F1 Females Research Articles

Growth Performance, Body Measurements and Live Weight Estimation of Tülü (Bactrian × Dromedary F1) Calves from Birth to Six Months of Age

A hybrid camel Tülü (Bactrian male x Dromedary female F1) males are preferred in camel wrestling, which is a culture unique to Anatolia. In this study, changes of live weight (LW), daily weight gain (DWG), and body measurements (BMs) of Tülü calves in the first 6 months of age in a farm in Aydın province, Türkiye, were determined as well as developing equations to estimate LW from body measurements. Tülü calves average birth weight (BW) was 34.7±1.80 kg and reached 175.3±3.38 kg at the age of 6 months with a 0.768±0.03 kg DWG during this time. Although the monthly total weight gains and monthly DWG averages of the calves in the first 6 months were similar, the changes in monthly LW and BMs were statistically significant (P<0.01). Abdominal girth (AG) alone can be used to predict LW in the analysis performed to estimate LW from body measurements by stepwise regression (R²=95.62%). In conclusion, Tülü calves had relatively high growth rate in their first six months of age, and unlike other livestock species, instead of hearth girth (HG), AG that includes the hump can be used to estimate LW of Tülü calves.

Fluoride-Induced Autophagy and Apoptosis in the Mouse Ovary: Genomic Insights into IL-17 Signaling and Gut Microbiota Dysbiosis.

Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice. To explore these mechanisms, F0 pregnant mice were exposed to deionized water (control) or 100 mg/L sodium fluoride (NaF) during gestation and throughout the F1 generation (n = 16 females/group), covering puberty to weaning and maturity. NaF exposure caused significant reductions in body weight, organ coefficients, and pathological indices, with increased ovarian autophagic vacuoles, mitochondrial injuries, and elevated serum/ovary LPS levels in F1 females. qRT-PCR, fluorescent staining, biochemical assays, and Western blotting confirmed the activation of IL-17 signaling, apoptosis, and autophagy. Moreover, 16S rRNA sequencing revealed gut microbiota dysbiosis in NaF-exposed F1 females, potentially exacerbating ovary injury via serum LPS elevation. The gut dysbiosis could justify deteriorated serum LPS levels and its connection to F-induced ovary injury. These findings provide mechanistic insights into fluoride-induced reprotoxicity, emphasizing the interplay of IL-17 signaling, autophagy, and apoptosis in disrupting cellular homeostasis and suggesting potential therapeutic targets.

Diet-Induced Obesity in the Rat Impairs Sphingolipid Metabolism in the Brain and This Metabolic Dysfunction Is Transmitted to the Offspring via Both the Maternal and the Paternal Lineage.

Obesity leads to a number of health problems, including learning and memory deficits that can be passed on to the offspring via a developmental programming process. However, the mechanisms involved in the deleterious effects of obesity on cognition remain largely unknown. This study aimed to assess the impact of obesity on the production of sphingolipids (ceramides and sphingomyelins) in the brain and its relationship with the learning deficits displayed by obese individuals. We also sought to determine whether the effects of obesity on brain sphingolipid synthesis could be passed on to the offspring. Learning abilities and brain concentration of sphingolipids in male and female control and obese founder rats (F0) and their offspring (F1) were evaluated, respectively, by the novel object recognition test and by ultra-performance liquid chromatography tandem mass spectrometry. In addition, a global lipidome profiling of the cerebral cortex and hippocampus was performed. Both male and female F0 rats showed impaired learning and increased concentrations of ceramides and sphingomyelins in the hippocampus and frontal cortex compared to their control counterparts. However, the overall lipidome profile of these brain regions did not change with obesity. Remarkably, the alterations in brain sphingolipid synthesis, as well as the cognitive impairment induced by obesity, were also present in adult F1 male rats born to obese mothers or sired by obese fathers and were associated with enhanced expression of mRNAs coding for enzymes involved in the de novo synthesis of ceramides. These results show that the cognitive deficits and impaired sphingolipid metabolism induced by obesity can be transmitted to the offspring through both the maternal and paternal lineages and suggest that an increase in the brain concentration of sphingolipids could play a causal role in the cognitive deficits associated with obesity.

