Uterine Weight Research Articles

Racial Disparities in Surgical Treatment of Uterine Fibroids During the COVID-19 Pandemic.

Objective: Analyze the association between race and surgery performed for uterine fibroids during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Retrospective exploratory cross-sectional study of patients with fibroids who underwent surgery during the COVID-19 pandemic. We compared the type of surgery performed (minimally invasive hysterectomy [MIH], uterine-sparing procedure [USP], or total abdominal hysterectomy [TAH]) by White versus non-White patients. Absolute percentage differences were estimated with multinomial logistic regression adjusting for age, body mass index (BMI), parity, comorbidities, and maximum fibroid diameter. Results: Of 350 subjects, the racial composition was 1.7% Asian, 23.4% Black, and 74.9% White. Non-White patients had greater fibroid burden by mean maximum fibroid diameter, mean uterine weight, and mean fibroid weight. Although MIH occurred more frequently among White patients (7.5% points higher [95% confidence interval (CI) = -3.1 to 18.2]), USP and TAH were more commonly conducted for non-White patients (3.4% points higher [95% CI = -10.4 to 3.6] and 4.2% points higher [95% CI = -13.2 to 4.8], respectively). The overall complication rate was 18.6%, which was 6% points lower (95% CI = -15.8 to 3.7) among White patients. Conclusion: During the COVID-19 pandemic at a single-site institution, non-White patients were more likely to undergo a uterine-sparing procedure for surgical treatment of uterine fibroids, abdominal procedures, including both hysterectomy and myomectomy, and experience surgery-related complications.

Impact of uterine weight on surgical outcomes in robotic hysterectomy: An ambispective analysis.

Robot-assisted surgeries are increasingly used for the treatment of benign gynaecological conditions. However, their impact in cases of significantly enlarged uteruses remains uncertain. This study aims to investigate whether the weight of the uterus influences the surgical results of robotic hysterectomy. Ambispective analysis of 306 cases was performed, of which 265 cases were analysed retrospectively. The outcome measures included total operative time, including docking time, console time and vault closure time, complication rates and quality of life (World Health Organization Quality of Life Brief questionnaire) stratified based on uterine sizes into three groups by every 250 g. Of the 306 cases, 76.47% of cases (n = 234) had uterine weight <250 g, 18.30% of cases (n = 56) had uterine weight between 250 and 500 g, while 5.23% of cases (n = 16) had a weight of uterine specimen >500 g. The total operative time was significantly lower in the <250 g group compared to >500 g (81.92 ± 22.81 vs. 111.88 ± 40.27 min; P = 0.003), contributed primarily by the console time. Although the need for post-operative blood transfusion was higher in the >500 g group, the overall complication rate between the three groups was similar. The three groups had comparable QOL through all four domains. The present study underscores the influence of uterine weight on robotic hysterectomy outcomes, revealing increased operative times and post-operative haemoglobin drop for uteri over 500 g. Despite these challenges, complications were not significantly affected by uterine size.

High-Volume Surgeons and Reducing Racial Disparities in Route of Hysterectomy

Study ObjectiveTo examine racial disparities in route of hysterectomy and perioperative outcomes before and after expansion of high-volume minimally invasive surgeons (>10 minimally invasive hysterectomies (MIH)/year) DesignRetrospective cohort study SettingMulti-center academic teaching institution PatientsAll patients who underwent a scheduled hysterectomy for benign indications during 2018 (pre-intervention) and 2022 (post-intervention) InterventionsRecruitment of Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)- trained faculty and increased surgical training for academic specialists in obstetrics and gynecology occurred in 2020. Measurements and Main ResultsPatients in the pre-intervention cohort (n=171) were older (median age 45 years vs. 43 years, p=0.003) while patients in the post-intervention cohort (n=234) had a higher burden of comorbidities (26% ASA class III vs. 19%, p=0.03). Uterine weight was not significantly different between cohorts (p=0.328). Between the pre-intervention and post-intervention cohorts, high-volume minimally invasive surgeons increased from 27% (n=4) to 44% (n=7) of those performing hysterectomies within the division and percentage of hysterectomies performed via minimally invasive route increased (63% vs. 82%, p<0.001). In the pre-intervention cohort, Black patients had a lower percentage of hysterectomies performed via minimally invasive route compared to White patients (Black = 56% MIH vs. White = 76% MIH, p=0.014). In the post-intervention cohort, differences by race were no longer significant (Black = 78% MIH vs. White = 87% MIH, p= 0.127). There was a significant increase (22%) in MIH for Black patients between cohorts (p<0.001). After adjusting for age, BMI, ASA class, prior surgery, and uterine weight, disparities by race were no longer present in the post-intervention cohort. Perioperative outcomes including length of stay (p<0.001), infection rates (p=0.002) and blood loss (p=0.01) improved post-intervention. ConclusionIncreasing FMIGs-trained gynecologic surgeons and providing more opportunities in robotic/laparoscopic training for academic specialists may improve access to MIH for Black patients and reduce disparities.

