Reproductive biology and endocrinology : RB&E最新文献

{"title":"Proteomic analysis of extracellular vesicles secreted by primary human epithelial endometrial cells reveals key proteins related to embryo implantation.","authors":"Marina Segura-Benítez,&nbsp;María Cristina Carbajo-García,&nbsp;Ana Corachán,&nbsp;Amparo Faus,&nbsp;Antonio Pellicer,&nbsp;Hortensia Ferrero","doi":"10.1186/s12958-021-00879-x","DOIUrl":"https://doi.org/10.1186/s12958-021-00879-x","url":null,"abstract":"<p><strong>Background: </strong>Successful implantation is dependent on coordination between maternal endometrium and embryo, and the role of EVs in the required cross-talk cell-to-cell has been recently established. In this regard, it has been reported that EVs secreted by the maternal endometrium can be internalized by human trophoblastic cells transferring their contents and enhancing their adhesive and invasive capacity. This is the first study to comprehensively evaluate three EV isolation methods on human endometrial epithelial cells in culture and to describe the proteomic content of EVs secreted by pHEECs from fertile women.</p><p><strong>Methods: </strong>Ishikawa cells and pHEECs were in vitro cultured and hormonally treated; subsequently, conditioned medium was collected and EVs isolated. Ishikawa cells were used for the comparison of EVs isolation methods ultracentrifugation, ExoQuick-TC and Norgen Cell Culture Media Exosome Purification Kit (n = 3 replicates/isolation method). pHEECs were isolated from endometrial biopsies (n = 8/replicate; 3 replicates) collected from healthy oocyte donors with confirmed fertility, and protein content of EVs isolated by the most efficient methodology was analysed using liquid chromatography-tandem mass spectrometry. EV concentration and size were analyzed by nanoparticle tracking analysis, EV morphology visualized by transmission electron microscopy and protein marker expression was determined by Western blotting.</p><p><strong>Results: </strong>Ultracentrifugation was the most efficient methodology for EV isolation from medium of endometrial epithelial cells. EVs secreted by pHEECs and isolated by ultracentrifugation were heterogeneous in size and expressed EV protein markers HSP70, TSG101, CD9, and CD81. Proteomic analysis identified 218 proteins contained in these EVs enriched in biological processes involved in embryo implantation, including cell adhesion, differentiation, communication, migration, extracellular matrix organization, vasculature development, and reproductive processes. From these proteins, 82 were selected based on their functional relevance in implantation success as possible implantation biomarkers.</p><p><strong>Conclusions: </strong>EV protein cargos are implicated in biological processes related to endometrial receptivity, embryo implantation, and early embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs. Identified proteins may define new biomarkers of endometrial receptivity and implantation success.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"3"},"PeriodicalIF":4.4,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated SAA1 promotes the development of insulin resistance in ovarian granulosa cells in polycystic ovary syndrome.","authors":"Qinling Zhu,&nbsp;Yue Yao,&nbsp;Lizhen Xu,&nbsp;Hasiximuke Wu,&nbsp;Wangsheng Wang,&nbsp;Yaqiong He,&nbsp;Yuan Wang,&nbsp;Yao Lu,&nbsp;Jia Qi,&nbsp;Ying Ding,&nbsp;Xinyu Li,&nbsp;Jiaan Huang,&nbsp;Hanting Zhao,&nbsp;Yanzhi Du,&nbsp;Kang Sun,&nbsp;Yun Sun","doi":"10.1186/s12958-021-00873-3","DOIUrl":"https://doi.org/10.1186/s12958-021-00873-3","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive.</p><p><strong>Methods: </strong>Follicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells.</p><p><strong>Results: </strong>Ovarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB).</p><p><strong>Conclusions: </strong>Human granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"4"},"PeriodicalIF":4.4,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homozygous mutation in SLO3 leads to severe asthenoteratozoospermia due to acrosome hypoplasia and mitochondrial sheath malformations.","authors":"Mingrong Lv,&nbsp;Chunyu Liu,&nbsp;Chunjie Ma,&nbsp;Hui Yu,&nbsp;Zhongmei Shao,&nbsp;Yang Gao,&nbsp;Yiyuan Liu,&nbsp;Huan Wu,&nbsp;Dongdong Tang,&nbsp;Qing Tan,&nbsp;Junqiang Zhang,&nbsp;Kuokuo Li,&nbsp;Chuan Xu,&nbsp;Hao Geng,&nbsp;Jingjing Zhang,&nbsp;Hang Li,&nbsp;Xiaohong Mao,&nbsp;Lei Ge,&nbsp;Feifei Fu,&nbsp;Kaixin Zhong,&nbsp;Yuping Xu,&nbsp;Fangbiao Tao,&nbsp;Ping Zhou,&nbsp;Zhaolian Wei,&nbsp;Xiaojin He,&nbsp;Feng Zhang,&nbsp;Yunxia Cao","doi":"10.1186/s12958-021-00880-4","DOIUrl":"https://doi.org/10.1186/s12958-021-00880-4","url":null,"abstract":"<p><strong>Background: </strong>Potassium channels are important for the structure and function of the spermatozoa. As a potassium transporter, the mSlo3 is essential for male fertility as Slo3 knockout male mice were infertile with the series of functional defects in sperm cells. However, no pathogenic variant has been detected in human SLO3 to date. Here we reported a human case with homozygous SLO3 mutation. The function of SLO3 in human sperm and the corresponding assisted reproductive strategy are also investigated.</p><p><strong>Methods: </strong>We performed whole-exome sequencing analysis from a large cohort of 105 patients with asthenoteratozoospermia. The effects of the variant were investigated by quantitative RT-PCR, western blotting, and immunofluorescence assays using the patient spermatozoa. Sperm morphological and ultrastructural studies were conducted using haematoxylin and eosin staining, scanning and transmission electron microscopy.</p><p><strong>Results: </strong>We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility. This SLO3 variant was rare in human control populations and predicted to be deleterious by multiple bioinformatic tools. Sperm from the individual harbouring the homozygous SLO3 variant exhibited severe morphological abnormalities, such as acrosome hypoplasia, disruption of the mitochondrial sheath, coiled tails, and motility defects. The levels of SLO3 mRNA and protein in spermatozoa from the affected individual were reduced. Furthermore, the acrosome reaction, mitochondrial membrane potential, and membrane potential during capacitation were also afflicted. The levels of acrosome marker glycoproteins and PLCζ1 as well as the mitochondrial sheath protein HSP60 and SLO3 auxiliary subunit LRRC52, were significantly reduced in the spermatozoa from the affected individual. The affected man was sterile due to acrosome and mitochondrial dysfunction; however, intra-cytoplasmic sperm injection successfully rescued this infertile condition.</p><p><strong>Conclusions: </strong>SLO3 deficiency seriously impact acrosome formation, mitochondrial sheath assembly, and the function of K⁺ channels. Our findings provided clinical implications for the genetic and reproductive counselling of affected families.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"5"},"PeriodicalIF":4.4,"publicationDate":"2022-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inhibitory effect of AMP-activated protein kinase (AMPK) on chemokine and prostaglandin production in human endometrial stromal cells.","authors":"Yasushi Kawano,&nbsp;Hatsumi Sato,&nbsp;Kaori Goto,&nbsp;Masakazu Nishida,&nbsp;Kaei Nasu","doi":"10.1186/s12958-021-00867-1","DOIUrl":"https://doi.org/10.1186/s12958-021-00867-1","url":null,"abstract":"<p><strong>Background: </strong>To investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1β in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR).</p><p><strong>Methods: </strong>Endometrial specimens were obtained and cultured. We examined the effects of IL-1β, IL-1 ra and AICAR on the production of IL-8, MCP-1, PGE2 and PGF2α in human ESCs. The phosphorylations of AMPK, IκB, 4EBP-1, p70S6K and S6 ribosomal protein were analyzed by Western immunoblotting.</p><p><strong>Results: </strong>Following stimulation by IL-1β, the production of IL-8, MCP-1, PGE2 and PGF2α showed significant increases, and these increases were suppressed by AICAR. The expression of cyclooxygenase-2 (COX-2) induced by IL-1β and suppressed by AICAR. The phosphorylation of IκB, 4EBP-1, p70S6K and S6 ribosomal protein were inhibited via an AMPK-dependent signal transduction.</p><p><strong>Conclusions: </strong>The production of IL-8, MCP-1, PGE2 and PGF2α induced by IL-1β in ESCs were involved in the negative regulatory mechanisms of AMPK. The substances that activate AMPK may be promising agents for the treatment of pathological problems such as dysmenorrhea.