Prenatal exposure to diethylstilbestrol has multigenerational effects on folliculogenesis

Diethylstilbestrol (DES) is an estrogenic endocrine disrupting chemical (EDC) that was prescribed to millions of pregnant women worldwide, leading to increased rates of infertility in the exposed offspring. We have previously demonstrated that this reduced fertility persists for multiple generations in the mouse. However, how altered ovarian function contributes to this infertility is unknown. Therefore, this study sought to determine if DES exposure promotes two common ovarian disorders, primary ovarian insufficiency (POI) and polycystic ovary syndrome, contributing to the reduced fertility in DES offspring. Moreover, we investigated if these impacts are transgenerational. Gestating mice were exposed to 100 µg/kg DES, and ovarian morphology was observed in F1-F3 female descendants. F1 females trended towards fewer primordial and more secondary follicles and similarly, F2 females had fewer primordial and significantly more secondary follicles compared to controls. No differences in follicle proportions were observed in the F3. Moreover, DES exposure did not increase follicular cysts. These results show that DES accelerates folliculogenesis, indicative of a POI phenotype and that this is likely contributing to the reduced fertility observed in DES descendants. Moreover, this study highlights the ability of estrogenic EDCs to disrupt folliculogenesis, which may exacerbate the onset of POI in women already at risk.

Acephate Exposure Induces Transgenerational Ovarian Developmental Toxicity by Altering the Expression of Follicular Growth Markers in Female Rats.

Acephate is an organophosphate foliar and soil insecticide that is used worldwide. In this study, the transgenerational ovarian developmental toxicity caused by acephate, along with its in utero reprogramming mechanisms, were explored. Thirty female virgin Wistar albino rats were randomly assigned to three groups: one control group and two acephate treatment groups. The treatment groups received daily low or high doses of acephate (34.2 mg/kg or 68.5 mg/kg body weight, respectively) from gestational day 6 until spontaneous labor, resulting in F1 offspring. At 28 days, a subgroup of F1 females were euthanized. The ovaries were extracted, thoroughly cleaned, and weighed before being fixed for further analysis. The remaining F1 females were mated with normal males to produce the F2 generation. The F1 female offspring presented reduced fertility and body weight, whereas the ovarian weight index and sex ratio increased in a dose-dependent manner. Structural analysis revealed altered follicular abnormalities with ovarian cells displaying pyknotic nuclei. Additionally, the gene and protein expression of Cyp19 decreased, whereas that of Gdf-9 increased in the high-dose treatment group (68.5 mg/kg). We also observed significantly increased expression levels of ovarian estrogen receptor 1 (Esr1) and insulin-like growth factor 1 (Igf1), whereas Insl3 expression was significantly decreased. The F2 female offspring presented reproductive phenotype alterations similar to those of F1 females including decreased fertility, reduced Cyp19 gene and protein expression, and structural ovarian abnormalities similar to those of polycystic ovary syndrome (PCOS). In conclusion, acephate induced ovarian developmental toxicity across two generations of rats, which may be linked to changes in the ovarian Cyp19, Gdf9, Insl3, and Igf1 levels.

Maternal exposure to buprenorphine, but not methadone, during pregnancy reduces social play behavior across two generations of offspring.

The prevalence of newborns exposed to medications for opioid use disorder (MOUD), such as methadone or buprenorphine, during pregnancy is increasing. The opioid system plays a crucial role in regulating and shaping social behavior, and children prenatally exposed to opioids face an increased risk of developing behavioral problems. However, the impact of prenatal exposure to MOUD on offspring's social behavior during adolescence and adulthood, as well as potential intergenerational effects, remains largely unexplored. Our study employed a translationally relevant animal model to investigate how maternal (F0) exposure to MOUD during pregnancy affects social behavior in young and adult rats across the first (F1) and second (F2) generation of offspring. Female Sprague-Dawley rats were implanted with an osmotic minipump delivering methadone (10mg/kg/day), buprenorphine (1mg/kg/day), or sterile water, prior to mating with drug-naïve males. Adult F1 females were mated with treatment-matched F1 males to generate F2 offspring. We assessed social play behavior in juvenile offspring, and social interaction behavior in a three-chamber social interaction test in young adults of the F1 and F2 generations. Maternal exposure to buprenorphine, but not methadone, during pregnancy reduced social play behavior in both F1 and F2 offspring, expressed by a reduced number of pounces and pins, which are the two most characteristic parameters of social play in rats. Adult social interactions were unaffected by prenatal MOUD exposure across both generations. Maternal exposure to buprenorphine during pregnancy may have adverse effects on social play behavior across two generations of offspring.