Association of maximum uterine diameter with postoperative complications in laparoscopic supracervical hysterectomy: A retrospective cohort study.

To determine the maximum uterine diameter threshold associated with an elevated risk of complications following laparoscopic supracervical hysterectomy (LSH). This was a retrospective cohort study from a single tertiary referral center. We enrolled patients who underwent LSH for benign indications at our hospital between January 2013 and June 2023. The primary outcome was the occurrence of surgical complications within the 30-day timeframe of hysterectomy. The covariate included the year of the procedure, patient age, body mass index, parity, American Society of Anesthesiologists classification, comorbidities, history of previous abdominal and pelvic surgery, and preoperative anemia, blood loss, surgical time, hospital stay and pathology. The exclusion criteria comprised those who underwent hysterectomy for malignancy, individuals who underwent total vaginal hysterectomy or laparoscopically assisted vaginal hysterectomy, and those with missing data on uterine maximum diameter, study outcomes, or covariates. We included a final sample of 120 patients, revealing a median uterine diameter of 9.12 cm, with 9.2% experiencing complications. The median uterine weight among 40 patients was 275 g. Receiver operating characteristic (ROC) curve analysis suggested a potential cutoff of 11.55 cm for predicting complications, with an area under the ROC curve of 0.67. Multivariate logistic regression confirmed a significant association between uterine diameter exceeding the cutoff and increased complication risk (OR 33.925, 95% CI: 2.294-501.690, P = 0.0103). A correlation (r = 0.762, P < 0.001) between uterine weight and diameter indicated the latter's suitability for preoperative assessment of uterine weight. The maximum uterine diameter with an optimal cutoff of 11.55 cm was associated with increased complication risk.

Vaginal assisted NOTES hysterectomy in The Netherlands; A prospective cohort study

ObjectivesVaginal assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) combines the benefits of vaginal and endoscopic surgery. This study presents the results of the first vaginal assisted NOTES hysterectomies (VANH) in The Netherlands. Study designA prospective cohort study was performed in two non-academic teaching hospitals in The Netherlands. Data was collected from patients who underwent a VANH for benign indications between August 2019 and April 2023. Baseline characteristics and data of intra- and postoperative surgical outcomes were recorded and analysed. The VANHs were performed by four experienced vaginal and endoscopic gynaecological surgeons. ResultsA total of 200 patients underwent a VANH. Indications were dysfunctional menstrual bleeding (61 %; n = 122), abnormal cervical cytology (15.5 %; n = 31), abdominal pain (11.5 %; n = 23), post ablation/sterilization pain syndrome (3.5 %; n = 7), uterine fibroids (5.0 %; n = 10), atypical endometrial hyperplasia (2.5 %; n = 5) and Lynch or BRCA gene mutation carriers (1.0 %, n = 2). The mean surgical time was 61.4 min ( ± 22.8 min) with a mean blood loss of 88 mL ( ± 89 mL) and a mean uterine weight of 150 g ( ± 112 g). In 2.0 % (n = 4) of the cases a conversion was necessary. Same day discharge (SDD) was feasible in 80.2 % (n = 105) of the patients planned in day-care. In 2.0 % (n = 4) an intra-operative complication and in 9.0 % (n = 18) a post-operative complication occurred. ConclusionThis study shows vNOTES to be a safe and feasible surgical technique and can be safely implemented with appropriate patient selection and skilled surgeons. It highlights the importance of surgeon awareness of the challenges inherent in the initial stages of the implementation of a new surgical technique when performing their first vNOTES procedures. Additional randomized clinical trials are needed to show superiority of vNOTES compared to traditional surgery.

