Systems Biology in Reproductive Medicine最新文献

{"title":"The vitrification system may affect preterm and cesarean delivery rates after single vitrified blastocyst transfer.","authors":"Yunhong Lin,&nbsp;Lincui Da,&nbsp;Shengrong Du,&nbsp;Qingfen Chen,&nbsp;Suzhu Chen,&nbsp;Beihong Zheng","doi":"10.1080/19396368.2021.2005717","DOIUrl":"https://doi.org/10.1080/19396368.2021.2005717","url":null,"abstract":"<p><p>The purpose of this study was to investigate the possible effects of different vitrification systems on single vitrified blastocyst transfer cycles. The clinical and birth outcomes of 412 patients who underwent single vitrified blastocyst transfer between January 2018 and June 2020 were retrospectively analyzed and compared between patients who underwent blastocyst vitrification with kit A (group A, 196 patients) and those who underwent blastocyst vitrification with kit B (group B, 216 patients). Clinical outcomes, including the clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, ectopic pregnancy rate, twin pregnancy rate, and induced labor rate due to fetal malformation, were not significantly different between the two groups (P > 0.05). The preterm delivery rate among singleton newborns (11.57% vs. 3.23%, P < 0.05) and the cesarean delivery rate were significantly higher in group B than in group A (70.25% vs. 57.26%, P < 0.05). Birth outcomes, including the male-to-female ratio, low-birth-weight rate, macrosomia rate, birth defect rate, newborn gestational age, neonatal body weight, and singleton neonatal body length, were not significantly different (P > 0.05). Our findings suggest that different vitrification systems might differentially affect birth outcomes. Such disparity could reflect differences in kit composition and/or protocol.<b>ABBREVIATIONS</b>: DMSO: dimethyl sulfoxide; ES: equilibration solution; VS: vitrification solution; BMI: body mass index; ICSI: intracytoplasmic sperm injection; OR: odds ratio; CI: confidence interval.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 2","pages":"113-120"},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39709711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the role of thiol / disulfide homeostasis in the etiology of idiopathic male infertility with a novel and automated assay.","authors":"Uygar Micoogullari,&nbsp;Mehmet Caglar Cakici,&nbsp;Furkan Umut Kilic,&nbsp;Erdem Kisa,&nbsp;Burak Ozcift,&nbsp;Alper Caglayan,&nbsp;Salim Neselioglu,&nbsp;Omer Faruk Karatas,&nbsp;Ozcan Erel","doi":"10.1080/19396368.2021.2003481","DOIUrl":"https://doi.org/10.1080/19396368.2021.2003481","url":null,"abstract":"<p><p>Idiopathic male infertility (IMI) is the absence of a reason to explain a patient's infertility, and it occurs at a frequency of %31. In this study we aimed to investigate the oxidant/antioxidant status of patients with IMI and compare their results to those of healthy controls.A total of 79 patients with IMI (group 1) and 90 healthy individuals (group 2) were included in the study. We used Erel & Neşelioğlu's thiol/disulfide homeostasis test. Collective and individual measurements of oxidative/antioxidative balance components were carried out by this novel thiol/disulfide homeostasis test. Serum antioxidant (total thiol (toSH), native thiol (SH)) and oxidant (disulfide (SS)) levels of all study participants were measured. The results from both groups were compared and analyzed statistically. After toSH, SH, and SS levels were determined, SS/toSH% and SS/SH% levels for each group were analyzed separately and compared statistically.The toSH, SH levels, and SS/SH%, SS/toSH% ratios were significantly different between the groups (p < 0.05).While antioxidant parameters (toSH and SH values) decreased in group1, oxidant parameters (SS/SH%, SS/toSH%) increased significantly. Although SS values were higher in group 1, the difference was not significant (p = 0.214). The SH cutoff value of 507.15 µmol/L predicted the probability of IMI development with 72.2% sensitivity and 74.4% specificity and toSH cutoff value of 545.45 µmol/L predicted IMI development with 70.9% sensitivity and 73.3 specificity (p < 0.001). Multivariate logistic regression analysis showed that the only independent risk factor for the development of IMI is SH. Patients with IMI had a significant change in their thiol/disulfide homeostasis, which suggests the involvement of this imbalance in the pathophysiology of IMI. Furthermore, these results also support the notion of the involvement of oxidative stress in sperm dysfunction. It also points to the possibility of using antioxidants in IMI treatment.<b>Abbreviations:</b> IMI: idiopathic male infertility; toSH: total thiol; SH: native thiol; SS: disulfide; OS: oxidative stress; ROS: reactive oxygen species; DCF: dichlorofluorescein; MiOXSYS: male infertility oxidative system; MOSI: male oxidative stress infertility; LC: L-carnitine; LAC: L-acetylcarnitine; Vit: vitamin; OAT: oligoasthenozoospermia; TMSC: total motile sperm count; WHO: World Health Organization; BMI: body mass index; DTNB: 5,5'-dithiobis-2-nitrobenzoic acid; CV: coefficient variation; ROC: receiver operating characteristic; PR: progressive, NP: non-progressive.