Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Evaluation of two beef cow fixed-time AI protocols that utilize presynchronization.

Presynchronization was evaluated as a method to improve estrus response before fixed-time AI (FTAI). The objective was to compare FTAI results in beef cows from two different presynchronization approaches. Blood samples were collected on Day -14 (Day 0 = CIDR removal) to determine progesterone concentration (≥1 ng/mL = high, <1 ng/mL = low). In a subset (n = 1289), an additional blood sample was collected between Day -21 and -29 to determine cyclicity (if both the Day -14 and Day -21 to -29 samples were classified as low progesterone cows were classified as noncycling). Cows (n = 1388) from 30 herds were grouped by days postpartum (DPP) and age, and randomly assigned to either of two protocols. Cows assigned to the PG 6-day CIDR & FTAI protocol (PG6d) received prostaglandin F2α (PG) on Day -9, CIDR insertion and GnRH on Day -6, and CIDR removal and PG on Day 0. Cows assigned to the 7&7 Synch protocol (7&7) were administered PG and CIDR insertion on Day -14, GnRH on Day -7, and CIDR removal and PG on Day 0. For both protocols, FTAI occurred concurrently with GnRH 66 h after second PG. Pregnancy was determined by transrectal ultrasonography 30-40 d after FTAI. The GLIMMIX procedure of SAS was used to detect differences in estrus response and pregnancy success with herd as a random variable. Estrus response (0-66 h) was analyzed with two models, one included cyclicity and another replaced cyclicity with progesterone concentration at Day -14. In both models, cows assigned to the 7&7 protocol had greater (P < 0.01) estrus response than cows assigned to the PG6d protocol. The model including cyclicity, estrus response was impacted by the cyclicity by DPP interaction (P = 0.03), cyclicity by protocol interaction (P = 0.04), and the tendency of BCS by protocol interaction (P = 0.08). In the estrus response model that included progesterone concentration at Day -14, significant variables included the protocol by progesterone concentration at Day -14 (P = 0.01), and BCS (P < 0.01), while DPP (P = 0.08) and progesterone concentration at Day -14 (P = 0.07) were tendencies. Pregnancy success was influenced by estrual status (P < 0.01), body condition score (P = 0.04), and cycling status (P = 0.02), but was not influenced by protocol (P = 0.75; PG6d = 38 ± 5% and 7&7 = 37 ± 5%). In conclusion, effectiveness of presynchronization method depended on a cows' physiological status, and the 7&7 protocol increased estrus response compared with PG6d, but there was no difference in pregnancy success.

High glucose exposure of preimplantation embryos causes glucose intolerance and insulin resistance in F1 and F2 male offspring.

BACKGROUND: Although studies suggest that maternal high glucose (HG) increases offspring susceptibility to type 2 diabetes mellitus (T2DM), the underlying mechanisms are largely unclear. We studied whether glucose levels in oviducts are elevated when pregestational diabetic females get pregnant and whether the oviductal HG (OVHG) would act directly on embryos to increase offspring's T2DM susceptibility. METHODS: We established an in vivo model of OVHG by injecting female mice with streptozotocin (STZ) during the preimplantation period and an in vitro model of embryo culture with HG (ECHG) by culturing preimplantation embryos with HG, before examining glucose tolerance and insulin resistance (IR) in F1 and F2 offspring. FINDINGS: Injection of female mice with STZ induced a lasting significant glucose elevation in blood and oviduct fluid during the preimplantation period. The glucose tolerance test showed that both the STZ-induced OVHG and the ECHG caused glucose intolerance in F1 male and F1-sired F2 male offspring but had no effect on female offspring. Insulin tolerance test and the analysis for IR-related gene expression and glycogen contents in liver and muscle revealed significant IR in these male offspring. INTERPRETATION: This study provided evidence that HG can act directly on preimplantation embryos to increase offspring's T2DM susceptibility suggesting that the preimplantation period is a critical stage for transmission of mother's diabetes to offspring. FUND: This study was supported by grants from the China National Natural Science Foundation (Nos. 31772599, 32072738, 31702114, and 31902160), and the Natural Science Foundation of Shandong Province (Nos. ZR2022MC036, ZR2017BC025 and ZR2020QC102).

Neuroinflammation in fetal alcohol spectrum disorders and related novel therapeutic approaches.

