Male Fetuses Research Articles

Intrauterine fetal growth restriction in sheep leads to sexually dimorphic programming of Preadipocytes' differentiation potential.

Fetal growth restriction (FGR) is a risk factor for obesity in adult life. Importantly, growth-restricted females are more prone to obesity than males. The mechanisms involved in this sexually dimorphic programming are not known. Previously, we have demonstrated that ambient hyperthermia (40°C) led to placental insufficiency and significant FGR, and the perirenal adipose tissue undergoes sexually dimorphic gene expression. We demonstrated that males undergo significant changes in gene expression with growth restriction. This was not the case in females. We have also demonstrated that the isolated preadipocytes from male FGR (MFGR) have reduced differentiation potential compared to control males & females and female FGR (FFGR). Thus, we hypothesized that growth restriction differentially programs gene expression and genetic pathways in perirenal preadipocytes, which reduces their differentiation potential in male fetuses in a sexually dimorphic manner. We created FGR by exposing pregnant sheep to ambient hyperthermia. After isolating preadipocytes from perirenal adipose tissue, we differentiated them following published protocols. We examined the gene expression before and after differentiation from control male, control female, MFGR, and FFGR female. We also compared our data with other published studies in mouse and human preadipocytes. Our results demonstrate that a set of 21 genes altered with preadipocyte differentiation to mature adipocytes is common in adipose tissue from both sexes, humans, mice, and sheep, at different organismal ages (embryonic, fetal, and adult) and different sites (subcutaneous inguinal, pancreatic, perirenal). We also demonstrate that female FFGR fetuses demonstrate all these 21 genes altered similar to control males and females; however, MFGR fetuses have six genes (Dgat2, Fabp4, Lipe, Lrrfip1, Spred3, and Thrsp) that are not changed with preadipocyte differentiation to mature adipocyte. These genes may be responsible for reduced differentiation potential and obesity in FGR males compared to FGR females. Another important finding of the present study is that Lrrfip1, known to be associated with obesity, was upregulated with FGR and requires further investigation. Overall, our studies provide several target genes that may play a crucial role in reducing the risk of MFGR for obesity.

Thyroid FT4-to-TSH ratio in the first trimester is associated with gestational diabetes mellitus in women carrying male fetus: a prospective bi-center cohort study

Thyroid FT4-to-TSH ratio in the first trimester is associated with gestational diabetes mellitus in women carrying male fetus: a prospective bi-center cohort study

Urinary mycoestrogens and gestational weight gain in the UPSIDE pregnancy cohort

BackgroundZearalenone (ZEN), a secondary metabolite of Fusarium fungi, is one of the most common mycotoxins in global food supplies such as cereal grains and processed food. ZEN and its metabolites are commonly referred to as mycoestrogens, due to their ability to directly bind nuclear estrogen receptors α (ER-α) and β (ER-β). Zeranol, a synthetic mycoestrogen, is administered to U.S. cattle as a growth promoter. Despite widespread human exposure and ample evidence of adverse reproductive impacts in vitro and in vivo, there has been little epidemiological research on the health impacts of ZEN exposure during pregnancy. The objective of our study was to examine associations between ZEN and gestational weight gain (GWG).MethodsUrine samples were collected in each trimester from pregnant participants in the UPSIDE cohort (n = 286, Rochester, NY, USA). High performance liquid chromatography and high-resolution tandem mass spectrometry were used to quantify concentrations of ZEN as well as ∑mycoestrogens (composite sum of ZEN metabolites; ng/ml). Maternal weights at clinical visits were abstracted from medical records. We fitted longitudinal models of specific-gravity adjusted, log-transformed ZEN and ∑mycoestrogens in relation to total GWG (kilograms) and GWG rate (kilograms/week). We additionally examined risk of excessive GWG (in relation to Institute of Medicine guidelines) and considered effect modification by fetal sex.ResultsZEN and ∑mycoestrogens were detected in > 93% and > 95% of samples, respectively. Mycoestrogen concentrations were positively associated with total GWG (ZEN β:0.50 kg; 95%CI: 0.13, 0.87) and GWG rate (ZEN β:0.20 kg/week; 95%CI: 0.01, 0.03). Associations tended to be stronger among participants carrying male (versus female) fetuses and results were robust to adjustment for diet.ConclusionsMycoestrogen exposure during pregnancy may contribute to greater GWG. Future research is needed to understand potential influences on downstream maternal and offspring health.