Discovery and evaluation of novel spiroheterocyclic protective agents via a SIRT1 upregulation mechanism in cisplatin-induced premature ovarian failure

Currently, no effective treatment exists for premature ovarian failure (POF). To obtain compounds with protective effects against POF, we aimed to design and synthesize a series of spiroheterocyclic protective agents with a focus on minimizing toxicity while enhancing their protective effect against cisplatin-induced POF. This was achieved through systematic modifications of Michael receptors and linkers within the molecular structure of 1,5-diphenylpenta-1,4-dien-3-one analogs. To assess the cytotoxicity and activity of these compounds, we constructed quantitative conformational relationship models using an artificial intelligence random forest algorithm, resulting in R2 values exceeding 0.87. Among these compounds, j2 exhibited optimal protective activity. It significantly increased the survival of cisplatin-injured ovarian granulosa KGN cells, improved post-injury cell morphology, reduced apoptosis, and enhanced cellular estradiol (E2) levels. Subsequent investigations revealed that j2 may exert its protective effect via a novel mechanism involving the activation of the SIRT1/AKT signal pathway. Furthermore, in cisplatin-injured POF in rats, j2 was effective in increasing body, ovarian, and uterine weights, elevating the number of follicles at all levels in the ovary, improving ovarian and uterine structures, and increasing serum E2 levels in rats with cisplatin-injured POF. In conclusion, this study introduces a promising compound j2 and a novel target SIRT1 with substantial protective activity against cisplatin-induced POF.

Evaluating for Racial Disparities in the Utilization of Minimally Invasive Hysterectomy for the Treatment of Uterine Leiomyoma

Introduction: Minimally invasive hysterectomy (MIH) for benign gynecologic indications has many patient advantages over traditional abdominal hysterectomy (AH) including decreased hospital stay, decreased mortality, and faster recovery. Although MIH has been shown to improve outcomes as compared with abdominal hysterectomy, racial and socioeconomic disparities can impact patient access to the minimally invasive procedure. Previous studies have demonstrated that Black and Hispanic-identifying patients are significantly less likely to receive a MIH when compared to White patients. One proposed contributor to this finding is the higher rate and delayed diagnosis of uterine leiomyoma in Black patients compared to White patients. This disparity could delay diagnosis, and cause a larger leiomyoma necessitating use of abdominal hysterectomy. Another explanation in disparity is the physician training at hospitals in underserved areas. This study aims to investigate if race impacts access to MIH for leiomyoma at Carle Foundation Hospital in Urbana, Illinois. Methods: This retrospective analysis studied patients from 2011-2020 who received a hysterectomy at Carle Foundation Hospital for a primary diagnosis of leiomyoma. MIH included laparoscopic, vaginal, and robotic-assisted. Hysterectomies for malignancy were excluded. The demographic data included age, race, body mass index (BMI), type of hysterectomy, insurance, history of previous obstetric and abdominal surgeries, and uterine weight. The race categories included White, Black, and Others. Hispanic and Asian patients were placed into the other category due to the limited sample size. Descriptive statistics were used to evaluate the demographic data. Odd ratios were calculated to determine if a patient received a MIH over an AH based on race. An adjusted odds ratio was calculated to account for BMI, uterine weight, history of cesarean section, and previous abdominal surgery. Results: A total of 324 hysterectomies from 2011-2020 were performed for leiomyoma. Abdominal hysterectomies accounted for 32.1% and MIH accounted for 68.9%, with 7.4% being laparoscopic, 5.6% being vaginal, and 55.9% being robotic-assisted. The average age of White patients was 46.7 years old, and was higher than Black patients, 43.6 years old (p&lt;.01). The average BMI of Black patients was 34.6 kg/m2, and was higher than White patients, 30.3 34.6 kg/m2 (p&lt;.01). More White patients had commercial insurance at 83.5% compared to Black patients at 48.1% (p&lt;.01). More Black patients had Medicaid or Medicare at 50.6% compared to White patients at 14.8% (p&lt;.01). Black patients had an average uterine weight at 579.8g compared to White patients at 438.6g (p&lt;.05). The majority (73.7%) of White patients received a MIH, with 26.3% receiving an AH. Forty five percent of Black patients received an AH while 54.5% received a MIH. Conclusion: At Carle Foundation Hospital during the years 2011-2020, a lower percentage of African American patients, compared to white patients, received a minimally invasive hysterectomy in the treatment of uterine leiomyoma. Further analysis will investigate for the odds ratios of each group receiving a MIH and will adjust for BMI, uterine weight, obstetric and abdominal surgical history.