Fetal alcohol spectrum disorders (FASD) is an umbrella term to describe the neurological effects of prenatal alcohol exposure (PAE). It has been extensively characterized that PAE causes cell proliferation disruption, heterotopias, and malformations in various brain regions and there is increasing evidence that neuroinflammation is responsible for some of these neurotoxic effects. Despite evidence of its importance, neuroinflammation is not usually considered at diagnosis or treatment for FASD. Here, we discuss the literature regarding anti- inflammatory drugs and nutraceuticals, which hold promise for future therapeutical interventions in these disorders.

Exploration of the mechanisms of improving learning and memory in the offspring of aging pregnant mice by supplementation with Paris polyphylla polysaccharide based on the P19-P53-P21 and Wnt/ß-catenin signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: First recorded in "Sheng Nong's herbal classic", Paris polyphylla is used to treat diseases, such as convulsions, head shaking and tongue fiddling, and epilepsy. Studies have shown that the ability of three Liliaceae polysaccharides in improving learning and memory may be related to the P19-P53-P21 and Wnt/ß-catenin signaling pathways. Moreover, a link between these two signaling pathways and the possible neuroprotective impact of Paris polyphylla polysaccharide has been proposed. AIM OF THE STUDY: We explored the mechanisms of improving learning and memory in the offspring of pre-pregnant parental mice and D-galactose-induced aging pregnant mice by supplementation with P. polyphylla polysaccharide based on the P19-P53-P21 and Wnt/ß-catenin signaling pathways. STUDY DESIGN AND METHODS: After 3 weeks of supplementation of D-galactose-induced pre-pregnant parental mice with P. polyphylla polysaccharide component 1 (PPPm-1), the male and female parental mice mated in cages. The D-galactose-induced pregnant mice were continued to be supplemented with PPPm-1 for 18 days before delivery of the offspring. Behavioral experiments (Morris water maze and dark avoidance experiments) were conducted on the offspring mice born 48 days later to determine whether PPPm-1 had the effect of improving their learning and memory. Based on the P19/P53/P21 and Wnt/ß-catenin signaling pathways, the mechanisms of PPPm-1 in improving learning and memory in offspring mice were further investigated. RESULTS: Offspring mice administered low- or high-dose PPPm-1 exhibited stronger motor and memory abilities in behavioral experiments than the aging model of offspring mice. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed that the expressions of P19 and P21 mRNA and protein were inhibited in offspring mice administered low- and high-dose PPPm-1. However, P53 expression was inhibited in the low-dose PPPm-1 offspring group but promoted in the high-dose PPPm-1 offspring group. Additionally, PPPm-1 could effectively activate the Wnt/ß-catenin signaling pathway, promote the expressions of Wnt/1, ß-catenin, CyclinD1, and TCF-4 mRNA and protein, and inhibit GSK-3ß mRNA and protein expression to improve the learning and memory abilities of offspring mice. CONCLUSION: Thus, PPPm-1 improved the learning and memory abilities in the offspring of aging pregnant mice by acting on the P19-P53-P21 and Wnt/ß-catenin signaling pathways.