Transgenerational neurotoxic effects of triphenyltin on marine medaka: Impaired dopaminergic system function

Triphenyltin (TPT), a widely used environmental contaminant in antifouling paints, is known for its neurotoxic effects. To investigate the multigenerational impacts of long-term exposure (6 weeks) to environmental concentrations of TPT (100 ng/L) on either parent, we performed mixed mating between control and exposed groups (males or females). Although there was no direct contact with TPT in the subsequent generations, both the first and second generations displayed behavioral abnormalities, including reduced activity and impaired cognitive function, with pronounced gender differences and anxiety-like behaviors. Females were more susceptible than males, displaying a significantly increased time spent in the mirror-proximal zone in both F1 and F2 generations. Additionally, F0 females exhibited a marked reduction in the time spent in the bright area, further supporting the role of sex differences in behavioral responses. Notably, the maternal contribution of marine medaka (Oryzias melastigma) played a more significant role in the inheritance of TPT-induced cognitive deficits. A reduction in DA levels and AChE activity was observed across generations, regardless of gender, underscoring the critical role of DA-AChE balance in maintaining cognitive function. Additionally, gender differences and the hereditary effects of TPT exposure on anxiety-like behaviors were strongly associated with the transcriptional regulation of pparγ and gst. Impaired transcription of key genes in the dopaminergic system resulted in reduced DA levels, with the intergenerational transmission of mao being closely linked to behavioral impairments. In summary, TPT-induced neurotoxicity presents both hereditary effects and gender-specific differences, emphasizing the maternal influence in the inheritance of cognitive abilities and shedding light on the genetic impact of parental exposure.

Sex-specific neurotoxicity and transgenerational effects of an emerging pollutant, tris(1,3-dichloro-2-propyl)phosphate (TDCIPP)

The growing production and usage of flame retardants (FRs) results in their extensive environmental distribution, potentially posing a threat on both ecological and human health. Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP), a commonly used FR, is commonly found in aquatic ecosystems, and aquatic organisms, including fish, may be exposed to TDCIPP during specific stages of their life cycles, or across generations. Here, we aim to identify and compare the neurotoxic effects of TDCIPP on the brains of female and male adult marine medaka (Oryzias melastigma) across three generations (F0 to F3). Sex-specific effects of TDCIPP related to synaptic transmission signaling pathways and regulation of neuronal synaptic plasticity underlying 1917 differentially expressed genes (DEGs) were evident in the brain transcriptomes of F0 females, while only five DEGs were found in F0 males. However, chronic exposure over three generations (F0 to F3) revealed neurotoxic effects of TDCIPP on both sexes with males altering their innate immune response and visual perception upon prolonged exposure. Lastly, female medaka exhibited signals of transgenerational effects at the F3, as shown by increased transcriptional adjustments of 2347 DEGs including epigenetic regulatory genes. This outcome resulted from the ancestral exposure to TDCIPP only in F0, without any direct TDCIPP exposure in F1 and F2. Our findings show that even brief exposure to TDCIPP result in long-lasting effects, posing a significant risk to marine organisms and potentially other vertebrates.

