Reproductive Sciences最新文献_第10页

Matrix Metallopeptidase 9 Promotes Contraction in Human Uterine Myometrium. 基质金属肽酶9促进人子宫肌层收缩。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2025-01-08 DOI: 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":"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.","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}

引用次数: 0

A 12-h Difference in Exogenous Progesterone Initiation Does Not Have an Impact on Ongoing Pregnancy Rates in Artificial Cycles, as Long as Luteal Phase Support Starts Five Days Before Blastocyst Transfer. 只要在囊胚移植前5天开始黄体期支持，外源性黄体酮起始12小时的差异对人工周期的妊娠率没有影响。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-12-23 DOI: 10.1007/s43032-024-01759-6

Cristina Rodríguez-Varela, Maria Salvaleda-Mateu, Ernesto Bosch, Elena Labarta

{"title":"A 12-h Difference in Exogenous Progesterone Initiation Does Not Have an Impact on Ongoing Pregnancy Rates in Artificial Cycles, as Long as Luteal Phase Support Starts Five Days Before Blastocyst Transfer.","authors":"Cristina Rodríguez-Varela, Maria Salvaleda-Mateu, Ernesto Bosch, Elena Labarta","doi":"10.1007/s43032-024-01759-6","DOIUrl":"10.1007/s43032-024-01759-6","url":null,"abstract":"Purpose: To elucidate if morning or evening start of exogenous progesterone (P4) five days before blastocyst embryo transfer (ET) impacts ongoing pregnancy rates (OPR) in artificial cycles.Methods: Single-centre retrospective cohort study of 6493 artificial cycles for an ET (oestrogens and luteal phase support [LPS] with micronized vaginal progesterone [MVP] 400 mg/12 h), conducted at an infertility clinic, December 2018-July 2022. LPS was given from five days before ET. Until March 2021, LPS was started in the evening of day 0 of P4 exposure (\"evening start\"); since April 2021, LPS was started in the morning of day 0 (\"morning start\").Results: Morning start of LPS (n = 2482 cycles); evening start (n = 3983 cycles). Morning or evening start did not exert any impact in OPR (46.9% vs. 46.3%, p = 0.682), as well as after adjusting for any potential confounders (aOR (95%CI): 1.00 (0.89-1.13); p = 0.996). Regarding serum P4 levels, no differences were found between morning (13.4 ± 5.8 ng/ml) and evening start of LPS (13.2 ± 6.4 ng/ml; p = 0.181). However, suboptimal serum P4 levels on the ET day (< 8.8 ng/ml) were registered in 16.6% (n = 411) vs. 19.8% (n = 788) of cycles with a morning and evening start, respectively (p = 0.001).Conclusions: A 12-h difference in exogenous P4 initiation does not exert an impact on pregnancy outcomes in artificial cycles with MVP, as far as it is started five days before ET. Results from this study offer a great advantage in patient management, by being able to start LPS either in the morning or in the evening five days before blastocyst transfer.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"488-494"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882887","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}

引用次数: 0

The Relationship Between the Average Decreased Times of Estradiol and Early Miscarriage: An Observational Study. 雌二醇平均下降时间与早期流产之间的关系：观察研究。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-05-06 DOI: 10.1007/s43032-024-01570-3