Bushen Antai recipe ameliorates immune microenvironment and maternal-fetal vascularization in STAT3-deficient abortion-prone mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Spontaneous abortion (SA) is an intricate disorder affecting women of reproductive age. Previous studies have confirmed the indispensable role of signal transducer and activator of transcription (STAT) 3 in normal pregnancy. Bushen Antai recipe (BAR) is a satisfactory formula commonly used in practice, based on the rationale of traditional Chinese medicine (TCM) for SA. AIM OF THE STUDY: The current study explores the potential therapeutic effects and mechanistic insights of BAR in STAT3-deficient abortion-prone mice. MATERIALS AND METHODS: A STAT3-deficient abortion-prone mouse model was developed using intraperitoneal injection of stattic from embryo day (ED) 5.5 to ED9.5 among pregnant females (C57BL/6). We separately administered BAR1 (5.7 g/kg), BAR2 (11.4 g/kg), progesterone (P4), or distilled water at 10 ml/kg/day from ED0.5 until ED10.5. The embryo resorption rate and placenta-uterus structure were observed on ED10.5. The systemic immune status was examined by analyzing the frequency of immunosuppressive myeloid-derived suppressor cells (MDSCs), the ratio of two macrophage (M) subtypes, and the protein expression of associated molecules. Morphological observation, immunohistochemistry, and western blotting were used to evaluate the vascularization conditions at the maternal-fetal interface. RESULTS: BAR1, BAR2, or P4 treatment exerted remarkable effects in alleviating embryo resorption rate and disordered placental-uterus structure in STAT3-deficient abortion-prone mice. Western blotting indicated the deficiency of phosphorylated STAT3 and two prime target molecules, PR and HIF-1α, at the maternal-fetal interface under STAT3 inhibition. Simultaneously, BAR2 treatment significantly upregulated their expression levels. The systemic immune environment was disrupted, indicated by the reduced serum cytokine concentrations, MDSCs frequency, M2/M1 ratio, and the expression of immunomodulatory factors. Nonetheless, BAR2 or P4 treatment revived the immune tolerance for semi-allogenic embryos by enhancing the immune cells and factors. Besides, the western blot and immunohistochemistry results revealed that BAR2 or P4 treatment upregulated VEGFA/FGF2 and activated ERK/AKT phosphorylation. Therefore, BAR2 or P4 facilitated vascularization at the maternal-fetal interface in STAT3-deficient abortion-prone mice. CONCLUSIONS: BAR sustained pregnancy by reviving the systemic immune environment and promoting angiogenesis at the maternal-fetal interface in STAT3-deficient abortion-prone mice.

Jiawei Shoutai Pill promotes decidualization by regulating the SGK1/ENaC pathway in recurrent spontaneous abortion.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Shoutai Pill (JWSTW) is a traditional herbal formula for recurrent spontaneous abortion (RSA). Although JWSTW significantly improves the clinical symptoms of RSA patients, its molecular mechanism remains unclear. AIM OF STUDY: This study evaluated the expression and function of the serum/glucocorticoid regulated kinase 1/epithelial sodium channel (SGK1/ENaC) pathway and decidualization level in RSA patients and mice. It also investigated the therapeutic effects and potential mechanisms of JWSTW. MATERIALS AND METHODS: 30 early RSA patients and 30 normal pregnant women undergoing induced abortion during the same period were included in the study. Decidual tissues were collected, and HE staining, immunohistochemistry, Western blot, and RT-PCR were used to detect protein and mRNA expression levels of SGK1, ENaC-a, estrogen Rreceptor ß (ERß), and progesterone receptor (PR) in patients' decidual tissues. Protein expression levels of prolactin receptor (PRLR) and insulin-like growth factor binding protein 1 (IGFBP-1) were also detected. A classical RSA mouse model was constructed, and the mice were randomly divided into four groups: normal, model, dydrogesterone (DQYT) (0.33 g/kg/d), and JWSTW (1.66 g/kg/d). The normal and model groups received the same volume of distilled water by gavage for 8 and 14 days after pregnancy. On the 14th day of pregnancy, the embryonic loss rate of each group, the number of offspring born to naturally delivered mice, and the protein or mRNA expression levels of key factors of the SGK1/ENaC pathway (SGK1, ENaC-a, ERß, and PR), decidual proliferation marker (Ki67), mesenchymal-epithelial transition (E-cadherin and Vimentin), and decidualization markers (PRLR and IGFBP-1) in mouse decidual tissue on the eighth day of pregnancy were observed. RESULTS: The decidual tissue structure of RSA patients was abnormal. Immunohistochemical analysis revealed significantly reduced positive expression of SGK1, ENaC-a, ERß, and PR proteins in the decidual tissue of RSA patients (P < 0.001). Western blot and RT-PCR analyses demonstrated significantly decreased protein and mRNA expression of SGK1, ENaC-a, ERß, and PR in the decidual tissue of RSA patients (all P < 0.05). Additionally, protein expression of PRLR and IGFBP-1 was significantly reduced (both P < 0.001). The RSA mouse model exhibited a significant increase in embryo loss rate and decreased litter size (both P < 0.001). Treatment with DQYT and JWSTW rescued the embryo loss rate and litter size to varying extents (all P < 0.05). The protein or mRNA expression levels of SGK1, ENaC-a, ERß, PR, Ki67, E-cadherin, vimentin, PRLR, and IGFBP-1 in RSA mice were improved to different degrees after treatment with DQYT and JWSTW (all P < 0.05). CONCLUSIONS: Abnormal SGK1/ENaC signaling pathway regulation is closely associated with early endometrial damage in RSA patients. JWSTW promotes endometrial proliferation and mesenchymal-epithelial transition through the SGK1/ENaC signaling pathway, improving endometrial shedding. Consequently, JWSTW is a potential treatment for RSA.