Biological performance of Bollgard II® Bt-resistant vs susceptible population of pink bollworm, Pectinophora gossypiella (Saunders) on non-toxic diet

BackgroundThe pink bollworm, Pectinophora gossypiella (Saunders), is a devastating global pest of cotton that has caused substantial economic damage to Bt Bollgard-II® cotton plants in recent years due to the evolution of Bt resistance. The associated fitness cost is assumed to be one of the factors delaying the development of resistance against Bt transgenic crops. Hence, the present study was undertaken to assess the biological performance of pink bollworms by comparing the life history and demographic parameters of a resistant (Field-R) and susceptible (Lab-S) population.ResultsProlonged larval duration (23.40 days in Field-R vs 18.80 days in Lab-S population), total life cycle (male = 50.00 vs 42.80 days; female = 53.60 vs 46.20 days), reduced fecundity (100.60 vs 154.20 eggs/female) and fertility (88.00 vs 138.00 fertile eggs/female) was observed. The demographic parameters indicated a significant reduction in the net reproductive rate (184.27 vs 276.72), innate capacity for increase in number (0.11 vs 0.15), finite rate of increase in number (1.12 vs 1.16 female progenies produced/female/day), weekly multiplication rate (2.16 vs 2.86), potential fecundity (545.06 vs 634.11 eggs), number of hypothetical F2 females (33 955.65 vs 76 572.41), but longer mean length of generation (47.54 vs 37.74 days) and population doubling time (6.30 vs 4.62 days) in Field-R compared with Lab-S population. A stage-specific life table demonstrated the differences in survival rates between susceptible and resistant populations at various life stages, with the resistant population having higher generation mortality (0.22 vs 0.19).ConclusionsThe study confirms the involvement of fitness costs associated with Bt resistance in P. gossypiella. Despite reduced reproductive fitness, the resistant population tried prolonging the larval stage as a compensatory mechanism to repair the damaged host tissues due to Bt intoxication and for accumulation of enough nutrient reserves for normal pupation and adult emergence. Presence of a high proportion of double Bt-resistant larvae in the field coupled with continued noncompliance with refug planting certainly favours the flaring up of this monophagous pest despite the observed fitness costs. The resistance cannot be effectively reversed unless suitable alternative management strategies are deployed.

Transgenerational Effects on Lifespan and Pathology of Paternal Pre-conceptional Exposure to Continuous Low-dose-rate Gamma Rays in C57BL/6J Mice.

The present work investigates the multigenerational effects of paternal pre-conceptional exposure to continuous low-dose-rate gamma rays in C56BL/6J mice. Male C57BL/6J (F0 sires) mice were exposed to low dose rates of 20, 1, and 0.05 mGy/day for 400 days, to total accumulated doses of 8,000, 400, and 20 mGy, respectively. Upon completion of the radiation exposure, the F0 male mice were immediately bred to non-irradiated 8-week-old C57BL/6J females (F0 dams) to produce the first-generation (F1) mice. Randomly selected F1 males and females were then bred to produce the second-generation (F2) mice. All the mice, except the F0 dams, were subjected to pathological examination upon natural death. Reproductive parameters, lifespan, causes of death, neoplasm incidences and non-neoplastic disease incidences were used as parameters to evaluate the biological effects of continuous pre-conceptional exposure of the sires (F0) to continuous low-dose-rate radiation. There were no significant differences in the pregnancy and weaning rates among the parent (F0) generation. Average litter size and average number of weaned pups (F1) from dams bred to males (F0) exposed to 20 mGy/day were significantly decreased compared to the non-irradiated controls. Significant lifespan shortening in the sires (F0) was observed only in the 20 mGy/day group due to early death from malignant lymphomas. Life shortening was also observed in the F1 progeny of sires (F0) exposed to 20 and 1 mGy/day, but could not be attributed to a specific cause. No significant differences in the causes of death were found between dose groups in any generation. The number of primary tumors per mouse was significantly increased only in the F0 males exposed to 20 mGy/day. Except for the increased incidence rate for Harderian gland neoplasms in sires (F0) exposed to 20 mGy/day, there was no significant difference in neoplasm incidences and tumor spectra in all 3 generations in each sex regardless of radiation exposure. No multi- or transgenerational effects in the parameters examined were observed in the F1 and F2 progeny of sires exposed to 0.05 mGy/day for 400 days.