Predicting Late-Term Pregnancy: The Role of Corrected Fetal Adrenal Gland Volume in Low-Risk Pregnants.

Late-term pregnancy is commonly seen in obstetrics and is linked to adverse outcomes. Corrected fetal adrenal gland volume (cAGV) is an ultrasound marker that was used to predict preterm labor. The objective was to determine whether cAGV, in conjunction with other maternal risk factors, could predict late-term pregnancy among low-risk pregnant women in order to improve obstetric care. A prospective study recruited 177 low-risk primigravida women. Ultrasound-based cAGV was calculated for all participants at 37 weeks. Participants were followed until the day of delivery; accordingly, they were divided into two groups: Control group (137/177) delivered at term (37 + 0/7-40 + 6/7) weeks and late-term group (40/177) who delivered at (41 + 0/7-41 + 6/7) weeks. Maternal age, body mass index (BMI), and gestational age were collected for all participants alongside ultrasound data such as fetal biometry, gender, and estimated fetal weight. The participants' mean age was (27.32 ± 5.17) years. The cAGV was significantly lower among pregnant women who passed their due dates and was inversely correlated to the gestational age (r = - 0.6, P < 0.001). The cAGV exhibited a high probability of predicting late-term pregnancy (OR = 3.47; 95% CI = 1.37 to 8.79; P = 0.009). In contrast, maternal age, maternal BMI, and the presence of a male fetus did not demonstrate any significance as predictors. The cAGV cut-off value (≤ 277mm3/kg) predicted late-term pregnancy (P < 0.001) at a 77.5% sensitivity and 91.2% specificity. The cAGV can predict late-term pregnancy with good sensitivity and specificity. It is proposed as a promising tool for clinical use as non-invasive ultrasound obtained at no extra cost during routine 2-dimensional ultrasound examinations. More studies are warranted to explore further applications in improving feto-maternal outcomes among late-term pregnnat.

Comparative study on pregnancy complications: PGT-A vs. IVF-ET with gender-specific outcomes.

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Sex-bias metabolism of fetal organs, and their relationship to the regulation of fetal brain-placental axis.

The placenta plays influential role in the fetal development of mammals. But how the metabolic need of the fetal organs is related to that of the placenta, and whether this relationship is influenced by the sex of the fetus remain poorly understood. This study used pigs to investigate metabolomic signatures of male and female fetal organs, and determine the relevance of gene expression of the placenta and brain to the metabolism of peripheral organs. Untargeted metabolomics analysis was performed with the day-45 placenta, kidney, heart, liver, lung and brain of male and female pig fetuses to model sex differences in themetabolism of the peripheral organs relative to that of the brain and placenta. Transcriptomic analysis was performed to investigate the expression of metabolic genes in the placenta and fetal brain of both sexes. The results of this study show that the fetoplacental metabolic regulation was not only influenced by the fetal sex but also dependent on the metabolic requirement of theindividual organs of the fetus. Neural network modeling of metabolomics data revealed differential relationship of the metabolic changes of the peripheral organs with the placenta and fetal brain between males and females. RNA sequencing further showed that genes associated with themetabolism of the peripheral organs were differentially expressed in the placenta and fetal brain. The findings of this study suggest a regulatory role of the fetal brain and placenta axis in the sex-bias metabolism of the peripheral organs.

Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection.

Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model. Using urine samples from a cohort of human pregnancies with or without UTI, we correlated urinary cytokines with birth outcomes and urine culture status. These analyses yielded a non-invasive, highly predictive three-model system for evaluating preterm birth risk implicating cytokines IL-10, IL-15, IL-1β, and IL-1RA. Our unique bimodal murine model coupled with patient samples provides a platform to investigate immunological and microbial factors governing UTI-associated preterm birth, revealing novel therapeutic opportunities to predict or prevent preterm birth.