Exploring Hyperprolific Sows: A Study of Gross Morphology of Reproductive Organs and Oxytocin Receptor Distribution across Parities.

This study investigated the gross morphology of reproductive organs and oxytocin receptor distribution across different parities in hyperprolific sows. A total of thirty-two reproductive organs from Landrace × Yorkshire crossbred sows were categorized into three groups based on parity numbers: 1 (n = 10), 2-5 (n = 12), and ≥6 (n = 10). All sows were culled due to management problems, and none had reproductive disorders. A gross morphology examination of the ovaries, uterus, and the rest of the reproductive tract was conducted. Using immunohistochemistry, the levels of oxytocin receptor were evaluated in five layers of the uterus, the epithelial, superficial glandular, deep glandular, and circular and longitudinal smooth muscles of the myometrium, and were quantified using an H-score. On average, the age and body weight of sows and the total number of piglets born per litter were 799.8 ± 327.8 days, 213.2 ± 31.7 kg, and 15.5 ± 4.8, respectively. The numbers of ovulations in sows in parity number 1 (19.9 ± 2.4) were lower than those in sows in parity numbers 2-5 (29.7 ± 2.0, p = 0.004) and ≥6 (27.7 ± 2.1, p = 0.022). The uterine weights of sows in parity number 1 (902.9 ± 112.5 g) were lower than those of parity numbers 2-5 (1442.1 ± 111.8 g, p = 0.001) and ≥6 (1394.3 ± 125.1 g, p = 0.004). The length of the uterus in sows with parity number 1 (277.9 ± 26.1 cm) was shorter than those in sows with parity numbers 2-5 (354.6 ± 25.9 cm, p = 0.033) and tended to be shorter than those in sows with parity numbers ≥ 6 (346.6 ± 29.0 cm, p = 0.068). The immunolocalization of oxytocin receptors could be detected in various parts of the porcine endometrium and myometrium. Among the five tissue layers of the uterus, the H-score of oxytocin receptors in the deep uterine glands was greater than in the superficial uterine glands (p = 0.023) and the circular muscle layer of the myometrium (p = 0.011), but it did not differ from the epithelial layer of the endometrium (p = 0.428) or the longitudinal muscle layer of the myometrium (p = 0.081). Sows with parity numbers ≥ 6 had a lower oxytocin receptor H-score than those with parity numbers 1 (p < 0.001) and 2-5 (p < 0.001). In conclusion, these data emphasize the notable variations in several reproductive parameters and the levels of oxytocin receptor within the uterus of hyperprolific sows. Across the majority of uterine tissue layers, there was a marked decrease in the H-score of the oxytocin receptor in the older sows.

Protective effects of probiotics against menopausal symptoms in ovariectomized mice

With growing interest in the role of the gut microbiome in the pathogenesis of menopausal disorders, probiotic supplementation is emerging as a novel therapeutic strategy for postmenopausal women. In this study, we investigated the protective effects of several probiotic strains against menopausal symptoms using an ovariectomized (OVX) mouse model fed a high-fat diet, in comparison with the effects of 17β-estradiol (E2) replacement. Among the eight tested probiotic strains, we selected four (Limosilactobacillus fermentum MG901, Lactiplantibacillus plantarum MG4604, Ligilactobacillus salivarius MG4679, and Lacticaseibacillus reuteri MG5463) that showed superior estrogen-like activity in an uterotrophic assay. We then examined their effects in OVX mice. The probiotic MG4679 was tested in combination with MG5463. During the 12-week experimental period, oral administration of the four probiotics reduced blood glucose and body temperature and ameliorated depression-like behavior in OVX mice. In the Barnes maze test, MG901 and MG4604 improved the spatial memory deficits observed in OVX mice. Micro-CT analysis of mouse femurs revealed that MG5463 prevented the OVX-induced reduction in cortical bone mineral density and bone volume fraction. Importantly, similar to E2 replacement, most of the test probiotics increased Akt phosphorylation in skeletal muscle, estrogen receptor-α (ER-α) protein expression in the liver, and ERK phosphorylation in the brain of OVX mice. However, unlike E2 treatment, all probiotics did not affect uterine weight, uterine ER-α expression, and serum E2 concentration. These results indicated that the probiotics used in this study exhibited protective effects against menopausal symptoms, partly through estrogen-mimetic action, without unfavorable uterine stimulation in OVX mice.

Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1β signalling pathway and gut-bone axis

Aim of the studyThis study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the “Gut-Bone Axis”. Material and methodsThe impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. ResultsEFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1β signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. ConclusionsOur study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.

Estrous cycle and uterine weight of ovariectomized menopause female rat models after treatment with Leucaena leucocephala (Lam.) de Wit leaf extract

Highlights:1. This study found that Leucaena leucocephala leaf ethanol extract has the ability to stimulate the growth of vaginal epithelial cells in ovariectomised rats.2. Leucaena leucocephala leaf extract can be developed as a safe and cost-effective natural alternative for hormone replacement therapy in premenopausal women and livestock. Highlights:1. This study found that Leucaena leucocephala leaf ethanol extract has the ability to stimulate the growth of vaginal epithelial cells in ovariectomised rats.2. Leucaena leucocephala leaf extract can be developed as a safe and cost-effective natural alternative for hormone replacement therapy in premenopausal women and livestock. Abstract Hormone replacement therapy has adverse effects that may cause additional health problems, such as hot flashes, cancer, ischemic stroke, and death. Phytoestrogen is an alternative ingredient used for hormone replacement therapy with less risk. The Leucaena leucocephala (Lam.) de Wit plant is widely used as a medicinal ingredient and animal feed. This study aimed to determine the effect of Leucaena leucocephala leaf extract on the uterine weight and estrous cycle of ovariectomized rats. This research used a completely randomized control design, which included two treatment groups (P1 and P2) and two control groups (negative (K-) and positive (K+)) with six replications in each group (n=24). The negative control (K-) was given 2 mL of corn oil, while K+ received 0.1 mg/kg bw of 17β-estradiol. P1 and P2 were administered 250 and 300 mg/kg bw of Leucaena leucocephala leaf extract, respectively. The extract was administered daily by gavage for 30 days. Estrous cycle data were obtained on day 31 by previously collecting vaginal swabs twice a day for 15 days. After the rats were sacrificed under anesthesia using chloroform, they underwent surgery to remove the uterine organs for weight measurement. The data were analyzed for normality and homogeneity using the Shapiro-Wilk and Levene tests. The data distribution were not normal, so the Kruskal Wallis test was used to test the hypothesis. If there was a difference between controls and treatments, the analysis continued with the Mann-Whitney test (p&lt;0.05). The controls and treatments exhibited a significant difference in the length of each phase and overall estrous cycle. The post hoc Duncan test revealed that the highest uterine weight was found in 17β-estradiol treated rat. It was significantly different with both extracts treated rats. Both extract effect on uterine weight were not significantly difference. In conclusion, administering Leucaena leucocephala leaf extract results in an increased uterine weight and a normal estrous cycle in ovariectomized rats.

The impact of heterotopic ovarian tissue transplantation with varied volumes on reproductive endocrine function in oophorectomized rats

Background This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. Methods Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10−4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. Results Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. Conclusion The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.

Disrupted one-carbon metabolism in heifers negatively affects their health and physiology.

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ± 12.6kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.

Subacute exposure to DEHP leads to impaired decidual reaction and exacerbates the risk of early miscarriage in mice.