Fangxiang Mu, Chen Wang, Xiaofeng Li, Fang Wang

{"title":"The Relationship Between the Average Decreased Times of Estradiol and Early Miscarriage: An Observational Study.","authors":"Fangxiang Mu, Chen Wang, Xiaofeng Li, Fang Wang","doi":"10.1007/s43032-024-01570-3","DOIUrl":"10.1007/s43032-024-01570-3","url":null,"abstract":"Decreased estradiol (E2) levels are associated with early miscarriage (EM), but the relationship between decreased times of E2 and EM has not been reported. We aimed to investigate the relationship between the average decreased times of E2 (ADTE) and EM. Women with a history of miscarriage were retrospectively recruited from the Reproductive Center of Lanzhou University Second Hospital (Lanzhou, China) between September 2019 and February 2022. Based on pregnancy outcome, they were divided into ongoing pregnancy group (n = 359) and EM group (n = 104). In addition, subgroup analyses were performed for the number of previous miscarriages and whether E2 levels decreased continuously. The exposure and outcome variables were ADTE and miscarriage before 12 weeks of gestation, respectively. Totally, 1171 patients were recruited and 463 patients were finally analyzed. ADTE was associated with EM (odds ratio [OR] = 1.346, 95% confidence interval [CI]1.154-1.571, P < 0.001). When ADTE ≥ 2.5, the EM risk increased 1.17-fold compared to patients with 0-1.249 times (OR = 2.170, 95% CI 1.144-4.117, P = 0.018). Moreover, a threshold effect existed in the ADTE and the risk of EM with a value of 4.9 times. When exceeding 4.9 times, the EM risk increased 4.713-fold for each increased unit (OR = 5.713, 95% CI 1.255-23.170, P = 0.024). Subgroup analysis showed that ADTE had a greater effect on the occurrence of EM in women with a history of 1-2 miscarriages than in women with 3 miscarriages. Decreased E2 was a risk factor for EM regardless of whether it dropped continuously or not. In conclusion, our study identifies a potential link between ADTE and early miscarriage risk in women with prior miscarriages, yet cautious interpretation is necessary due to inherent design limitations. Further research with prospective designs and large population samples is essential to validate ADTE's utility as a predictive indicator for early miscarriage in clinical settings.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"358-365"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868070","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}

引用次数: 0

Association of Parity with Type 2 Diabetes Mellitus in Japan. 日本胎次与2型糖尿病的关系

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-12-11 DOI: 10.1007/s43032-024-01752-z

Hongxin Wang, Noriyuki Iwama, Keiichi Yuwaki, You Nakamichi, Hirotaka Hamada, Hasumi Tomita, Kazuma Tagami, Rie Kudo, Natsumi Kumagai, Hirohito Metoki, Naoki Nakaya, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Masatoshi Saito

{"title":"Association of Parity with Type 2 Diabetes Mellitus in Japan.","authors":"Hongxin Wang, Noriyuki Iwama, Keiichi Yuwaki, You Nakamichi, Hirotaka Hamada, Hasumi Tomita, Kazuma Tagami, Rie Kudo, Natsumi Kumagai, Hirohito Metoki, Naoki Nakaya, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Masatoshi Saito","doi":"10.1007/s43032-024-01752-z","DOIUrl":"10.1007/s43032-024-01752-z","url":null,"abstract":"This study investigates the association between parity and type 2 diabetes mellitus (T2DM) in Japanese women, considering the clinical history of gestational diabetes mellitus (GDM) and menopausal status, which are known risk factors for T2DM. Overall, 30,116 Japanese women (6,588 premenopausal and 23,528 postmenopausal) were included in this cross-sectional study. They were divided into two groups according to menopausal status (premenopausal and postmenopausal women), and the association between parity and T2DM was evaluated using a multiple logistic regression model with possible confounders, including a clinical history of GDM. The association between parity and T2DM was not statistically significant in premenopausal women. In contrast, a linear graded association between parity and T2DM was found in postmenopausal women. Furthermore, the association between parity and T2DM in postmenopausal women was attenuated after adjusting for body weight gain after the age of 20 years. A clinical history of GDM was significantly associated with a high risk for T2DM, regardless of adjustment for body weight gain after the age of 20 years in both premenopausal and postmenopausal women. Parity is associated with an increased risk of T2DM in postmenopausal women but not in premenopausal women. Maintaining appropriate body weight would be beneficial in attenuating the risk of T2DM in postmenopausal women. A clinical history of GDM is a risk factor for T2DM in both pre- and postmenopausal women; therefore, women with a clinical history of GDM require continuous medical care to survey for T2DM.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"366-381"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814038","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}

引用次数: 0

Phenome-Wide Investigation of the Causal Associations Between Pre-Pregnancy Obesity Traits and Gestational Diabetes: A Two-Sample Mendelian Randomization Analyses. 孕前肥胖特征与妊娠糖尿病之间因果关系的全局调查：双样本孟德尔随机分析。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-05-24 DOI: 10.1007/s43032-024-01577-w