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"188"},"PeriodicalIF":4.4,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39744063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.","authors":"Jianguo Chen,&nbsp;Chaoran Huang,&nbsp;Tongtong Zhang,&nbsp;Wuqing Gong,&nbsp;Xiaofeng Deng,&nbsp;Hua Liu,&nbsp;Jinbo Liu,&nbsp;Yuanbiao Guo","doi":"10.1186/s12958-021-00863-5","DOIUrl":"https://doi.org/10.1186/s12958-021-00863-5","url":null,"abstract":"<p><p>Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, - 0.76-- 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, - 0.97-- 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, - 1.13-- 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, - 1.49-- 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"189"},"PeriodicalIF":4.4,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39619910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased METTL3-mediated m⁶A methylation inhibits embryo implantation by repressing HOXA10 expression in recurrent implantation failure.","authors":"Pingping Xue,&nbsp;Wenbo Zhou,&nbsp;Wenqiang Fan,&nbsp;Jianya Jiang,&nbsp;Chengcai Kong,&nbsp;Wei Zhou,&nbsp;Jianmei Zhou,&nbsp;Xiaoyang Huang,&nbsp;Haiyan Yang,&nbsp;Qian Han,&nbsp;Bin Zhang,&nbsp;Lingyun Xu,&nbsp;Bin Yu,&nbsp;Li Chen","doi":"10.1186/s12958-021-00872-4","DOIUrl":"https://doi.org/10.1186/s12958-021-00872-4","url":null,"abstract":"<p><strong>Background: </strong>Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N⁶-methyladenosine (m⁶A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied.</p><p><strong>Methods: </strong>Global m⁶A levels and major m⁶A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m⁶A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m⁶A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay.</p><p><strong>Results: </strong>Global m⁶A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased β3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m⁶A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro.</p><p><strong>Conclusion: </strong>Increased METTL3-mediated m⁶A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"187"},"PeriodicalIF":4.4,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39813665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the value of progesterone and progesterone/estradiol ratio on the hCG trigger day in predicting pregnancy outcomes of PCOS patients undergoing IVF/ICSI: a retrospective cohort study.","authors":"Yiqing Yang,&nbsp;Bowen Liu,&nbsp;Gengxiang Wu,&nbsp;Jing Yang","doi":"10.1186/s12958-021-00862-6","DOIUrl":"https://doi.org/10.1186/s12958-021-00862-6","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy.</p><p><strong>Methods: </strong>The clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome.</p><p><strong>Results: </strong>The number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001) was greater in the high progesterone group (progesterone ≥ 0.92 ng/mL). In the high P/E2 group(P/E2 ratio ≥ 0.3), the number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001), as well as the rate of high-quality embryos (P = 0.040) were significantly decreased. In ultralong GnRH agonist protocol, the implantation rate(P < 0.001), hCG positive rate (P < 0.001), clinical pregnancy rate (P < 0.001) and live birth rate (P < 0.001) were all significantly higher than long GnRH agonist protocol and GnRH antagonist protocol. The clinical pregnancy rate of high progesterone group was significantly lower than that of low progesterone group in ultralong GnRH agonist (P = 0.008). The progesterone level could be used as an indicator to predict the positive clinical pregnancy (long GnRH agonist: P = 0.001; ultralong GnRH agonist: P < 0.001) except in cycles using GnRH antagonist (P = 0.169). In the ultralong GnRH agonist, the value of progesterone level in the prediction of clinical pregnancy was significantly higher than that of the P/E2 ratio (P = 0.021).