Reproductive SciencesPub Date : 2025-02-01Epub Date: 2024-12-20DOI: 10.1007/s43032-024-01769-4
Rebecca L Wilson, Baylea N Davenport, Helen N Jones
{"title":"Mid-Pregnancy Placental Transcriptome in a Model of Placental Insufficiency with and without Novel Intervention.","authors":"Rebecca L Wilson, Baylea N Davenport, Helen N Jones","doi":"10.1007/s43032-024-01769-4","DOIUrl":"10.1007/s43032-024-01769-4","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) affects between 5-10% of all live births. Placental insufficiency is a leading cause of FGR, resulting in reduced nutrient and oxygen delivery to the fetus. Currently, there are no effective in utero treatment options for FGR, or placental insufficiency. We have developed a gene therapy to deliver, via a non-viral nanoparticle, human insulin-like 1 growth factor (hIGF1) to the placenta as a potential treatment for placenta insufficiency and FGR. Using a guinea pig maternal nutrient restriction (MNR) model of FGR, we aimed to understand the transcriptional changes within the placenta associated with placental insufficiency that occur prior to/at initiation of FGR, and the impact of short-term hIGF1 nanoparticle treatment. Using RNAsequencing, we analyzed protein coding genes of three experimental groups: Control and MNR dams receiving a sham treatment, and MNR dams receiving hIGF1 nanoparticle treatment. Pathway enrichment analysis comparing differentially expressed genelists in sham-treated MNR placentas to sham-treated Control revealed upregulation of pathways associated with degradation and repair of genetic information and downregulation of pathways associated with transmembrane transport. When compared to sham-treated MNR placentas, MNR + hIGF1 placentas demonstrated changes to genelists associated with transmembrane transporter activity including ion, vitamin and solute carrier transport. Overall, this study identifies the key signaling and metabolic changes occurring in the placenta contributing to placental insufficiency prior to/at initiation of FGR, and increases our understanding of the pathways that our nanoparticle-mediated gene therapy intervention regulates.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"435-443"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-16DOI: 10.1007/s43032-025-01792-z
Mehmet Başeğmez, Duygu Yüksel
{"title":"The Effect of Boric Acid on Oxidative Stress, Inflammation, and Apoptosis in Embryonic and Fetal Tissues Damage Caused by Consumption of High-Fructose Corn Syrup in Pregnant Rats.","authors":"Mehmet Başeğmez, Duygu Yüksel","doi":"10.1007/s43032-025-01792-z","DOIUrl":"10.1007/s43032-025-01792-z","url":null,"abstract":"<p><p>This study aimed to determine the protective role of boric acid in a pregnant rat model of high fructose corn syrup consumption. Consumption of high fructose corn syrup has been associated with adverse health outcomes in humans and animals. Twenty-eight healthy female Wistar albino rats (250-300 g weight and 16-24 weeks old) were randomly distributed into four equal groups (n = 7): Control, Boric acid (BA), High Fructose Corn Syrup (HFCS), HFCS + BA. Boric acid (20 mg/kg) was administered to pregnant rats via oral gavage every day during pregnancy. The prepared 30% HFCS (F30) solution (24% fructose, 28% dextrose) was added to the drinking water throughout pregnancy. At the end of pregnancy (day 19), blood, placenta, uterus, and fetuses were collected from rats. The results indicated that HFCS increases oxidative stress by increasing the level of MDA and decreasing GSH, SOD, and CAT activity in the blood of maternal. However, BA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). In addition, HFCS consumption significantly increased plasma TNF-α, IL-6, and leptin levels compared to control, BA, and HFCS + BA groups (p < 0.05). However, BA administration significantly decreased plasma TNF-α, IL-6, and leptin levels (p < 0.05). Furthermore, BA (20 mg/kg) significantly decreased HFCS-induced histopathological and immunohistochemical alterations in the placenta, uterus, and fetal tissue. In conclusion, BA may prevent HFCS toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat and alleviates histopathological and immunohistochemical changes. The findings indicate a need for further studies to assess the potential of boron in preventing or mitigating the effects of HFCS during pregnancy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"514-525"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2024-06-13DOI: 10.1007/s43032-024-01614-8
Jie Yang, Miaomiao Xu, Zun Wang, Man He, Gao Zhang, Lei Jin, Rongqian Zhao, Yiran Pan, Jiyu Tong, Li Nie
{"title":"Unraveling Estrogen and PCSK9's Roles in Lipid Metabolism Disorders among Ovariectomized Mice.","authors":"Jie Yang, Miaomiao Xu, Zun Wang, Man He, Gao Zhang, Lei Jin, Rongqian Zhao, Yiran Pan, Jiyu Tong, Li Nie","doi":"10.1007/s43032-024-01614-8","DOIUrl":"10.1007/s43032-024-01614-8","url":null,"abstract":"<p><p>We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"316-325"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-07DOI: 10.1007/s43032-024-01763-w