Mengjin Hu, Xiaosong Li, Jiangong Wu, Boyu Li, Jinggang Xia, Yuejin Yang, Chunlin Yin

{"title":"Phenome-Wide Investigation of the Causal Associations Between Pre-Pregnancy Obesity Traits and Gestational Diabetes: A Two-Sample Mendelian Randomization Analyses.","authors":"Mengjin Hu, Xiaosong Li, Jiangong Wu, Boyu Li, Jinggang Xia, Yuejin Yang, Chunlin Yin","doi":"10.1007/s43032-024-01577-w","DOIUrl":"10.1007/s43032-024-01577-w","url":null,"abstract":"Pre-pregnancy obesity was associated with gestational diabetes in observational studies, but whether this relationship is causal remains to be determined. To evaluate whether pre-pregnancy obesity traits causally affect gestational diabetes risk, a two-sample Mendelian randomization (MR) analysis was performed utilizing summary-level statistics from published genome-wide association studies (GWAS). Obesity-related traits included body mass index (BMI), overweight, obesity, obesity class 1, obesity class 2, obesity class 3, childhood obesity, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), percent liver fat, visceral adipose tissue volume, abdominal subcutaneous adipose tissue volume. Effect estimates were evaluated using the inverse-variance weighting method. Weighted median, MR-Egger, simple mode, and weighted mode were performed as sensitivity analyses. Genetically predicted pre-pregnancy BMI [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.45-1.95; P = 9.13 × 10-12], overweight (OR = 1.49; 95% CI: 1.21-1.85; P = 2.06 × 10-4), obesity (OR = 1.25; 95% CI: 1.18-1.33; P = 8.01 × 10-13), obesity class 1 (OR = 1.31; 95% CI: 1.17-1.46; P = 1.49 × 10-6), obesity class 2 (OR = 1.26; 95% CI: 1.16-1.37; P = 5.23 × 10-8), childhood obesity (OR = 1.33; 95% CI: 1.23-1.44; P = 4.06 × 10-12), and WHR (OR = 2.35; 95% CI: 1.44-3.83; P = 5.89 × 10-4) were associated with increased risk of gestational diabetes. No significant association was observed with obesity class 3, WC, HC, percent liver fat, visceral adipose tissue volume, or abdominal subcutaneous adipose tissue volume. Similar results were observed in sensitivity analyses. Therefore, genetically predicted pre-pregnancy obesity traits may increase the risk of gestational diabetes. Weight control before pregnancy may be beneficial to prevent gestational diabetes.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"395-403"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093997","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}

引用次数: 0

Ultra-Fast Warming Procedure of Vitrified Blastocysts Results in Maintained Embryology and Clinical Outcomes. 玻璃化囊胚的超高速加热过程对维持胚胎学和临床结果的影响。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2025-01-09 DOI: 10.1007/s43032-024-01762-x

Jenna Lammers, Arnaud Reignier, Sophie Loubersac, Maxime Chaillot, Thomas Freour

{"title":"Ultra-Fast Warming Procedure of Vitrified Blastocysts Results in Maintained Embryology and Clinical Outcomes.","authors":"Jenna Lammers, Arnaud Reignier, Sophie Loubersac, Maxime Chaillot, Thomas Freour","doi":"10.1007/s43032-024-01762-x","DOIUrl":"10.1007/s43032-024-01762-x","url":null,"abstract":"Vitrification has revolutionized embryo cryopreservation, but represents a significant workload in the IVF lab. We evaluated here an ultrafast blastocyst warming procedure in order to improve workflow while maintaining clinical outcome. We first evaluated the expression of main markers of lineage specification in a subset of blastocysts donated to research warmed with ultrafast protocol. We then performed a prospective pseudo-randomized pilot study comparing blastocyst survival, reexpansion and live birth rates between standard (3 steps, 15 min), and ultrafast warming protocol (1 step, 2 min). Finally, survival, reexpansion and live birth rates (LBR) obtained with ultrafast warming protocol were prospectively collected during 3 months and compared with previous indicators. Immunofluorescence experiments showed that staining and spatial organization of cell fate markers were conserved with ultrafast protocol. Survival, reexpansion and LBR were strictly comparable between standard (n = 47 cycles) and ultrafast (n = 39 cycles) groups in the pilot study (100 vs 100%, 80 vs 76% and 29.8 vs 30.7% in standard and simplified groups respectively). Survival, expansion and LBR obtained with the ultrafast warming protocol over the next 3-month period (321 cycles, 336 embryos) were comparable with those obtained with the standard protocol throughout the 6 months (547 FBT cycles, 578 embryos) preceding shifting protocol (97.6 and 29.6% vs 97.8 and 28.3% respectively, p > 0.05 for both). In conclusion, using an ultrafast blastocyst warming procedure results in similar embryology and clinical outcomes compared with standard protocol, but significantly shortens the technical procedure, ultimately improving the overall lab's workflow.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"495-501"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954096","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}