In view of ovarian steroidogenesis and luteal construction to explore the effects of Bushen Huoxue recipe in mice of ovarian hyperstimulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Huoxue recipe (BSHXR) is a widely used prescription medicine for treating gynecological diseases. We have previously found that BSHXR can improve the pregnancy outcome of controlled ovarian hyperstimulation (COH) mice by modulating the abnormal high level of progesterone. While the pharmacological mechanism of such therapeutic effect is not clear. AIM OF THE STUDY: We aimed to investigate the effects of BSHXR on the ovarian steroidogenesis and luteal function in mice undergoing COH. MATERIALS AND METHODS: A COH mouse model was established via an intraperitoneal injection of 0.4 IU/g pregnant mare serum gonadotropin (PMSG) and 1 IU/g human chorionic gonadotropin (HCG). The histological features of ovaries were observed using hematoxylin-eosin staining. The expression levels of FSHR, LHCGR, and key molecules in ovarian steroidogenesis, including CYP11A1, CYP17A1, CYP19A1, HSD3B1, and StAR, were examined via immunohistochemical staining, western blotting, and RT-qPCR. CD31, VEGFA, and FGF2 levels were assessed to evaluate ovarian vascularization. The protein and mRNA levels of ovarian ERK1/2, p-ERK1/2, MEK1/2, and p-MEK1/2 were also detected using western blotting, RT-qPCR, or immunofluorescence staining. RESULTS: COH mice had a significantly increased volume and weight of the ovary and number of corpora lutea. In particular, COH exhibited a long-term influence on ovarian FSHR and LHCGR expression, disrupting the levels of CYP11A1, HSD3B1, and CYP17A1, causing poorer luteal angiogenesis. Compared with normal mice, the expression levels of ovarian VEGFA and FGF2 in COH mice were considerably lower on Day 1 after PMSG. On concomitant HCG treatment, both VEGFA and FGF2 expression surged dramatically on ED1 and then declined on ED4 and ED8. Moreover, the expression pattern of MEK1/2-ERK1/2 was almost consistent with that of VEGFA and FGF2. After treatment, BSHXR increased ovarian LHCGR, FSHR, CYP11A1, HSD3B1, and CYP17A1 levels, boosted luteal vascularization, and restored MEK1/2-ERK1/2 signaling in COH mice. CONCLUSION: BSHXR restored the abnormally high progesterone level by regulating the CYP11A1 and HSD3B1 expression as well as promoted luteal angiogenesis, which was related with LHCGR-MEK1/2-ERK1/2-VEGFA/FGF2 signaling pathway in the ovary. This effect prevented the fluctuation of sex hormones in COH mice and benefited the outcome of pregnancy.

Leptin decreases the transcription of BKCa channels and Gs to Gi protein-ratio in late pregnant rat uterus.

Obesity can have a significant impact on pregnancy outcomes by compromising the ability of the uterus to relax, which increases the likelihood of conditions such as preterm labor. One of the key pathways responsible for uterine relaxation is the ß-adrenergic signaling pathway, and it is well-documented that obesity, often linked to a high-fat diet, can disrupt this pathway within the uterine environment. Hyperleptinemia is a significant feature of pregnancy as well as obesity. However, the effect of leptin on ß-adrenergic signaling pathway has not been studied. In the present study, we studied the effects of leptin on transcriptions of the major proteins defining the ß-adrenergic signaling pathway in pregnant rat uterus. Leptin treatment at a supraphysiological concentration to pregnant rat uterine strips increased the mRNA and protein expressions of Gs protein but not the mRNA of ß2- and ß3-adrenoceptors. It also enhanced the expression of Gi-protein, but not the Gq protein. Nevertheless, the mRNA ratio of Gs to Gi protein experienced a significant decrease. Further, leptin reduced the transcription of BKCaα and BKCaß channel subunits. In leptin-stimulated tissues, there was also an increase in the expression of leptin receptor and JAK-2. In conclusion, leptin decreases the ratio of Gs to Gi proteins and BKCaα and BKCaß channel subunits suggesting hyperleptinemia is a likely factor inducing uterine relaxant dysfunction in obesity.