Thyroid endocrine disruption effects of OBS in adult zebrafish and offspring after parental exposure at early life stage

As an alternative to perfluorooctane sulfonate, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been widely used and caused ubiquitous water pollution. However, its toxicity to aquatic organisms is still not well known. Therefore, in this study, parental zebrafish were exposed to OBS at environmentally relevant concentrations from ∼ 2 h post-fertilization to 21 days post-fertilization (dpf) in order to investigate the thyroid disrupting effects in F0 adults and F1 offspring. Histopathological changes, such as hyperplasia of thyroid follicular epithelia and colloidal depletion, were observed in F0 adults at 180 dpf. In F0 females, thyroxine (T4) levels were significantly reduced in 30 and 300 μg/L exposure groups, while triiodothyronine (T3) levels were significantly increased in 3 μg/L exposure group. For F0 males, significant increases of T4 and T3 levels were observed, revealing the sex-specific differences after the OBS exposure. The transcription levels of some key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were significantly disrupted, which induced the thyroid endocrine disruption effects in adult zebrafish even after a prolonged recovery period. For F1 offspring, the thyroid hormone (TH) homeostasis was also altered as T4 and T3 levels in embryos/larvae exhibited similar changes as F0 females. The transcription levels of some key genes related to the HPT axis were also significantly dysregulated, suggesting the transgenerational thyroid disrupting effects of OBS in F1 offspring. In addition, the decreased swirl-escape rate was observed in F1 larvae, which could be caused by disrupting gene expressions related to the central nervous system development and be associated with the TH dyshomeostasis. Therefore, parental OBS exposure at early life stage resulted in thyroid endocrine disruption effects in both F0 adult zebrafish and F1 offspring, and caused the developmental neurotoxicity in F1 larvae.

Sharp decline in male fertility in F2 hybrids of the female-heterogametic silk moth Bombyx.

Sexual selection drives rapid evolution of morphological, physiological, and behavioral traits, especially in males, and it may also drive the rapid evolution of hybrid male sterility. Indeed, the faster male theory of speciation was once viewed as a major cause of Haldane's rule in male-heterogametic XY taxa, but is increasingly being replaced by the genetic conflict hypothesis partly because it cannot explain the faster evolution of hybrid female sterility in female-heterogametic ZW taxa. The theory nonetheless predicts that there should be more genes for hybrid male sterility than for hybrid female sterility even in such taxa, but this remains untested. Thus, finding evidence for the faster male theory of reproductive isolation beyond the F1 generation in ZW systems still represents a challenge to studying the impact of sexual selection. In this study, we examined F2 hybrids between the domesticated silkworm Bombyx mori and the wild silk moth Bombyx mandarina, which have ZW sex determination. We found that although only females showed reduced fertility in the F1 generation, the F2 hybrid males had a significant reduction in fertility compared with the parental and F1 males. Importantly, 27% of the F2 males and 15% of the F2 females were completely sterile, suggesting the presence of recessive incompatibilities causing male sterility in female-heterogametic taxa.

Sublethal effects of emamectin benzoate on biological characteristics and the expression of vitellogenin (SgVg) and its receptor in Sclerodermusguani

Emamectin benzoate (EMB) is a commonly used insecticide for controlling agricultural and forest pests. To facilitate its rational use in integrated pest management (IPM), the sublethal effects of EMB on the development and reproduction of Scleroderma guani were evaluated. Sublethal doses of EMB (LD10 and LD30) significantly reduced the longevity and fecundity of F0 females. In the F1 generation, sublethal doses significantly reduced larval development duration and male longevity but significantly extended female longevity. Additionally, the LD30 treatment significantly decreased the number of laid eggs in F1 females by 20.72% compared with the control group. The net reproductive rate (R0) was significantly declined by the LD30 treatment compared with the control group (CK). Furthermore, the mean generation time (T) was significantly extended in both LD10 and LD30 treatment groups. Compared to the control group, the expression of SgVg and SgVgR genes in the LD10 and LD30 groups was significantly lower, which may be a crucial factor for the reduced fecundity of the females. These results indicate that sublethal doses of EMB significantly reduced adult longevity and fecundity of S. guani. The findings are practical for developing IPM strategies for forestry pests using S. guani and EMB.

Maternal high-fat high-sugar diet impairs bone quality and strength but not cartilage in aging mice.

Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high-fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high-fat high-sugar (HFHS) diet would promote spontaneous osteoarthritis-related cartilage and bone changes in 1-year-old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow-fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation. Male and female offspring were weaned onto a chow diet, raised to 1 year of age, and evaluated for cartilage and bone changes indicative of OA. However, offspring did not show early signs of OA as measured by histological Mankin scoring, mechanical testing of the pericellular matrix, histological synovitis scoring, or subchondral bone thickening as measured by microcomputed Tomography. On the other hand, male offspring from HFHS-fed dams had reduced trabecular bone quality in the tibial metaphysis and decreased cortical thickness. Although maternal HFHS diet did not impact trabecular or cortical bone quality in tibias of female offspring, the radii of these animals had decreased cortical thickness, increased medullary area, and impaired breaking strength compared to those of control-fed dams. Finally, we evaluated bone quality and strength in male and female F2 offspring and found that the grandmaternal diet modestly impacted radial bone geometry but not strength. Together these results suggest that maternal HFHS diet impairs F1 offspring skeletal integrity in a sex and bone site-specific manner.

Paternal preconception donepezil exposure enhances learning in offspring

BackgroundRecent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring.ResultsIn this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements.ConclusionsThese findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Depletion of the paternal gut microbiome alters sperm small RNAs and impacts offspring physiology and behavior in mice

The paternal environment prior to conception has been demonstrated to influence offspring physiology and behavior, with the sperm epigenome (including noncoding RNAs) proposed as a potential facilitator of non-genetic inheritance. Whilst the maternal gut microbiome has been established as an important influence on offspring development, the impact of the paternal gut microbiome on offspring development, health and behavior is largely unknown. Gut microbiota have major influences on immunity, and thus we hypothesized that they may be relevant to paternal immune activation (PIA) modulating epigenetic inheritance in mice. Therefore, male C57BL/6J mice (F0) were orally administered non-absorbable antibiotics via drinking water in order to substantially deplete their gut microbiome. Four weeks after administration of the antibiotics (gut microbiome depletion), F0 male mice were then mated with naïve female mice. The F1 offspring of the microbiome-depleted males had reduced body weight as well as altered gut morphology (shortened colon length). F1 females showed significant alterations in affective behaviors, including measures of anxiety and depressive-like behaviors, indicating altered development. Analysis of small noncoding RNAs in the sperm of F0 mice revealed that gut microbiome depletion is associated with differential expression of 8 different PIWI-interacting RNAs (piRNAs), each of which has the potential to modulate the expression of multiple downstream gene targets, and thus influence epigenetic inheritance and offspring development. This study demonstrates that the gut-germline axis influences sperm small RNA profiles and offspring physiology, with specific impacts on offspring affective and/or coping behaviors. These findings may have broader implications for other animal species with comparable gut microbiota, intergenerational epigenetics and developmental biology, including humans.

Epigenetic alteration of uterine Leukemia Inhibitory Factor gene after glyphosate or a glyphosate-based herbicide exposure in rats

Glyphosate-based herbicides (GBHs) or its active ingredient, glyphosate (Gly), induce implantation failure in rats. We aimed to elucidate a mechanism of action of these compounds assessing the transcriptional and epigenetic status of the receptivity marker, leukemia inhibitory factor (Lif) gene. F0 rats were orally exposed to GBH or Gly at 3.8 or 3.9 mg Gly/kg/day, respectively, from gestational day (GD) 9 until weaning. F1 females were mated and uterine samples collected at GD5. Methylation-sensitive restriction enzymes (MSRE) sites and transcription factors were in silico predicted in regulatory regions of Lif gene. DNA methylation status and histone modifications (histone 3 and 4 acetylation (H3Ac and H4Ac) and H3 lysine-27-trimethylation (H3K27me3)) were assessed. GBH and Gly decreased Lif mRNA levels and caused DNA hypermethylation. GBH increased H3Ac levels, whereas Gly reduced them; both compounds enhanced H3K27me3 levels. Finally, both GBH and Gly induced similar epigenetic alterations in the regulatory regions of Lif.

Paternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring.