A new spectrum of neonatal urethral pathologies in the era of early vesicoamniotic shunting?

Intrauterine vesicoamniotic shunting (VAS) was shown to affect survival of male fetuses with megacystis in suspected lower urinary tract obstruction (LUTO). Data on postnatal management are largely lacking. We aim to describe the pathologies diagnosed in children born after vesicoamniotic shunt placement in early pregnancy for megacystis. All newborns with previous intrauterine VAS treated in our institution were analyzed retrospectively. We evaluated the clinical spectrum of urethral pathologies. We also compared patients who received a shunt before the 17th gestational week with those who received it later. Between 2014 and 2023, 26 patients (all male) with a history of VAS for suspected LUTO were treated in our institution postnatally. Five fetuses with dislocated shunts underwent re-implantation in utero. Overall, premature birth before the 38th week of gestation was observed in 14 patients. Seven patients received a Harrison® shunt whereas 19 received a Somatex® shunt. Twelve patients required surgical shunt removal under general anesthesia due to shunt migration/embedding. Posterior urethral valves were found in 10/26 patients, 10/26 patients showed a urethral hypoplasia [Fig.1] and two patients had urethral duplications. In two patients, we identified a prune belly syndrome. One patient had posterior and anterior urethral valves. One patient had a high grade bilateral vesicoureteral reflux without LUTO. The 11 patients shunted early (before 17GW) showed a trend towards a higher proportion of urethral hypoplasia in the early shunt group (54% vs. 26%) without statistical significance. In our observation, patients treated with VAS had a noticeable high proportion of complex urethral pathologies such as urethral hypoplasia. These data should be taken into consideration for prenatal counselling of parents and planning of postnatal management.

Uterine Rupture Due to Oxytocin Overdose Leading to Dystocia in a Labrador Bitch

A three-year-old Labrador bitch brought to the TVCC-FVAS-BHU-Mirzapur, with the history of whelped one dead puppy 12 hrs before further no progress of delivery. The bitch administered with a total dose of 30 IU of oxytocin intramuscularly but there was no progress. Abdominal palpation revealed presence of fetal like mass and per-vaginal examination revealed presence of fetal parts in the birth canal. The bitch was treated with oxytocin @ 0.2 IU/kg body weight slow IV with 25% dextrose 0.2ml/kg body weight slow IV, a dead male fetus was removed through mutational operation after 15 minutes, after that no puppies were palpable. Radiographic examination revealed presence of four fetuses in the abdominal cavity. It was then decided to go for cesarean section. The surgical operation was done as per the standard routine procedures. The bitch was treated with antibiotic and analgesic for 3 days. The bitch had uneventful recovery with proper postoperative care. In the present study we concluded that the dystocia was due to uterine rupture and this can be corrected through exploratory laparotomy.

A fetus with a mass in the oral cavity: a rare case of large oral immature teratoma

Abstract Introduction/Objective Oral teratoma is a rare congenital neoplastic lesion composed of variable amounts of all three germ cell layers, comprising 2-9% of all teratomas. Teratomas are classified into subtypes depending upon the presence of immature components. Sacrococcygeal and head and neck regions are the most common sites, with slight female predominance. Mortality increases if diagnosed in the fetal or neonatal period. Methods/Case Report We report a case of male fetus diagnosed radiologically as ultrasound at 20 weeks of gestation revealed abnormal facial characteristics. A huge lump protruding from face measuring 10.8 x 6.7 cm was observed. Grossly a grey-white, multilobulated lesion was seen with cystic spaces originating from midline soft palate. Histologically an immature teratoma comprising bone, skin adnexae, glandular tissue and immature neuroepithelial tissue was identified. The case was distinguished as immature teratoma of the oropharynx. Results (if a Case Study enter NA) NA Conclusion Prenatal diagnosis with modalities including ultrasound, MRI, alpha fetoprotein concentrations, fetoscopy and fetal karyotyping is possible in early pregnancy which can aid in risk stratification and planning therapeutic interventions. Delayed diagnosis and treatment increase the likelihood of malignant transformation. Intrapartum intubation and resection of the tumor at the time of the cesarean section has shown better outcomes. However, despite all efforts, survival rates are low.