引用次数: 0

Voltage-Gated Calcium Channels and the Parity-Dependent Differential Uterine Response to Oxytocin in Rats. 电压门控钙通道与大鼠子宫对催产素的不同反应

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI: 10.1007/s43032-024-01765-8

Korie Sondgeroth, Elisabeth Boyman, Riya Pathare, Maura Porta

{"title":"Voltage-Gated Calcium Channels and the Parity-Dependent Differential Uterine Response to Oxytocin in Rats.","authors":"Korie Sondgeroth, Elisabeth Boyman, Riya Pathare, Maura Porta","doi":"10.1007/s43032-024-01765-8","DOIUrl":"10.1007/s43032-024-01765-8","url":null,"abstract":"The experience of pregnancy affects uterine function well beyond delivery. We previously demonstrated that the response to oxytocin is more robust in the uteri of proven breeder rats. This study investigates the contribution of T-type calcium channels (TTCCs) and L-type calcium channels (LTCCs) to the distinct response of virgin (V) and proven breeder (PB) rat uteri to oxytocin. Dose-inhibition responses to mibefradil (TTCC inhibitor) and verapamil (LTCC inhibitor) were conducted on isolated V and PB uterine strips. These experiments were followed by dose-response curves to oxytocin (10-10 to 10-5 M) in the presence of 10 µM of each inhibitor. Area-under-the-curve (AUC), amplitude, frequency, and duration of contractions were measured. V uteri generally showed a greater dependence on VGCCs, especially TTCCs. However, PB uteri exhibited a stronger frequency response to oxytocin. Blocking TTCCs had a more pronounced impact on the differential oxytocin response, particularly affecting the frequency component of contractions. The stronger frequency response in PB uteri may be due to a higher concentration of TTCCs in their myometrial pacemaker cells. This study provides supporting evidence that pregnancy induces lasting changes in uterine calcium handling. Our findings suggest that TTCCs play a more important role than LTCC in the parity-dependent differential response to oxytocin. The impact of ORAI and TRP channels still needs to be evaluated, to gain a more comprehensive understanding of the relative impact of voltage-gated calcium channels vs. storage-operated calcium entry channels on this phenomenon.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"300-315"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979822","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}

引用次数: 0

Placental and Fetal Metabolic Reprogramming in Pregnancies with Intrauterine Growth Restriction. 宫内生长受限妊娠的胎盘和胎儿代谢重编程。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-12-18 DOI: 10.1007/s43032-024-01764-9

Francesca Innocenti, Rosa Teresa Scaramuzzo, Federica Lunardi, Simona Tosto, Francesca Pascarella, Maura Calvani, Alessandro Pini, Luca Filippi