Bell Palsy: Facts and Current Research Perspectives.

Bell palsy is a non-progressive neurological condition characterized by the acute onset of ipsilateral seventh cranial nerve paralysis. People who suffer from this type of facial paralysis develop a droop on one side of their face, or sometimes both. This condition is distinguished by a sudden onset of facial paralysis accompanied by clinical features such as mild fever, postauricular pain, dysgeusia, hyperacusis, facial changes, and drooling or dry eyes. Epidemiological evidence suggests that 15 to 23 people per 100,000 are affected each year, with a recurrence rate of 12%. It could be caused by ischaemic compression of the seventh cranial nerve, which could be caused by viral inflammation. Pregnant women, people with diabetes, and people with respiratory infections are more likely to have facial paralysis than the general population. Immune, viral, and ischemic pathways are all thought to play a role in the development of Bell paralysis, but the exact cause is unknown. However, there is evidence that Bell's hereditary proclivity to cause paralysis is a public health issue that has a greater impact on patients and their families. Delay or untreated Bell paralysis may contribute to an increased risk of facial impairment, as well as a negative impact on the patient's quality of life. For management, antiviral agents such as acyclovir and valacyclovir, and steroid treatment are recommended. Thus, early diagnosis accompanied by treatment of the uncertain etiology of the disorder is crucial. This paper reviews mechanistic approaches, and emerging medical perspectives on recent developments that encounter Bell palsy disorder.

Association of adverse fetal outcomes with placental inflammation after oral gestational exposure to hexafluoropropylene oxide dimer acid (GenX) in Sprague-Dawley rats.

Hexafluoropropylene oxide dimer acid (HFPO-DA), known as "GenX" for its trade name, is gradually taking the place of Perfluorooctanoic acid (PFOA). However, there is a poor understanding of the developmental effects of GenX. This study aims to explore whether GenX produces adverse effects on offspring development in Sprague-Dawley (SD) rats and the underlying mechanisms. Pregnant rats were orally administered with GenX (0, 1, 10 and 100 mg/kg/day) from gestational 0.5-19.5 days. Experimental data showed that the exposure to GenX resulted in increased rats' gestational weight gain, whereas both body weight and body length of their fetuses born naturally were significantly reduced. This could contribute to the developmental delays of fetal body weight, body length and tail length from postnatal 1-21 days. Histopathological evaluation of placenta indicated that GenX exposure led to neutrophil infiltration in decidual zone and congestion in labyrinth zone. Moreover, placental proteomics showed changes at the expression levels of the inflammation-related proteins in the Rap1 signaling pathway. In conclusion, gestational exposure to GenX induced fetal intrauterine and extrauterine development retardation in SD rats. Placental inflammation may play a key role in this process through the Rap1 signaling pathway.

The adverse impact of maternal ozone exposure on fetal growth in utero and the interaction with residential greenness.

This study aimed to investigate the effect of maternal ozone exposure on fetal growth during pregnancy, as well as the combined effect and interaction of ozone and residential greenness. We included a total of 14990 singleton pregnancies from the Fujian Birth Cohort Study. During pregnancy, fetal growth parameters including estimated fetal weight (EFW), femur length (FL), head circumference (HC), and abdominal circumference (AC). To investigate the associations between ozone exposure and the above-mentioned outcomes, generalized estimating equation approach and generalized linear regression were used, as appropriate. In the adjusted models, we observed that the Z scores of EFW (-0.031 (-0.048, -0.014)), FL (-0.021 (-0.038, -0.004)), and AC (-0.025 (-0.042, -0.007)) decreased with per interquartile range (IQR) increase of ozone concentration. Compared to participants with low ozone exposure and high NDVI, those with high ozone exposure and low NDVI experienced the largest decrease in Z scores for EFW (-0.049 (-0.079, -0.02)), FL (-0.034 (-0.063, -0.004)), HC (-0.034 (-0.065, -0.004)), and AC (-0.041 (-0.072, -0.01)), respectively. Interestingly, we discovered the effect modification of NDVI on the relationship between ozone exposure and fetal growth restriction (P for interaction < 0.05). This study established a negative relationship of maternal ozone exposure and fetal growth. Of importance, this study discovered the joint effect and interaction between ozone and residential greenness exposure.