7441 KNDy Neurons and the Control of the Gonadotropic Axis in Midgestation Fetal Sheep

Abstract Disclosure: R. Amodei: None. S.S. Jonker: None. K. Gribbin: None. E. Lazen: None. C.T. Estill: None. C.E. Roselli: None. Recent evidence suggests that the neuropeptide kisspeptin (Kiss) plays a role to activate and regulate the male reproductive axis to secrete LH and testosterone during a time in gestation critical for brain sexual differentiation. KNDy neurons, an acronym for Kiss neurons that co-express neurokinin B (NKB) and dynorphin (Dyn), regulate pulsatile GnRH/LH secretion and are present in the hypothalamic arcuate nucleus of midgestation sheep fetuses. Notably, KNDy neurons are more abundant in female than in male fetuses. We hypothesize that KNDy-GnRH signaling is established during midgestation and that negative feedback mediated through KNDy neurons serves to regulate levels of testosterone needed for brain masculinization. In the current study, we used immunofluorescence histochemistry to assess the effect of testosterone manipulations on the number of arcuate Kiss neurons in male and female fetuses. In addition, we employed unanesthetized cannulated midgestation fetal sheep to test the effects of KNDy peptides on LH secretion and characterize receptor specificity in a real-time physiological context. We found that biweekly administration of testosterone propionate to the dam from Day 30–58 of gestation significantly increased (P &amp;lt; 0.05) plasma testosterone concentrations, which resulted in a significant decrease (P &amp;lt; 0.05) in both mean plasma LH concentrations and the number of arcuate Kiss neurons in female lamb fetuses. Conversely, chemical castration of midgestation male fetuses by treatment with the GnRH antagonist degarelix from day 60 – 90 of gestation resulted in a significant decrease (P &amp;lt; 0.05) in mean plasma LH and testosterone concentrations that was accompanied by a significant increase (P &amp;lt; 0.05) in the number of arcuate Kiss neurons. In unanesthetized fetuses, we found that bolus administration of both KP-10 (Kiss agonist) and senktide (NKB agonist) elicited a robust release of LH within 15 min. Treatment with the NK3 receptor antagonist SB222200 effectively blocked the senktide response, whereas the Kiss1 receptor antagonist P271 appeared to have an effect in males only. Blocking κ-opiate receptor (KOR) with a bolus injection of the KOR antagonist PF4455242 resulted in a significant increase in LH release and enhanced the stimulatory effect of senktide. These results support the hypothesis that KNDy neurons play a regulatory role in GnRH and hence gonadotropin secretion in sheep fetuses and serve as targets for negative feedback in males for maintaining a stable androgen environment crucial for brain masculinization. Supported by NIH Grant OD11047 to CER. Presentation: 6/1/2024