Emerging studies suggest that various parental exposures affect offspring cardiovascular health, yet the specific mechanisms, particularly the influence of paternal cardiovascular disease (CVD) risk factors on offspring cardiovascular health, remain elusive. The present study explores how paternal hypercholesterolemia affects offspring atherosclerosis development using the LDL receptor-deficient (LDLR-/-) mouse model. We found that paternal high-cholesterol diet feeding led to significantly increased atherosclerosis in F1 female, but not male, LDLR-/- offspring. Transcriptomic analysis highlighted that paternal hypercholesterolemia stimulated proatherogenic genes, including Ccn1 and Ccn2, in the intima of female offspring. Sperm small noncoding RNAs (sncRNAs), particularly transfer RNA-derived (tRNA-derived) small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), contribute to the intergenerational transmission of paternally acquired metabolic phenotypes. Using a newly developed PANDORA-Seq method, we identified that high-cholesterol feeding elicited changes in sperm tsRNA/rsRNA profiles that were undetectable by traditional RNA-Seq, and these altered sperm sncRNAs were potentially key factors mediating paternal hypercholesterolemia-elicited atherogenesis in offspring. Interestingly, high-cholesterol feeding altered sncRNA biogenesis-related gene expression in the epididymis but not testis of LDLR-/- sires; this may have led to the modified sperm sncRNA landscape. Our results underscore the sex-specific intergenerational effect of paternal hypercholesterolemia on offspring cardiovascular health and contribute to the understanding of chronic disease etiology originating from parental exposures.

Perinatal Exposure to Glyphosate or a Commercial Formulation Alters Uterine Mechanistic Pathways Associated with Implantation Failure in Rats.

Perinatal exposure to a glyphosate-based herbicide (GBH) or its active ingredient, glyphosate (Gly), has been demonstrated to increase implantation failure in rats. This study investigates potential mechanisms of action, analyzing uterine preparation towards the receptive state. Pregnant Wistar rats (F0) were treated orally with GBH or Gly (3.8 and 3.9 mg Gly/kg/day, respectively) from gestational day (GD) 9 until weaning. Adult F1 females became pregnant and uterine samples were collected on GD5 (preimplantation period). Histomorphological uterine parameters were assessed. Immunohistochemistry was applied to evaluate cell proliferation and protein expression of estrogen receptors (ERα and ERβ), cell cycle regulators (PTEN, cyclin G1, p27, and IGF1R-α), and the Wnt5a/β-catenin/FOXA2/Lif pathway. Both GBH and Gly females showed increased stromal proliferation, associated with a high expression of ERs. Dysregulation of PTEN and cyclin G1 was also observed in the Gly group. Reduced gland number was observed in both groups, along with decreased expression of Wnt5a/β-catenin/FOXA2/Lif pathway in the glandular epithelium. Overall, GBH and Gly perinatal exposure disrupted intrinsic uterine pathways involved in endometrial proliferation and glandular function, providing a plausible mechanism for glyphosate-induced implantation failure by compromising uterine receptivity. Similar effects between GBH and Gly suggest the active principle mainly drives the adverse outcomes.

Asymmetric mate preference and reproductive interference mediate climate-induced changes in mate availability in a small mammal hybrid zone.

Range expansion and contraction are among the most common biotic responses to changing environmental conditions, yet much is to be learned about the mechanisms that underlie range-edge population dynamics, especially when those areas are points of secondary contact between closely related species. Here, we present field-measured parentage data that document the reproductive outcomes of changes in mate availability at a secondary contact zone between two species of woodrat in the genus Neotoma. Changes in mate availability resulted from drought-driven differential survival between the species and their hybrids. As the availability of conspecific mates declined, rates of hybridization increased, leading to the accumulation of admixed individuals in the zone of contact. Patterns of reproductive success in the wild appear to be the result of a combination of both pre-mating isolation and post-zygotic selection resulting from genomic incompatibilities between the parental lineages. Evidence of asymmetric mate preference between the parental lineages came from both skewed reproductive output in the field and laboratory preference trials. Moreover, partial genomic incompatibility was evident from the near-zero reproductive success of F1 males and because nearly all surviving hybrids had one pure parent. Nonetheless, the high reproductive success of F1 females and backcrossing in both parental directions allow for introgression between the parental species. These findings reveal how climate change may alter evolutionary outcomes for species at the edge of their ranges through an interplay of behavioral, demographic, and genetic mechanisms.