</p><p><strong>Conclusions: </strong>In PCOS patients, the progesterone level is associated with clinical pregnancy rate while P/E2 ratio is not. In subgroup analysis using three different COS protocols, a significant association between progesterone level and clinical pregnancy rate can be observed in the long GnRH agonist protocol and ultralong GnRH agonist protocol. The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong GnRH agonist cycles.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"184"},"PeriodicalIF":4.4,"publicationDate":"2021-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of maturation dynamics and developmental competence of in vitro matured oocytes under time-lapse monitoring.","authors":"Qiyu Yang,&nbsp;Lixia Zhu,&nbsp;Meng Wang,&nbsp;Bo Huang,&nbsp;Zhou Li,&nbsp;Juan Hu,&nbsp;Qingsong Xi,&nbsp;Jing Liu,&nbsp;Lei Jin","doi":"10.1186/s12958-021-00868-0","DOIUrl":"https://doi.org/10.1186/s12958-021-00868-0","url":null,"abstract":"<p><strong>Background: </strong>To improve the developmental competence of in vitro cultured oocytes, extensive literature focused on maturation rate improvement with different additives in culture medium, while studies investigating the maturation dynamics of oocytes during in vitro maturation (IVM) and the influencing factors on oocyte viability are scarce.</p><p><strong>Methods: </strong>The study involved a retrospective observation by time-lapse monitoring of the IVM process of 157 donated GV oocytes from 59 infertile couples receiving ICSI in 2019, in Tongji Hospital, Wuhan, China. The GV oocytes derived from controlled ovarian hyperstimulation (COH) cycles underwent rescue IVM (R-IVM), and the maturation dynamics, including GVBD time (GV-MI), time from GVBD to maturation (MI-MII), maturation time (GV-MII), and MII arrest duration (MII-ICSI), were recorded by time-lapse monitoring. The matured oocytes were inseminated at different MII arrest points and subsequent embryo developments were assessed. The effects of baseline clinical characteristics, oocyte diameters, and maturation dynamics on the developmental competence of the oocytes were also analyzed.</p><p><strong>Results: </strong>Totally, 157 GV oocytes were collected. GVBD happened in 111 oocytes, with a median GV-MI duration of 3.7 h. The median MI-MII duration was 15.6 h and the median GV-MII duration was 19.5 h. The maturation rate reached 56.7% at 24 h and 66.9% at 48 h, and the clinical factors, including patient age, FSH level, AMH level, ovarian stimulation protocol, and serum estradiol and progesterone levels on hCG trigger day, showed no effects on the 24-h maturation rate. The normal fertilization rate of oocytes resuming meiosis within 8 h and matured within 24 h was significantly higher than that of oocytes resuming meiosis after 8 h and matured after 24 h. Furthermore, among those oocytes matured within 24 h, the high-quality embryo formation rate of oocytes resuming meiosis within 4.5 h and matured within 19 h was significantly higher. All stated time was measured from the start point of IVM. Additionally, for oocytes from patients with serum progesterone levels less than 1 ng/ml on hCG trigger day, the high-quality embryo formation rate was significantly increased.</p><p><strong>Conclusion: </strong>R-IVM technology could increase the available embryos for patients in routine COH cycles, but excessive culture beyond 24 h is not recommended. GV-MI duration of the oocyte, recorded by time-lapse system, and serum progesterone levels of patients on hCG trigger day can significantly affect the developmental potential of the IVM oocytes.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"183"},"PeriodicalIF":4.4,"publicationDate":"2021-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pak2 reduction induces a failure of early embryonic development in mice.","authors":"Juan Zeng,&nbsp;Nengqing Liu,&nbsp;Yinghong Yang,&nbsp;Yi Cheng,&nbsp;Yuanshuai Li,&nbsp;Xiaoxia Guo,&nbsp;Qian Luo,&nbsp;Lifen Zhu,&nbsp;Hongmei Guan,&nbsp;Bing Song,&nbsp;Xiaofang Sun","doi":"10.1186/s12958-021-00865-3","DOIUrl":"https://doi.org/10.1186/s12958-021-00865-3","url":null,"abstract":"<p><strong>Background: </strong>The quality of the early embryo is vital to embryonic development and implantation. As a highly conserved serine/threonine kinase, p21-activated kinase 2 (Pak2) participates in diverse biologic processes, especially in cytoskeleton remodeling and cell apoptosis. In mice, Pak2 knock out and endothelial depletion of Pak2 showed embryonic lethality. However, the role of Pak2 in preimplantation embryos remains unelucidated.