8624 Maternal ZIKV Infection Causes Oxidative Damage in Placenta of Both Female and Male Mice

Abstract Disclosure: V.M. Nascimento: None. I.S. Andrade: None. C.B. Andrade: None. R.S. Alves: None. R.P. Sousa: None. A.C. Valim: None. L.S. Dias: None. K.N. Fontes: None. I.F. Miranda: None. S.A. Coelho: None. L.B. Arruda: None. R.S. Fortunato: None. T.M. Ortiga-Carvalho: None. The placenta is a maternal-fetal organ with nutritional, exchanging, hormonal and protecting functions that are vital for fetal growth and development during gestation. However, these functions can be disturbed by vertically transmitted pathogens such as Zika virus (ZIKV). In 2015, ZIKV was responsible for an increasing number of newborns with congenital abnormalities in Brazil, known as Congenital Zika Syndrome (CZS). Nonetheless, the extension of ZIKV infection in the placenta, leading to CZS, is still unclear. It is known that ZIKV causes oxidative stress in trophoblasts. However, no one has ever studied placental oxidative stress caused by ZIKV infection in vivo. Here, we investigated whether maternal ZIKV infection could cause sex-specific oxidative stress in murine placenta. At gestational day (GD)12.5, pregnant mice (C57BL/6; 8-12 weeks old) were infected with ZIKV-BRPE243 (5x107 PFU; ZIKV group, n=22) or Mock (supernatants of noninfected C6/36 cells; control group, n=28). At GD18.5, c-section was performed and maternal spleens, placentas, fetuses and fetal brains were collected. We measured placental carbonylated protein levels (n=7), by 2D OxyBlot, nitrotyrosine residues (n=5), by immunohistochemistry, reduced thiol content (n=9), total superoxide dismutase (SOD; n=9) and total glutathione peroxidase (GPx; n=9) activities, by spectrophotometry. Data were analyzed by unpaired Student’s t test and Two-Way ANOVA with Tukey’s post test and represented as mean±SEM. ZIKV infection increased maternal spleen weight (p&amp;lt;0.0001) and decreased both female (p=0.0429) and male (p=0.0171) placental weight. Although placental weights were affected by the infection, female and male fetal weight and fetal crown-rump length were not changed. Conversely, maternal ZIKV infection increased only female fetal brain weight (p=0.0028). Moreover, we found that ZIKV infection increased nitrotyrosine residues in the placental labyrinth region of both female (p&amp;lt;0.0001) and male (p=0.0007) fetuses. Meanwhile, nitrotyrosine residues were increased by the infection only in the placental junctional zone of female fetuses (p=0.0131). Although ZIKV increased this oxidative damage biomarker, placental carbonylated protein levels were not changed by the infection in both sexes. Also, reduced thiol content and total SOD and GPx activities were not affected. Together, our data show that maternal ZIKV infection caused oxidative stress in both placental regions of female and male fetuses, as we saw that ZIKV increased oxidative damage, although antioxidant defenses were not changed by the infection, at least at term (GD18.5). ZIKV infection may have disturbed placental growth, as we found that placental weight was decreased in both sexes. Moreover, we believe that the increase in the female fetal brain weight could be a suggestive feature of cerebral edema or hydrocephalus. Presentation: 6/2/2024

8624 Maternal ZIKV Infection Causes Oxidative Damage in Placenta of Both Female and Male Mice

Abstract Disclosure: V.M. Nascimento: None. I.S. Andrade: None. C.B. Andrade: None. R.S. Alves: None. R.P. Sousa: None. A.C. Valim: None. L.S. Dias: None. K.N. Fontes: None. I.F. Miranda: None. S.A. Coelho: None. L.B. Arruda: None. R.S. Fortunato: None. T.M. Ortiga-Carvalho: None. The placenta is a maternal-fetal organ with nutritional, exchanging, hormonal and protecting functions that are vital for fetal growth and development during gestation. However, these functions can be disturbed by vertically transmitted pathogens such as Zika virus (ZIKV). In 2015, ZIKV was responsible for an increasing number of newborns with congenital abnormalities in Brazil, known as Congenital Zika Syndrome (CZS). Nonetheless, the extension of ZIKV infection in the placenta, leading to CZS, is still unclear. It is known that ZIKV causes oxidative stress in trophoblasts. However, no one has ever studied placental oxidative stress caused by ZIKV infection in vivo. Here, we investigated whether maternal ZIKV infection could cause sex-specific oxidative stress in murine placenta. At gestational day (GD)12.5, pregnant mice (C57BL/6; 8-12 weeks old) were infected with ZIKV-BRPE243 (5x107 PFU; ZIKV group, n=22) or Mock (supernatants of noninfected C6/36 cells; control group, n=28). At GD18.5, c-section was performed and maternal spleens, placentas, fetuses and fetal brains were collected. We measured placental carbonylated protein levels (n=7), by 2D OxyBlot, nitrotyrosine residues (n=5), by immunohistochemistry, reduced thiol content (n=9), total superoxide dismutase (SOD; n=9) and total glutathione peroxidase (GPx; n=9) activities, by spectrophotometry. Data were analyzed by unpaired Student’s t test and Two-Way ANOVA with Tukey’s post test and represented as mean±SEM. ZIKV infection increased maternal spleen weight (p&amp;lt;0.0001) and decreased both female (p=0.0429) and male (p=0.0171) placental weight. Although placental weights were affected by the infection, female and male fetal weight and fetal crown-rump length were not changed. Conversely, maternal ZIKV infection increased only female fetal brain weight (p=0.0028). Moreover, we found that ZIKV infection increased nitrotyrosine residues in the placental labyrinth region of both female (p&amp;lt;0.0001) and male (p=0.0007) fetuses. Meanwhile, nitrotyrosine residues were increased by the infection only in the placental junctional zone of female fetuses (p=0.0131). Although ZIKV increased this oxidative damage biomarker, placental carbonylated protein levels were not changed by the infection in both sexes. Also, reduced thiol content and total SOD and GPx activities were not affected. Together, our data show that maternal ZIKV infection caused oxidative stress in both placental regions of female and male fetuses, as we saw that ZIKV increased oxidative damage, although antioxidant defenses were not changed by the infection, at least at term (GD18.5). ZIKV infection may have disturbed placental growth, as we found that placental weight was decreased in both sexes. Moreover, we believe that the increase in the female fetal brain weight could be a suggestive feature of cerebral edema or hydrocephalus. Presentation: 6/2/2024