Trophoblast organoids with physiological polarity model placental structure and function.

Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology and pathology. However, standard culturing of TOs does not recapitulate the cellular orientation of chorionic villi in vivo given that the multi-nucleated syncytiotrophoblast (STB) develops largely within the inner facing surfaces of these organoids (STBin). Here, we developed a method to culture TOs under conditions that recapitulate the cellular orientation of chorionic villi in vivo. We show that culturing STBin TOs in suspension with gentle agitation leads to the development of TOs containing the STB on the outer surface (STBout). Using membrane capacitance measurements, we determined that the outermost surface of STBout organoids contain large syncytia comprising >50 nuclei, whereas STBin organoids contain small syncytia (<10 nuclei) and mononuclear cells. The growth of TOs under conditions that mimic the cellular orientation of chorionic villi in vivo thus allows for the study of a variety of aspects of placental biology under physiological conditions.

Perinatal environmental enrichment changes anxiety-like behaviours in mice and produces similar intergenerational benefits in offspring.

Environmental enrichment implemented in early life is able to induce long-term changes in gene expression, synaptic function and behavioural responses. In this study, we evaluated the adult behavioural effects of perinatal environment enrichment in male and female mice (PEE), as well as the males and females of PEE male offspring (OPEE). For this purpose, animals were submitted to the following battery of behavioural analyses: elevated plus maze, open field test, light-dark box and novelty suppression feeding test. The frontal cortex and ventral hippocampus of PEE mice were collected for the evaluation of the expression of gamma-aminobutyric acid (GABA)-related genes. The PEE animals showed an increase in exploratory activity, associated with a reduction in anxiety-like behaviours on the elevated plus maze; this effect was mainly observed in males. Additionally, the male OPEE showed a reduction in anxiety-like behaviours on the elevated plus maze, mainly observed in a reduction of risk assessment-related behaviours. The PEE male mice also showed reduced expression of Gabra3 in the ventral hippocampus when compared to the control group. These results demonstrate that perinatal environmental enrichment promotes a reduction in anxiety-like behaviour that can be transferred intergenerationally.

Oxidative stress in donor mares for ovum pick-up delays embryonic development.

The in vitro production of equine embryos via ovum pick-up (OPU) and intracytoplasmic sperm injection (ICSI) has increased rapidly. There is a marked effect of the individual mare on the outcome of OPU-ICSI, but little is known about the influence of the mare's health condition. This study aimed to investigate the potential associations between the concentrations of interleukin-6 (IL-6), reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) in serum of oocytes' donor mares and the subsequent embryonic development. Just before OPU, a blood sample was collected from 28 Warmblood donor mares, that were subjected to a routine OPU-ICSI program. The serum concentrations of IL-6, d-ROMs, and BAP were assayed photometrically. The maturation, cleavage and blastocyst rate as well as the kinetics of blastocyst development were recorded. The average blastocyst rate was 24.68 ± 5.16% and the average concentrations of IL-6, d-ROMs, and BAP were 519.59 ± 157.08 pg/mL, 171.30 ± 4.55 carratelli units (UCARR), and 2711.30 ± 4.55 µmol/L, respectively. Serum concentrations of IL-6, d-ROMs, and BAP were not significantly different between mares yielding at least one blastocyst (552.68 ± 235.18 pg/mL, 168.36 ± 5.56 UCARR, and 2524.80 ± 159.55 µmol/L) and mares yielding no blastocysts (468.47 ± 179.99 pg/mL, 175.85 ± 7.89 UCARR, and 2999.50 ± 300.13 µmol/L, respectively). Serum concentrations of d-ROMs were significantly lower in mares with fast growing (at day 7-8 post ICSI; 148.10 ± 8.13 UCARR) compared to those with slow growing blastocysts (≥ day 9 post ICSI; 179.41 ± 4.89 UCARR; P = 0.003). Taken together, the serum concentration of IL-6, d-ROMs, and BAP do not determine the mare's ability to produce blastocysts in vitro. Although it may be questioned whether a single sample is representative of the mare's health status, changes in serum metabolites related to oxidative stress at the time of oocyte retrieval were linked to a delayed blastocyst development in a clinical OPU-ICSI outcome.