Giulia Emily Cetera, Camilla Erminia Maria Merli, Paolo Vercellini
{"title":"A Multimodal Approach to Symptomatic Endometriosis: A Proposed Algorithm for Clinical Management.","authors":"Giulia Emily Cetera, Camilla Erminia Maria Merli, Paolo Vercellini","doi":"10.1007/s43032-024-01763-w","DOIUrl":"10.1007/s43032-024-01763-w","url":null,"abstract":"<p><p>Recent research has proven that peripheral (PS) and central sensitization (CS), mental health, and myofascial dysfunction all play a role, alongside nociception, in the genesis and in the perpetuation of endometriosis' symptoms. However, such components of pain are still largely ignored in clinical practice, although not considering such contributors may entail serious consequences on women's health, including the choice of unnecessary surgery and leaving the real causes of pain untreated. At the present time, we are facing a paradox by which 25-40% of women who undergo laparoscopic surgery for pelvic pain do not have an obvious diagnosis, while the percentage of women with endometriosis who have signs of CS, of depressive or anxiety disorders, or who have an increased pelvic muscle tone ammounts to 41-55%, 15-88% and 28-73%, respectively. Moving from the widely-accepted stepwise approach suggested for endometriosis management, which consists in the initial prescription of low-dose combined oral contraceptives (COCs) or of a progestin monotherapy, followed by GnRH analogues and, ultimately, by surgery, when COCs and progestins have proven ineffective or are not tolerated or contraindicated, we propose an integration of such model which takes into account the identification and the simultaneous treatment of all pain contributors. Our objective is to encourage physicians' awareness of the need of a multidisciplinary, multimodal approach to endometriosis-related pain, and ultimately to promote a reduction in the number of unnecessary surgeries.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"289-299"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-17DOI: 10.1007/s43032-024-01755-w
Shaimaa Nasr Amin, Iman Aolymat, Sara Adel Hosny, Noha Samir Abdel Latif, Walaa Ibrahim, Asmaa Mohammed ShamsEldeen, Dalia Azmy Elberry
{"title":"Comparing the Effect of Heat Therapy and Mitochondrial-Targeted Antioxidants in Polycystic Ovarian Syndrome Phenotype Induced by Junk Food Consumption.","authors":"Shaimaa Nasr Amin, Iman Aolymat, Sara Adel Hosny, Noha Samir Abdel Latif, Walaa Ibrahim, Asmaa Mohammed ShamsEldeen, Dalia Azmy Elberry","doi":"10.1007/s43032-024-01755-w","DOIUrl":"10.1007/s43032-024-01755-w","url":null,"abstract":"<p><p>Polycystic ovarian syndrome (PCOS) is a complex endocrine-metabolic disorder, and multiple factors contribute to its pathophysiology. The current study assessed a PCOS-like animal model induced by consuming a high-fat sugar (HFHS) diet and compared the treatment outcome of mitochondrial-targeted antioxidants versus heat therapy. Sixty rats were divided into the following study groups: three control groups (negative and positive for the treatments used), HFHS, hot tub therapy (HTT) treatment, and MitoQ10 treatment (500 µmol/L MitoQ10 in clean drinking water daily, from week fourteen till week twenty-two of the study). At week fourteen, PCOS was confirmed by vaginal smear examination; measurements of blood testosterone (T), anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and insulin; and determination of the homeostatic model assessment of IR (HOMA-IR). At week 22, blood samples were collected for measurement of the serum LH, FSH, AMH, T, insulin, glucose, lipid profile, kisspeptin, ADAM metallopeptidase with thrombospondin type 1 motif 19 (ADAMTS19), S100 calcium-binding protein B (S100B), fibulin 1 (FBLN1), immunoglobulin free light chains (FLCs), kappa and lambda. Ovaries were examined for morphological changes; for the levels of glutathione (GSH), catalase, SOD, malondialdehyde (MDA), and nitric oxide (NO); and the expression of FK506 binding protein 52 (FKBP52) and the androgen receptor (AR). The consumption of HFHS diet-induced PCOS-like features, which have been ameliorated by both HTT and mitoQ10 as potential therapies, with MitoQ10 showing a superior effect over HTT.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"343-357"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-08DOI: 10.1007/s43032-024-01767-6
Satoshi Kanazawa, Yoko Awata