Prenatal Diagnosis and Clinical Outcomes of Isolated Mega Cisterna Magna.

Objective: The study aimed to investigate the clinical outcomes of fetuses diagnosed with isolated mega cisterna magna in utero. Methods: A multicenter retrospective cohort study was conducted across 18 university hospitals from 2010 to 2019. Cases diagnosed with isolated mega cisterna magna, defined as a cisterna magna >10 mm with a normal cerebellar vermis and no cystic dilation of the fourth ventricle, were included. Cases with other central nervous system (CNS) anomalies, extra-central nervous system anomalies, chromosomal abnormalities, or congenital infections were excluded. Maternal demographics, prenatal findings, delivery outcomes, and postnatal outcomes were analyzed. Results: The mean gestational age at initial diagnosis was 28.6 ± 3.9 weeks, and the mean anteroposterior diameter of the cisterna magna was 12.5 ± 3.2 mm. Of the 71 cases initially assessed, 48 (67.6%) showed self-regression in utero. Postnatally, 13 cases (18.3%) had persistent isolated mega cisterna magna, whereas 10 cases (14.1%) were diagnosed with other central nervous system anomalies. Among the persistent isolated mega cisterna magna cases, one child exhibited delayed neurodevelopment. There was a higher incidence of isolated mega cisterna magna in male fetuses, which exhibited a significantly larger mean cisterna magna diameter compared with female fetuses (P = .045). Conclusion: Male fetuses exhibited a higher incidence of isolated mega cisterna magna compared with female fetuses and had larger anteroposterior diameters of the cisterna magna. The study demonstrated favorable neurodevelopmental outcomes associated with isolated mega cisterna magna, with self-regression observed in two-thirds of the cases. However, consecutive prenatal and postnatal evaluations for additional central nervous system or extra-central nervous system malformations need to be performed, considering the differences between prenatal and postnatal diagnoses.

Intrauterine deaths - an unsolved problem in Polish perinatology.

The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

Maternal stress during pregnancy alters circulating small extracellular vesicles and enhances their targeting to the placenta and fetus

BackgroundMaternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as “stress signals” in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues.ResultsOur mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs.ConclusionOur results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes.

Impact of xylene exposure during organogenesis on foeto-placental efficiency and foetal viability: Exploring its association with oxidative stress-induced inflammation and apoptosis in utero.