Maternal anxiety during pregnancy predicts infant attention to affective faces.

BACKGROUND: Prenatal maternal anxiety is a known influence on offspring development. General anxiety and pregnancy-related anxiety (a distinct type of anxiety encompassing fears associated with pregnancy) are associated with offspring socioemotional development, with potential consequences for later emotional and behavioral problems. This study examines whether maternal pregnancy-related and general anxiety relate to infant attention to affective faces, a process which plays an integral role in early socioemotional development. METHODS: Participants included 86 mothers and their 6-month-old infants (56.3 % female). Mothers completed measures of pregnancy-related and general anxiety three times through gestation. Infants' attention to affective faces was assessed with an eye-tracking task during which a series of face pairs were presented (happy, angry, or sad face paired with a neutral face). Overall attention measures included attention-holding (total looking time) and attention-orienting (latency to faces); affect-biased attention measures included proportion of total looking time to emotional faces and latency difference score. RESULTS: Higher maternal pregnancy-related anxiety across gestation predicted decreased infant attention-holding to affective faces [F(1,80) = 7.232, p = .009, partial η2 = 0.083]. No differences were found in infant attention-orienting or affect-biased attention. LIMITATIONS: Reliance on a correlational study design precludes the ability to make causal inferences. CONCLUSIONS: Maternal pregnancy-related anxiety is an important predictor of child outcomes. We provide novel evidence that pregnancy-related anxiety predicts infant attention to emotional faces, behaviors which have important implications for socioemotional development. Providers may consider pregnancy-related anxiety as a target for screening and treatment that may benefit both pregnant individual and offspring.

Childhood maltreatment, trait resilience and prenatal distress among expecting mothers and fathers in the FinnBrain Birth Cohort Study.

BACKGROUND: In this study we examined the association between childhood maltreatment exposure (CME) and psychological distress, including symptoms of depression and anxiety, during pregnancy. Additionally, we explored the potential moderating effect of trait resilience on these associations. METHODS: The study is part of the ongoing FinnBrain Birth Cohort Study. The sample consisted of 3016 mothers and 1934 fathers. The data were collected using self-report questionnaires, including EPDS, SCL-90, CD-RISC-10 and TADS. We conducted ANOVAs and linear logistic regression analyses to examine the associations between depression, anxiety, resilience, and CMEs. RESULTS: CMEs were associated with increased psychological distress, including depression symptoms and anxiety, and decreased trait resilience among both mothers and fathers. Additionally, trait resilience had a moderating effect on the association between fathers' CMEs and psychological distress, while no significant moderating effect was found among mothers. Furthermore, among both mothers and fathers, higher trait resilience was associated with decreased anxiety and depressive symptoms. LIMITATIONS: Due to cross-sectionality, it is not possible to establish a causal relationship between CMEs, resilience, and parental distress. Additionally, the study does not provide insights into the underlying factors or processes that contribute to the development of trait resilience. CONCLUSIONS: Trait resilience may have a positive impact on parents' mental health during pregnancy. This study is the first to investigate the significance of fathers' trait resilience during pregnancy. In clinical settings, it is essential to identify parents with low levels of resilience and provide them with appropriate support, recognizing them as a vulnerable group.

Exposure-based cognitive-behaviour therapy for anxiety-related disorders in pregnancy (ADEPT): Results of a feasibility randomised controlled trial of time-intensive versus weekly CBT.

BACKGROUND: Exposure-based cognitive-behaviour therapies (CBT) are effective but their acceptability in pregnancy is untested. Time-intensive delivery of CBT (INT-CBT) may accelerate treatment response. This feasibility trial aimed to explore this. METHODS: This multi-centre parallel-group trial recruited pregnant women with anxiety-related disorders via maternity and mental health settings and randomised (1:1) to INT-CBT (8-10 treatment hours over two weeks) or standard weekly one-hour CBT sessions (WCBT). Both groups also received late pregnancy and postpartum follow-ups. Participants received 10-12 total hours of individual therapy using remote delivery (95 %). Outcomes were assessed: at baseline; after two weeks of treatment, late pregnancy, at 1 and 3 months postpartum (by blinded assessors), alongside a qualitative interview. Pre-specified primary feasibility outcomes regarding acceptability, recruitment and retention were evaluated. The secondary outcome of adjusted mean difference was estimated for the proposed primary outcome. RESULTS: All feasibility outcomes were met. Of 135 screened, 59 women were randomised into the trial (29 INT-CBT:30 WCBT). 93 % completed treatment and 81 % provided data at 3 m postpartum. No adverse effects were attributable to treatment. Women receiving INT-CBT showed a reduction in anxiety (GAD-7) after two weeks of treatment compared to WCBT (aMD = -4.17, 95%CI -6.03 to -2.31) with narrower difference at 3-month postpartum aMD = -0.11 (95%CI -3.23, 3.00). Women described the momentum of INT-CBT as helpful to drive change. CONCLUSIONS: Exposure-based therapies are acceptable to pregnant women. INT-CBT may reduce anxiety quickly and should be tested in a confirmatory trial examining longer term outcomes. There may be limitations to generalisability from sampling and COVID. TRIAL REGISTRATION: doi:https://doi.org/10.1186/ISRCTN81203286 prospectively registered 27/6/2019.