{"title":"Only Children by Choice vs. Only Children by Circumstances: Why Do Some Women Have Only One Child?","authors":"Satoshi Kanazawa, Yoko Awata","doi":"10.1007/s43032-024-01767-6","DOIUrl":"10.1007/s43032-024-01767-6","url":null,"abstract":"<p><p>In an attempt to stimulate further theory and research on only children, we introduce two conceptual distinctions: Only children as independent variables vs. only children as dependent variables; and only children by choice vs. only children by circumstances. What little scientific research exists on only children to date focuses almost exclusively on only children as independent variables and fails to make a distinction between only children by choice and only children by circumstances. A focus on only children by choice as dependent variables explores the question of why some women choose to have only one child. As an empirical illustration, analyses of prospectively longitudinal data with a nationally representative sample in the United Kingdom (National Child Development Study) show that women who experience pregnancy complications are significantly less likely to have another child and significantly more likely to have only one child. Our results suggest that increased chances of pregnancy complications that American women now experience alone can explain about 10% of the increase in the number of only children in the United States in the last half century. If certain genes incline women to have pregnancy complications, it is possible that only children by circumstances are genetically more similar to children with siblings than to only children by choice.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"526-534"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-16DOI: 10.1007/s43032-025-01785-y
Dimitrios Rafail Kalaitzopoulos, Ursula Catena, Alexandra Kohl Schwartz, Georgios Schoretsanitis, Brigitte Leeners, Panagiotis Drakopoulos, Nicolas Samartzis
{"title":"Chronic Endometritis and Endometriosis: Two Sides of the Same Coin?","authors":"Dimitrios Rafail Kalaitzopoulos, Ursula Catena, Alexandra Kohl Schwartz, Georgios Schoretsanitis, Brigitte Leeners, Panagiotis Drakopoulos, Nicolas Samartzis","doi":"10.1007/s43032-025-01785-y","DOIUrl":"10.1007/s43032-025-01785-y","url":null,"abstract":"<p><p>Both chronic endometritis and endometriosis are common entities in infertile patients. The association and the co-existence of these two entities are poorly evaluated. The aim of this systematic review and meta-analysis was to examine the association between chronic endometritis and endometriosis and to find the prevalence of chronic endometritis in women with endometriosis. A systematic electronic search was conducted using the MEDLINE, Scopus and Cochrane databases up to May 2022. Observational studies which examined the prevalence of chronic endometritis in women with endometriosis were included. Newcastle-Ottawa Scale was used for the quality assessment. Odds ratios (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and pooled prevalences with 95% CIs were calculated. 855 studies were identified, of which six studies were included in the systematic review and five in the meta-analysis. The prevalence of chronic endometritis in women with endometriosis was 28%, with higher frequency observed in women with endometriosis rASRM stage III-IV (43%) in comparison to women with endometriosis rASRM stage I-II (25%). The meta-analysis showed a significantly higher chronic endometritis in women with endometriosis in comparison to the control group (five studies, 264 endometriosis vs. 435 control, OR = 2.07; 95% CI 1.11-3.84, I<sup>2</sup> 43%, p = 0.02). The present meta-analysis showed a significantly higher risk of chronic endometritis in women with endometriosis in comparison to the control group. These findings contribute to a better understanding of the causes and consequences of endometriosis and chronic endometritis and may help in the development of more efficient treatment strategies for women with associated infertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"474-487"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-15DOI: 10.1007/s43032-024-01768-5
Christine Doran, Christy Pratt, Thomas Delate, Sonja Nazareth
{"title":"Methotrexate fixed dosing protocol for ambulatory treatment of ectopic pregnancy.","authors":"Christine Doran, Christy Pratt, Thomas Delate, Sonja Nazareth","doi":"10.1007/s43032-024-01768-5","DOIUrl":"10.1007/s43032-024-01768-5","url":null,"abstract":"<p><p>The primary objective of this study was to review a methotrexate 90-mg fixed-dose protocol for treatment of ectopic pregnancy, and to evaluate if any characteristics were associated with ectopic pregnancy treatment failure. This was a single arm retrospective cohort study conducted at Kaiser Permanente Colorado. The primary outcome was to describe rates of ectopic pregnancy treatment failure among patients who received fixed dose(s) of methotrexate for ectopic pregnancy between January 1, 2007 and August 31, 2017. Women were eligible for inclusion if they received outpatient treatment with methotrexate for an ectopic pregnancy during this time frame. Electronic administrative databases were queried to identify eligible patients and gather patient data, then patients were categorized based on success or failure of treatment. Ectopic pregnancy treatment failure was defined as the requirement for any additional intervention to terminate the pregnancy. A total of 259 patients were included in the final analysis. Overall, 210 (81.1%) ectopic pregnancies were successfully treated with methotrexate alone, and 49 (18.9%) required additional intervention. Baseline human chorionic gonadotropin (hCG) of less than 1000 mIU/ml was associated with treatment success (odds ratio for ectopic pregnancy treatment failure = 0.07 (95% confidence interval: 0.03-0.19)). Treatment of ectopic pregnancy with this fixed-dose methotrexate protocol is a reasonable alternative to weight-based dosing. Consistent with previously published studies, baseline hCG less than 1000 mIU/ml was associated with a high rate of treatment success.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"428-434"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-13DOI: 10.1007/s43032-024-01774-7
