulthood in the AMA group. Furthermore, in the early developmental stage, primary ciliogenesis and growth in the hippocampus in the AMA group were impaired, with astrocytes being more severely affected. In addition, the AMA group exhibited an abnormal activation of the LKB1/AMPK signaling pathway. Thus, in offspring born to mothers of AMA, impaired hippocampal primary ciliary function and aberrant activation of the LKB1/AMPK signaling pathway are associated with inhibited autophagic activity.

Effect of Bisphenol F on Reproductive Function in F1 Generation Male Mice and its Potential Mechanisms.

Bisphenol F (BPF) is an environmental endocrine disruptor capable of crossing the placental barrier and affecting the growth and development of offspring. Despite its potential impact, systematic research about effects of BPF on the reproductive function of male offspring remains limited. In this study, pregnant female mice were exposed to BPF at doses of 40, 400, and 4000 μg/kg during gestation and lactation, respectively, to evaluate its impact on testicular damage, testosterone levels, and spermatogenesis of male offspring (F1 generation), and further explore the mechanisms using transcriptomics. First, the study demonstrated that BPF induces testicular damage in F1 generation mice, leading to decreased testosterone levels and sperm quality. Second, transcriptomic analysis revealed that BPF affected spermatogenesis in F1 generation mice by disrupting retinol metabolism. Third, transcriptomic analysis revealed that BPF reduce the capacity for testosterone synthesis in F1 generation mice by diverting the testosterone precursor dehydroepiandrosterone (DHEA) towards the synthesis of 16α-hydroxydehydroepiandrosterone rather than testosterone. Finally, it was confirmed that BPF hinder cholesterol transport to mitochondria by inhibiting the cAMP signaling pathway, thereby impacting testosterone synthesis. In summary, the results of this study suggest that gestational exposure to BPF can lead to reproductive dysfunction in F1 generation male mice.

Supplementation with probiotics co-cultivation improves the reproductive performance in a sow-piglet model by mother-infant microbiota transmission and placental mTOR signaling.

Maternal nutritional supplementation has a profound effect on the growth and development of offspring. FAM® is produced by co-cultivation of Lactobacillus acidophilus and Bacillus subtilis and has been demonstrated to potentially alleviate diarrhea, improve growth performance and the intestinal barrier integrity of weaned piglets. This study aimed to explore how maternal FAM improves the reproductive performance through mother-infant microbiota, colostrum and placenta. A total of 40 pregnant sows (Landrace × Large White) on d 85 of gestation with a similar parity were randomly divided into two groups (n = 20): the control group (Con, basal diet) and the FAM group (FAM, basal diet supplemented with 0.2% FAM). The experimental period was from d 85 of gestation to d 21 of lactation. The results revealed that maternal supplementation with FAM significantly decreased the number of weak-born litters and the incidence of diarrhea, as well as increasing birth weight and average weaning weight, accompanied by increased levels of colostrum nutrient composition and immunoglobulins. In addition, FAM modulated the structure of mother-infant microbiota and promoted the vertical transmission of beneficial bacteria, such as Verrucomicrobiota and Akkermansia. Furthermore, FAM contributed to improving the expression of GLU and AA transporters in the placenta, and increasing the activity of the mTOR signaling pathway. Collectively, maternal supplementation with FAM during late pregnancy and lactation could improve reproductive performance through the transmission of beneficial mother-infant microbiota and placental mTOR signaling pathway and promote fetal development.

Prenatal Exposure to Dibutyl Phthalate and Its Negative Health Effects on Offspring: In Vivo and Epidemiological Studies.

Dibutyl phthalate (DBP) is a low-molecular-weight phthalate commonly found in personal care products, such as perfumes, aftershaves, and nail care items, as well as in children's toys, pharmaceuticals, and food products. It is used to improve flexibility, make polymer products soft and malleable, and as solvents and stabilizers in personal care products. Pregnancy represents a critical period during which both the mother and the developing embryo can be significantly impacted by exposure to endocrine disruptors. This article aims to elucidate the effects of prenatal exposure to DBP on the health and development of offspring, particularly on the reproductive, neurological, metabolic, renal, and digestive systems. Extensive research has examined the effects of DBP on the male reproductive system, where exposure is linked to decreased testosterone levels, reduced anogenital distance, and male infertility. In terms of the female reproductive system, DBP has been shown to elevate serum estradiol and progesterone levels, potentially compromising egg quality. Furthermore, exposure to this phthalate adversely affects neurodevelopment and is associated with obesity, metabolic disorders, and conditions such as hypospadias. These findings highlight how urgently stronger laws prohibiting the use of phthalates during pregnancy are needed to lower the risks to the fetus's health and the child's development.