Uterine secretome: What do the proteins say about maternal-fetal communication in buffaloes?

The aim was to compare the UF proteomics of pregnant and non-pregnant buffalo during early pregnancy. Forty-four females were submitted to hormonal estrus synchronization and randomly divided into two groups: pregnant (n = 30) and non-pregnant (n = 14). The pregnant group was artificially inseminated and divided into a further two groups: P12 (n = 15) and P18 (n = 15). Conceptus and uterine fluid samples were collected during slaughter at, respectively, 12 and 18 days after insemination. Of all the inseminated females, only eight animals in each group were pregnant, which reduced the sample of the groups to P12 (n = 8) and P18 (n = 8). The non-pregnant group was also re-divided into two groups at the end of synchronization: NP12 (n = 7) and NP18 (n = 7). The UF samples were processed for proteomic analysis. The results were submitted to multivariate and univariate analysis. A total of 1068 proteins were found in the uterine fluid in both groups. Our results describe proteins involved in the conceptus elongation and maternal recognition of pregnancy, and their action was associated with cell growth, endometrial remodeling, and modulation of immune and antioxidant protection, mechanisms necessary for embryonic maintenance in the uterine environment. SIGNIFICANCE: Uterine fluid is a substance synthesized and secreted by the endometrium that plays essential roles during pregnancy in ruminants, contributing significantly to embryonic development. Understanding the functions that the proteins present in the UF perform during early pregnancy, a period marked by embryonic implantation, and maternal recognition of pregnancy is of fundamental importance to understanding the mechanisms necessary for the maintenance of pregnancy. The present study characterized and compared the UF proteome at the beginning of pregnancy in pregnant and non-pregnant buffaloes to correlate the functions of the proteins and the stage of development of the conceptus and unravel their processes in maternal recognition of pregnancy. The proteins found were involved in cell growth and endometrial remodeling, in addition to acting in the immunological protection of the conceptus and performing antioxidant actions necessary for establishing a pregnancy.

Proteomics approach reveals urinary markers for early pregnancy diagnosis in buffaloes.

This study aimed to compare urine proteomics from non- and pregnant buffaloes in order to identify potential biomarkers of early pregnancy. Forty-four females underwent hormonal ovulation synchronization and were randomly divided into two experimental groups: inseminated (n = 30) and non-inseminated (n = 14). The pregnant females were further divided into two groups: pregnant at Day 12 (P12; n = 8) and at Day 18 (P18; n = 8) post-ovulation. The non-pregnant group was also subdivided into two groups: non-pregnant at Day 12 (NP12; n = 7) and at Day 18 (NP18; n = 7). Urine was collected from all females on Days 12 or 18. The samples were processed for proteomics. A total of 798 proteins were reported in the urine considering all groups. The differential proteins play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that some proteins from our study can be considered biomarkers for early pregnancy diagnosis, since they were increased in pregnant buffaloes. SIGNIFICANCE: Macromolecules have been studied for early pregnancy diagnosis, aiming to increase reproductive efficiency in cattle and buffaloes. Direct methods such as rectal palpation and ultrasonography have been considered late. Thus, this study aimed to compare urine proteomics from non- and pregnant buffaloes to identify potential biomarkers of early pregnancy. The differential proteins found in our study play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that these proteins can be considered possible biomarkers for early pregnancy diagnosis since they were increased in the pregnant buffaloes.