Vaibhav Gupta, Rashmi Srivastava
{"title":"Amelioration and Immuno-modulation by Ashwagandha on Wi-fi Induced Oxidative Stress in Regulating Reproduction Via Estrogen Receptor Alpha in Male Japanese Quail.","authors":"Vaibhav Gupta, Rashmi Srivastava","doi":"10.1007/s43032-024-01774-7","DOIUrl":"10.1007/s43032-024-01774-7","url":null,"abstract":"<p><p>As global change threatens avian biodiversity, understanding species responses to environmental perturbations due to radiation emitted by enormous increase in the application of wireless communication is very urgent. The study investigates the effect of MW radiation on redox balance, stress level, male fertility and the efficacy of Withania somnifera (WS) root extract (100 mg/kg body weight) orally administered in 8 weeks old mature male Japanese quail exposed to 2.4 GHz MW radiation for 2 h/day for 30 days with power density = 0.1264 mw/cm<sup>2</sup> and SAR = 0.9978 W/Kg. Wi-fi exposure induces a decrease in testicular weight, volume, density and gonado-somatic index (GSI) while Ashwagandha increases them. Oxidative stress parameters increased and activity of SOD, catalase, GSH was reduced in testes of exposed quail while Ashwagandha treatment reinstates the redox balance. Exposure to Wi-fi alters quail reproduction by increase in corticosterone and decreased testosterone with reduced expression of estrogen receptor alpha (ERα) in testis. Wi-fi exposure increases IL1β and reduces IL10 in testis. IL-1β inhibits testicular cell function and promotes apoptosis by increasing NF-κB and decreasing sperm count in exposed quails. Ashwagandha increases expression of ERα, sperm count and immunity in quail testis. Further, decrease in IL1β, NF-κB and increase in IL-10 after administration of Ashwagandha in Wi-fi exposed quail prevents inflammatory damages and enhances gonadal function. Thus, exposure to Wi-fi increases oxidative stress, activates apoptosis, modulates immunity in testis while Ashwagandha reverses them via enhanced ERα expression, increase in sperm count thereby enhancing fertility in male Japanese quail.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"455-466"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-02-01Epub Date: 2025-01-08DOI: 10.1007/s43032-024-01778-3
Craig C Ulrich, Lauren L Parker, Janet A Lambert, Lexa Baldwin, Iain L O Buxton, Neda Etezadi-Amoli, Normand Leblanc, Heather R Burkin
{"title":"Matrix Metallopeptidase 9 Promotes Contraction in Human Uterine Myometrium.","authors":"Craig C Ulrich, Lauren L Parker, Janet A Lambert, Lexa Baldwin, Iain L O Buxton, Neda Etezadi-Amoli, Normand Leblanc, Heather R Burkin","doi":"10.1007/s43032-024-01778-3","DOIUrl":"10.1007/s43032-024-01778-3","url":null,"abstract":"<p><p>Matrix metallopeptidase 9 (MMP9) is a secreted zinc-dependent peptidase known for extracellular remodeling. MMP9 is elevated in tissues from women experiencing preterm labor, and previous research has shown that the addition of combined matrix metallopeptidases 2 and 9 (MMP2/9) enhances uterine contractions. We hypothesized that adding MMP9 alone would enhance myometrial contractions and that specific MMP9 inhibition would suppress uterine contractions. In myometrial tissue from women undergoing term Caesarean sections, we observed an increased contractile response as measured by area under the curve over time in tissues treated with MMP9 compared to vehicle-treated controls (p = 0.0003). This effect was primarily due to increased contraction frequency in MMP9-treated tissues compared to controls (p < 0.0001). Specific inhibition of MMP9 with the highly selective MMP9 inhibitor 1 (AG-L-66085) reduced contractile responses in myometrial tissues from pregnant women. We observed a reduction in the oxytocin-induced contractile response as measured by area under the curve over time (p < 0.0001) and contraction amplitude (p < 0.0068) in AG-L-66085-treated tissues compared to vehicle-treated controls. To determine the effects of MMP9 inhibition in the absence of exogenous oxytocin, we tested the effects of AG-L-66085 on spontaneous contractions. The area under the curve (p = 0.0415) and amplitude (p = 0.0354) of spontaneous contractions were reduced in response to 1 μM AG-L-66085, and the inhibitory effects increased as the AG-L-66085 concentration increased. Together, these data support the hypothesis that elevated MMP9 promotes myometrial contractions and labor, while its inhibition promotes relaxation.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"444-454"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}