To investigate the effect of subacute exposure of Di (2-ethylhexyl) phthalate (DEHP) on endometrial decidualization and early pregnancy miscarriage in mice. CD1 mice were orally administrated with 300 (low-dose group), 1000 (medium-dose group), or 3000 mg·kg－1·d－1 DEHP (1/10 LD50, high-dose group) for 28 days, respectively. An early natural pregnancy model and an artificially induced decidualization model were established. The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization, respectively. The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining, Masson staining, TUNEL assay, and Western blotting. A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg－1·d－1 DEHP, and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation. Compared with the control group, the conception rate was significantly decreased in the high-dose DEHP subacute exposure group (P<0.05). HE staining showed that, compared with the control group, the decidual stromal cells in the low- and medium-dose exposure groups were disorganized, the nuclei of the cells were irregular, the cytoplasmic staining was uneven, and the number of polymorphonuclear cells was significantly reduced. Masson staining showed that compared with the control group, the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed, more abundant and more disorderly. TUNEL assay showed increased apoptosis in the decidua area compared to the control group. Western blotting showed that the expression of BMP2, a marker molecule for endometrial decidualization, was significantly reduced (P<0.05 or P<0.01). The abortion rate and embryo resorption rate were increased, and the number of embryos, uterine wet weight, uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone, an abortifacient drug (P<0.05 or P<0.01). Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.

Prenatal exposure to ethion caused maternal and foetal toxicity in rats

Ethion is a class II moderately toxic organothiophosphate pesticide. The main objective of this study was to evaluate the maternal and foetal toxicity of ethion in rats. Pregnant rats were divided into 5 groups. Group I served as control. Group II, III, IV, and V were orally administered with 0.86, 1.71, 3.43, and 6.9 mg/kg of ethion respectively, from gestational day (GD) 6–19. Dams were sacrificed on GD 20. Maternal toxicity was assessed by body weight gain, foetal resorptions, oxidative stress, liver and kidney function tests, and histopathology. Foetal toxicity was assessed by physical status, gross, teratological and histopathological examination. Ethion caused dose-dependent reduction in maternal body weight gain, increased resorptions, and reduced gravid uterine weights. Elevated MDA levels and altered levels of GSH, SOD and catalase were recorded in pregnant dam serum and tissues. SGOT, SGPT, total bilirubin, urea, uric acid, and creatinine were elevated in ethion groups indicating liver and kidney toxicity. Histology of uterus revealed myometrial degeneration and mucosal gland atrophy in uterus of pregnant dams and degenerative changes in placenta. It showed histological alterations in liver, kidney, and lungs. There was reduction in the foetal body weights and placental weights, and degenerative changes in the foetal liver and kidney. Gross evaluation of foetuses showed subcutaneous hematoma. Skeletal evaluation showed partial ossification of skull bones, costal separation, and agenesis of tail vertebrae, sternebrae, metacarpals and metatarsals. The findings reveal that prenatal exposure to ethion caused maternal and foetal toxicity in rats.

Nandrolone treatment of adolescent female rats alters reproductive tissue and gonadal steroid profile

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly AAS used by young adults is nandrolone. In the USA, more than 20 % of AAS users started using steroids before the age of 20. This is alarming as most female users are unaware of the detrimental reproductive effects of AAS use such as amenorrhea, anovulation and clitoromegaly. An additional detrimental effect of AAS is their addictive liability. Previous studies indicate that animals self-administer AAS. Furthermore, AAS can cross-sensitize with other drugs of abuse such as cocaine. Our goal was to elucidate the effects of both AAS and cocaine in the reproductive system of female rats. Our hypothesis is that AAS will have a detrimental effect on the reproductive system of female rats. Adolescent female rats were divided into two large groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. Animals were further subdivided into groups that received saline or cocaine injections (0.01cc/10g) for a total of 4 groups: Oil-Saline, ND-Saline, Oil-Cocaine and ND-Cocaine. One cohort (Day 40) received cocaine or saline injections (0.01cc/10g) from days 40 to 44 and on days 52 and day 62. The other cohort (Day 65) received cocaine or saline injections from days 65 to 69 and on days 77 and 87. Our data show that administration of nandrolone during adolescence increased body weight of female rats. Ovarian weight was decreased, and ovarian tissue presented multiple cysts with fewer follicles. Nandrolone also disrupted uterine morphology. The uterine lumen was increased, the endometrial thickness reduced and thickness of myometrial tissue, as well as uterine weight, was increased. In addition, nandrolone reduced both endometrial estrogen and androgen receptors, an effect lost by day 88. In contrast, uterine tissue at day 63 showed an increase in progesterone receptor (PR) immunoreactivity, whereas PR immunoreactivity decreased in tissue obtained at Day 88 regardless of whether animals had received cocaine. Cocaine also increased PR receptors in uterine tissue at day 63 and 88. Animals treated with nandrolone had higher serum concentrations of testosterone and estradiol and a lower level of progesterone. These data show that nandrolone when administered in supraphysiologic doses during adolescence, has long lasting effects on the reproductive system of the female rat due to the depot effects and long half-life of this drug. These data warrant further research in this area to determine the long-term consequences of early nandrolone exposure on the female reproductive system, as well as fertility. Financial assistance was provided by the Offce of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE-#1545803). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Infertility in POMC-deficient mice