{"title":"Placental and Fetal Metabolic Reprogramming in Pregnancies with Intrauterine Growth Restriction.","authors":"Francesca Innocenti, Rosa Teresa Scaramuzzo, Federica Lunardi, Simona Tosto, Francesca Pascarella, Maura Calvani, Alessandro Pini, Luca Filippi","doi":"10.1007/s43032-024-01764-9","DOIUrl":"10.1007/s43032-024-01764-9","url":null,"abstract":"The high-altitude hypoxia model demonstrates that insufficiently oxygenated placentas activate compensatory mechanisms to ensure fetal survival, hinging on the transcription factor hypoxia-inducible factor-1. The aim of the present study is to investigate whether and when similar mechanisms are also activated during intrauterine growth restriction (IUGR). A retrospective observational study evaluated a series of umbilical cord blood samples, which provide a realistic representation of the fetal intrauterine status, collected from a cohort of preterm and term neonates, both affected and not affected by IUGR. Results demonstrate that preterm IUGR fetuses receive a lower supply of oxygen and glucose from the placenta, along with a greater provision of lactate and carbon dioxide compared to non-IUGR neonates. Simultaneously, preterm IUGR fetuses increase oxygen extraction and reduce lactate production. These differences between IUGR and non-IUGR placentas and fetuses disappear as the term of pregnancy approaches. In conclusion, this study suggests that hypoperfused placentas in preterm pregnancies with IUGR activate a metabolic reprogramming aimed at favoring glycolytic metabolism to ensure fetal oxygenation, even though the availability of glucose for the fetus is reduced. Consequently, preterm IUGR fetuses activate gluconeogenetic metabolic reprogramming, despite it being energetically expensive. These metabolic adaptations disappear in the last weeks of pregnancy, likely due to physiological placental aging that increases the fetoplacental availability of oxygen. Placental oxygenation appears to be the main driver of metabolic reprogramming; however, further studies are necessary to identify the underlying biological mechanisms modulated by oxygen.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"502-513"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855137","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}

引用次数: 0

Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model. JAK抑制剂AZD1480对子宫平滑肌瘤的体内疗效评价

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 Epub Date: 2024-12-29 DOI: 10.1007/s43032-024-01775-6

Michael F Neblett, Merrick T Ducharme, Jeffrey A Meridew, Andrew J Haak, Sylvie Girard, Daniel J Tschumperlin, Elizabeth A Stewart

{"title":"Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model.","authors":"Michael F Neblett, Merrick T Ducharme, Jeffrey A Meridew, Andrew J Haak, Sylvie Girard, Daniel J Tschumperlin, Elizabeth A Stewart","doi":"10.1007/s43032-024-01775-6","DOIUrl":"10.1007/s43032-024-01775-6","url":null,"abstract":"Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells. Our objective was to evaluate the efficacy of AZD1480, a JAK 1/2 inhibitor, in treating uterine leiomyomas using a patient-derived xenograft murine model. Ovariectomized immunodeficient mice received an estrogen and progesterone pellet and were subsequently implanted with human leiomyoma tissue surgically resected from premenopausal women not on hormonal medication. Mice were divided into treatment (n = 6) and vehicle control (n = 6) groups receiving either 50 mg/kg of AZD1480 or vehicle via oral gavage for 5 days/week for 28 days. Our results demonstrate a significant AZD1480-mediated reduction in both xenograft volume (59.5% vs. 0.3%; treated vs. control, p < .0001) and weight (56.0% vs. 31.2%; p = 0.03) compared to controls. Moreover, xenografts from the treated group exhibited a significant decrease in cell density(p = 0.01). Levels of pSTAT3-positive cells (4.1% vs. 10.3%), Ki67-positive cells (4.1% vs. 6.5%), and fibrillar collagen (19.8% vs. 29.5%) declined but did not reach statistical significance, whereas AZD1480 treatment significantly reduced blood vessel formation in the xenografts (20.1 vs 45.6 per FOV; p = 0.01). These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety.","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"417-427"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910414","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}

引用次数: 0

Correction: Non Invasive Preimplantation Testing for Aneuploidies in Assisted Reproduction: A SWOT Analysis. 更正：辅助生殖中非整倍体的无创植入前检测：SWOT分析。

IF 2.6 3区医学

Reproductive Sciences Pub Date : 2025-02-01 DOI: 10.1007/s43032-024-01770-x

Elena Carrillo de Albornoz, Jose Antonio Dominguez Arroyo, Yosu Franco Iriarte, Xavier Vendrell, Verónica Martínez Vidal, María Carrera Roig

引用次数: 0