</p><p><strong>Methods: </strong>In the present work, Pak2 was reduced using a specific small interfering RNA in early mouse embryos, validating the unique roles of Pak2 in spindle assembly and DNA repair during mice early embryonic development. We also employed immunoblotting, immunostaining, in vitro fertilization (IVF) and image quantification analyses to test the Pak2 knockdown on the embryonic development progression, spindle assembly, chromosome alignment, oxidative stress, DNA lesions and blastocyst cell apoptosis. Areas in chromatin with γH2AX were detected by immunofluorescence microscopy and serve as a biomarker of DNA damages.</p><p><strong>Results: </strong>We found that Pak2 knockdown significantly reduced blastocyst formation of early embryos. In addition, Pak2 reduction led to dramatically increased abnormal spindle assembly and chromosomal aberrations in the embryos. We noted the overproduction of reactive oxygen species (ROS) with Pak2 knockdown in embryos. In response to DNA double strand breaks (DSBs), the histone protein H2AX is specifically phosphorylated at serine139 to generate γH2AX, which is used to quantitative DSBs. In this research, Pak2 knockdown also resulted in the accumulation of phosphorylated γH2AX, indicative of increased embryonic DNA damage. Commensurate with this, a significantly augmented rate of blastocyst cell apoptosis was detected in Pak2-KD embryos compared to their controls.</p><p><strong>Conclusions: </strong>Collectively, our data suggest that Pak2 may serve as an important regulator of spindle assembly and DNA repair, and thus participate in the development of early mouse embryos.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"181"},"PeriodicalIF":4.4,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39580689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant follicular stimulating hormone plus recombinant luteinizing hormone versus human menopausal gonadotropins- does the source of LH bioactivity affect ovarian stimulation outcome?","authors":"M Kirshenbaum,&nbsp;O Gil,&nbsp;J Haas,&nbsp;R Nahum,&nbsp;E Zilberberg,&nbsp;O Lebovitz,&nbsp;R Orvieto","doi":"10.1186/s12958-021-00853-7","DOIUrl":"https://doi.org/10.1186/s12958-021-00853-7","url":null,"abstract":"<p><strong>Objective: </strong>Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common receptor, they are used interchangeably during ovarian stimulation (OS). This study aims to assess if the source of LH used during OS affects IVF outcome.</p><p><strong>Patients and methods: </strong>This was a cross sectional study of patients who underwent two consecutive IVF cycles, one included recombinant follicular stimulating hormone (FSH) plus recombinant LH [rFSH+rLH, (Pergoveris)] and the other included urinary hCG [highly purified hMG (HP-hMG), (Menopur)]. The OS protocol, except of the LH preparation, was identical in the two IVF cycles.</p><p><strong>Results: </strong>The rate of mature oocytes was not different between the treatment cycles (0.9 in the rFSH+rLH vs 0.8 in the HP-hMG, p = 0.07). Nonetheless, the mean number of mature oocytes retrieved in the rFSH+rLH treatment cycles was higher compared to the HP-hMG treatment cycles (10 ± 5.8 vs 8.3 ± 4.6, respectively, P = 0.01). Likewise, the mean number of fertilized oocytes was higher in the rFSH+rLH cycles compared with the HP-hMG cycles (8.5 ± 5.9 vs 6.4 ± 3.6, respectively, p = 0.05). There was no difference between the treatment cycles regarding the number of top-quality embryos, the ratio of top-quality embryos per number of oocytes retrieved or fertilized oocytes or the pregnancy rate.</p><p><strong>Conclusion: </strong>The differences in treatment outcome, derived by different LH preparations reflect the distinct physiological role of these molecules. Our findings may assist in tailoring a specific gonadotropin regimen when assembling an OS protocol.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"182"},"PeriodicalIF":4.4,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39571975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}