The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and its product is cleaved into several peptides including the melanocyte stimulating hormones (α, β, or γ-MSH), adrenocorticotropic hormone (ACTH), and beta-endorphin. Alpha-MSH is involved in regulating appetite, sexual behavior, and melanin, while ACTH regulates secretion of glucocorticoids from the adrenal cortex. Humans who have a POMC mutation either produce an abnormally short version of POMC or are missing the protein completely and therefore lack these hormones. This has biological consequences including red hair and fair skin, early-onset obesity (due to severe hyperphagia), and potentially hypothyroidism, hypogonadism, and infertility. Many of these same effects are seen with mice containing this deficiency. We are interested in studying infertility through a mouse model of hypothalamic-specific POMC-deficiency. These mice also experience early-onset obesity and infertility. Estradiol is a key reproductive hormone that is essential for fertility. POMC deficiency may lead to hypogonadism, which can cause low levels of estrogen so we hypothesize that POMC-deficient mice have reduced estrogen levels, which may contribute to their infertility. To test this hypothesis, we will measure estrogen levels in POMC-deficient mice at different stages of the estrus cycle using an estradiol ELISA kit. We expect the POMC-deficient mice to have lower estrogen levels than control mice. We also plan to use liquid chromatography mass spectrometry (LC-MS) to measure estrogen levels. Before collecting the blood samples, vaginal cell samples are obtained and viewed under a microscope to analyze the ratio of cells and determine which stage the females were in—proestrus, estrus, metestrus, or diestrus. Blood samples are then collected into 1.5 mL microcentrifuge tubes with 10 microliters of 0.5 M EDTA to prevent blood clotting. After blood is collected, it is centrifuged at 2,000 g for 20 minutes at 4 degrees Celsius. The plasma is then stored at -80 degrees Celsius until analysis. Based on preliminary results we expect the POMC deficient mice to have reduced estrogen and/or altered levels throughout the cycle. So far, our results have indicated that POMC-deficient female mice have abnormal estrus cycles and also reduced uterine weights. The conclusions from this study will help us understand more about the causes of infertility in POMC-deficient mice, which may also lead to greater understanding on how to treat humans with infertility due to a POMC mutation. Support for this research was provided by IRACDA grant NIHK12GM111725 to Z.T. and UVU Scholarly Activities Grant to A.G. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Estrogen Regulation of PAD2 and Citrullination in the Aging Female Heart

Advanced age is the primary risk factor for heart failure, an enormous public health burden. With aging, men tend to develop systolic dysfunction whereas women are predisposed to develop diastolic dysfunction. Despite these known phenotype differences, underlying molecular mechanisms of sex differences in cardiac aging are unknown. Citrullination, a post-translational modification catalyzed by the peptidylarginine deiminases (PAD) enzyme family, is positively regulated by the sex hormone estrogen (E2) suggesting a potential novel mechanism of age-related cardiac functional changes in women. We hypothesized that PAD expression and citrullination are sexually dimorphic with aging such that as E2 levels decline, so too does citrullination, thus contributing to diastolic dysfunction. We quantified expression of PAD2, the primary cardiac isoform, in female young reproductively competent adult (3 months) and aged (21 months) C57Bl6 mice. Consistent with clinical reports, in our model of aging, female mice developed diastolic dysfunction, with a prolonged linear phase relaxation (54.0 ± 1.7 msec, adult and 66.0 ± 3.3 msec aged, p&lt;0.05). PAD2 expression decreased with age in the female heart, concomitant with decreases in myocardial protein citrullination. To identify potential mechanisms of differential citrullination by age, we performed cit-mass spectrometry. Adult female mice had higher overall citrullination patterns than aged females with enrichment of citrullinated proteins in metabolic, mitochondrial, and sarcomeric pathways. In reproductively competent adult females, cardiac PAD2 expression was higher during estrus compared to diestrus. To confirm direct regulation of PAD2 by E2, a cohort of adult mice underwent ovariectomy (OVX) with or without E2 replacement, provided orally in the water (0.5μM E2) for three weeks. Exogenous E2 supplementation post-OVX increased uterine weight and PAD2 expression, further confirming positive regulation by E2. Together, we suggest that hormonally regulated changes in PAD2 and citrullination with age contribute to sex-specific cardiac aging. Ongoing experiments will directly test the role of PAD2 in the heart by generation of a novel myocyte specific PAD2 deleted mouse across the female lifespan. This abstract was made possible by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under 2P20GM103432. This work was supported by the National Institutes of Health [K01 AG058810 DRB, [K01 AG066845 KCW]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ethanolic extract of Persea americana Mill. (Lauraceae) seeds induced antiestrogenic effects in young female Wistar rats.