Evaluation of the effect of rozanolixizumab on pregnancy outcomes and pre- and postnatal development in cynomolgus monkeys.

Rozanolixizumab, a humanised immunoglobulin (Ig) G4 monoclonal antibody that selectively inhibits binding of IgG to the neonatal Fc receptor (FcRn), was evaluated in an embryo-foetal enhanced pre- and postnatal development (ePPND) study. Pregnant female cynomolgus monkeys (19 per group) received subcutaneous rozanolixizumab 50mg/kg or 150mg/kg or vehicle every 3 days from gestation day 20 until delivery. The proportion of pregnancy losses was 15.8%, 21.1% and 5.3%, in the rozanolixizumab 50mg/kg, 150mg/kg and control groups, respectively. Based on eNormograms for groups of 18 or 20 animals, these results were considered to be within the range of spontaneous prenatal losses naturally observed in cynomolgus monkeys. Foetal examinations revealed no treatment-related effects. All infants had normal postnatal development, although higher mortality was observed in female infants from the control group during the first 3 weeks. All infants were able to mount a normal immune response to keyhole limpet haemocyanin when vaccinated at the age of 4 months. Offspring from 150mg/kg-treated mothers had very low IgG levels at birth, indicating blockade of maternal IgG transfer; infants from mothers who received 50mg/kg had variable IgG levels at birth, with mothers who had developed significant anti-drug antibodies conferring maternal IgG transfer to varying degrees. Rates of infection in infants were similar across treatment groups. IgG levels in infants from rozanolixizumab-treated groups normalised within 2 months. Treatment of pregnant cynomolgus monkeys with the FcRn inhibitor rozanolixizumab had no adverse effects on pre- or postnatal development of offspring, including immune system development.

Effects of periodontal disease on the reproductive performance and offspring of Wistar rats.

Periodontitis can induce systemic inflammation, and it may affect the testicles and male reproductive performance. This study investigated the effects of periodontitis on the testicles, reproductive performance, and offspring development in male rats. Male Wistar rats were induced with periodontitis by ligating their first molars. After 14 days of inducing periodontal lesions, the animals were observed for an additional 54 days, corresponding to a complete cycle of spermatogenesis. Rats from the periodontitis group (GP, n=12) and the control group (GC, n=12) were paired with healthy females (n=48) for 10 days, equivalent to 2 estrous cycles. Post-mating, the males underwent microtomographic, histological, and reproductive parameter assessments. Microtomographic analysis revealed higher porosity around the first molar in GP (26±6%) and greater distance between the amelocemental junction and the alveolar bone (1.37 [1.12-1.90] mm), indicative of bone resorption. GP also exhibited significant decreases in final body weight, reduced Sertoli and Leydig cell counts, and lowered testosterone levels compared to GC. Significant morphological alterations in sperm tails were observed in GP compared to GC. Periodontitis adversely affected reproductive performance, evoking, and offspring development in male rats. These findings highlight the systemic impacts of periodontal disease on male reproductive health in an animal model. Our study investigated how periodontitis can affect male reproductive health in rats and offspring development. We induced periodontitis in male rats and, after a full cycle of sperm production, these rats were mated with healthy females. We observed that the rats with periodontitis had worse reproductive performance compared to the control group without periodontitis. Additionally, the offspring of the rats with periodontitis showed signs of compromised intrauterine development and a higher incidence of congenital malformations. These results highlight that the inflammation caused by periodontitis can have adverse effects beyond the mouth, significantly impacting male reproductive health and offspring development. These findings suggest the need for further research into the clinical implications of periodontitis on reproductive health.