The potential maternal and foetal toxicity resulting from exposure to xylene at or below the allowable limit of 100 ppm during gestation is not thoroughly studied. The aim of this study was to investigate maternal and foetal outcomes following prenatal exposure to xylene during organogenesis. Pregnant Sprague Dawley (SD) rats were administered intraperitoneal (IP) corn oil (vehicle), 100, 500, and 1000 parts per million (ppm) of xylene from gestational day (GD) 6 until GD17. Clinical signs, maternal weight gain, and food consumption were recorded daily. A caesarean hysterectomy was performed on GD21 to assess the reproductive and foetal outcomes. Exposure to 1000 ppm of xylene caused a significant decrease in the maternal body weight and food consumption, and an increase in intrauterine foetal deaths. Foetal assessment revealed a significant decrease in foetal weight in both male and female foetuses of female rats treated with 500 and 1000 ppm. Male placental weight was significantly decreased in all xylene-treated groups, while 1000 ppm xylene significantly decreased female placental weight. Histologically, marked uterine inflammatory lesions, fibrosis of the liver and renal tissues, as well as increased placental glycogen content were observed. Immunohistochemistry revealed a significant increase in lipid peroxidation and apoptotic markers. Thus, the foeto-maternal toxicities of xylene have been shown to be mediated by a systemic inflammatory response that exacerbates intrauterine oxidative stress and impairs foeto-placental transfer, leading to an increase in foetal mortality.

Anti-Müllerian hormone: biology and role in endocrinology and cancers.

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8th week of pregnancy, AMH is produced by Sertoli cells, and from the 23rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer's disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology.

Infracoccygeal/transperineal window: new method to prenatally diagnose and classify level of anal atresia.

To introduce a two-dimensional sonographic method to assess the fetal anus, and to evaluate the feasibility of this method to diagnose anal atresia prenatally and identify the presence or absence of anoperineal fistula (in males) and anovestibular fistula (in females). This was an observational study of suspected cases of anal atresia referred to a single center in Israel between August 2018 and October 2023. In addition to conventional evaluation of the perineum in the axial plane, fetuses referred to our center for suspected malformation were scanned with a new method termed the 'infracoccygeal/transperineal window'. This window consisted of a midsagittal view of the fetal pelvis, including the distal rectum and the anal canal. Normal anatomy was confirmed when the anal canal was continuous with the rectum and terminated at the expected location on the perineum. In female fetuses, the normal anal canal runs parallel to the vaginal canal and diverges posteriorly, terminating at the perineal skin, distant from the vestibule. In male fetuses, the normal anal canal diverges posteriorly in relation to the corpora cavernosa, terminating at the perineal skin, distant from the scrotum. High anal atresia was identified when a blind-ending rectal pouch was demonstrated in the pelvis without a fistula to the perineum or vestibule. Low anal atresia was determined when a rectal pouch was continuous with an anteriorly deflected fistula. In females, the fistula converges with the vaginal canal, terminating at the vestibule; in males, the fistula deflects anteriorly, terminating at the base of the scrotum. Postnatally, the diagnosis and type of anal atresia were confirmed through physical examination with direct visualization of the fistula, radiographic studies, surgical examination and/or postmortem autopsy. Of the 16 fetuses diagnosed prenatally with anal atresia, eight were suspected to have low anal atresia and eight were suspected to have high anal atresia. The median gestational age at diagnosis was 23 (range, 14-37) weeks. All cases showed additional structural malformation. Eleven patients opted for termination of pregnancy, of which four had low anal atresia and seven had high anal atresia. Postnatal confirmation was not available in four cases due to curettage-induced mutilation or in-utero degradation following selective termination of the affected twin, leaving 12 cases for analysis, of which seven were diagnosed with low anal atresia and five with high anal atresia. In these 12 cases, all prenatal diagnoses were confirmed as correct, rendering 100% sensitivity and 100% specificity in this high-risk fetal population. The infracoccygeal/transperineal window is an effective method to detect and classify the level of anal atresia prenatally. This may improve prediction of postnatal fetal continence and optimize prenatal counseling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective

IntroductionTonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.MethodAfter the antenatal diagnosis of...