The ethanol extract of Persea americana seeds was found to inhibit the development of estrogen-dependent conditions in female Wistar rats, suggesting the ability of its secondary metabolites to interact with estrogen receptors (ERs), either as partial agonists or as antagonists. To test this hypothesis, the abovementioned extract was assessed for its ability to mimic and/or antagonize estradiol effects. Two experiments were conducted in ovariectomized (OVX) rats: (1) animals were treated with estradiol valerate (E2V; 1 mg/kg) or P.americana at doses of 25 and 50 mg/kg; (2) animals were treated with E2V alone (0.75 mg/kg) or in combination with P.americana at the abovementioned doses. Treatments were given orally for 3days and animals were sacrificed for biochemical and histological analyses of the uterus and vagina. When administered alone, P.americana did not change the histomorphology of both organs (uterus and vagina). In combination with E2V, P.americana decreased uterine weight [30 % decrease (p<0.001) at 25 mg/kg and 24 % (p<0.01) at 50 mg/kg] and epithelium height (37 % decrease). This was associated with decreased estradiol levels (at least 86 % decrease, p<0.001) in the uterus. Similarly, vagina epithelium height decreased by at least 34 % (p<0.05) when E2V was co-administered with P.americana. The seed extract of P.americana contains ER antagonist secondary metabolites accounting for its ability to inhibit the development of estrogen-dependent conditions in female rats.

Estrone-mediated lowering of ROS and NOX4 improves endothelial function in ovariectomized wistar rats.

Estrone (E1) constitutes the primary component in oral conjugated equine estrogens (CEEs) and serves as the principal estrogen precursor in the female circulation in the post-menopause. E1 induces endothelium-dependent vasodilation and activate PI3K/NO/cGMP signaling. To assess whether E1 mitigates vascular dysfunction associated with postmenopause and explore the underlying mechanisms, we examined the vascular effects of E1 in ovariectomized (OVX) rats, a postmenopausal experimental model. Blood pressure was measured using tail-cuff plethysmography, and aortic rings were isolated to assess responses to phenylephrine, acetylcholine (ACh), and sodium nitroprusside. Responses to ACh in rings pre-incubated with superoxide dismutase (SOD), catalase (CAT), or apocynin were also evaluated. Protein expression of SOD, CAT, NOX1, NOX2, and NOX4 was determined by Western blotting. E1 treatment resulted in decreased body weight and retroperitoneal fat, increased uterine weight, and prevented elevated blood pressure in the OVX group. Furthermore, E1 improved endothelium-dependent ACh vasodilation, activated compensatory antioxidant mechanisms - i.e. increased SOD and CAT antioxidant enzymes activity, and decreased NOX4 expression. This, in turn, helped prevent oxidative stress and endothelial dysfunction in OVX rats. Additionally, E1 treatment reversed the increased total LDL cholesterol observed in the OVX group. The findings underscore protective effects of E1 on the cardiovascular system, counteracting OVX-related oxidative stress and endothelial dysfunction in Wistar rats. E1 exhibits promising therapeutic benefits for managing cardiovascular health, particularly in postmenopausal conditions.