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 2","pages":"162-168"},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators.","authors":"Jingyuan Xiong,&nbsp;Ye Tian,&nbsp;Aru Ling,&nbsp;Zhenmi Liu,&nbsp;Li Zhao,&nbsp;Guo Cheng","doi":"10.1080/19396368.2021.2003910","DOIUrl":"https://doi.org/10.1080/19396368.2021.2003910","url":null,"abstract":"<p><p>Epidemiological studies have shown that genistein, an isoflavonoid phytoestrogen from soybean, affects endocrine and reproductive systems and alters pubertal onset. Administration of genistein in mice could impact the electrophysiology of hypothalamic neurons associated with the secretion of gonadotropin-releasing hormone (GnRH), a key component of hypothalamic-pituitary-gonadal (HPG) axis that governs hormone release and reproductive maturation. However, whether genistein could directly influence GnRH secretion in GnRH-specific neurons requires further investigation. Here, mouse hypothalamic GT1-7 neurons were recruited as a GnRH-expressing model to directly evaluate the effect and mechanisms of genistein on GnRH release. Results from this study demonstrated that genistein treatment decreased cell viability, impacted cell cycle distribution, and induced apoptosis of GT1-7 cells. A high concentration of genistein (20 μM) significantly increased GnRH secretion by 122.4% compared to the control. Since GnRH release is regulated by components of the kisspeptin-neurokinin-dynorphin (KNDy) system and regulators including SIRT1, PKC_γ, and MKRN3, their transcription and translation were examined. Significant increases were observed for the mRNA and protein levels of the KNDy component kisspeptin receptor (<i>Gpr54</i>/Kissr). Compared to the control, genistein treatment upregulated the level of <i>Sirt1</i> mRNA level, while it downregulated <i>Prkcg</i> and <i>Mkrn3</i> expression. Therefore, this study provided direct evidence that genistein treatment could affect GnRH secretion by modulating kisspeptin receptors, SIRT1, PKC_γ and MKRN3 in GT1-7 cells.<b>Abbreviations:</b> GnRH: gonadotropin-releasing hormone; HPG: hypothalamic-pituitary-gonadal; KNDy: kisspeptin-neurokinin-dynorphin; LH: luteinizing hormone; FSH: follicle-stimulating hormone; ARC: arcuate nucleus; ER: estrogen receptor; SIRT1: silent information regulator 1; PKCγ: protein kinase c γ: MKRN3: makorin ring finger protein 3; LC: lethal concentration; PI: propidium iodide; ECL: chemiluminescence; BCA: bicinchoninic acid assay; PBS: phosphate-buffered saline; CT: fluorescence reached threshold; PVDF: polyvinylidene difluoride.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 2","pages":"138-150"},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39787034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSHR antagonists can trigger a PCOS-like state.","authors":"Faiza Hanif Waghu,&nbsp;Karishma Desai,&nbsp;Sumana Srinivasan,&nbsp;Kaushiki S Prabhudesai,&nbsp;Vikas Dighe,&nbsp;Kareenhalli V Venkatesh,&nbsp;Susan Idicula-Thomas","doi":"10.1080/19396368.2021.2010837","DOIUrl":"https://doi.org/10.1080/19396368.2021.2010837","url":null,"abstract":"<p><p>Over the recent years, FSHR has become an important target for development of fertility regulating agents, as impairment of FSH-FSHR interaction can lead to subfertility or infertility. In our previous study, we identified a 9-mer peptide (FSHβ (89-97)) that exhibited FSHR antagonist activity. The histopathological and biochemical observations indicated, in addition to FSHR antagonism, a striking resemblance to a PCOS-like state. These observations led us to hypothesize that use of FSHR antagonists can trigger a PCOS-like state. In the present study, to validate this hypothesis, we performed qRT-PCR validation using ovarian tissue samples from our previous study. Expression of three genes known to be differentially expressed in PCOS was evaluated and found to be similar to the PCOS state. To further test the hypothesis, theoretical simulations were carried out by using the human menstrual cycle model available in the literature. Model simulations for FSHR antagonism were indicative of increased testosterone levels, increased ratio of luteinizing hormone/follicle stimulating hormone, and stockpiling of secondary follicles, which are typical characteristics of PCOS. The findings of this study will be relevant while reviewing the utility of FSHR antagonists for fertility regulation and reproductive medicine.<b>Abbreviations:</b> FSH: Follicle-stimulating hormone; FSHR: Follicle-stimulating hormone receptor; cAMP: Cyclic adenosine 3'5' monophosphate; PKA: Protein kinase A; PI3K: Phosphoinositide 3-kinase; PKB: protein kinase B; ERK1/2: Extracellular signal-regulated protein kinase 1/2; MAPK: Mitogen-activated protein kinases; T: testosterone; E2: estradiol; PCOS: Polycystic ovarian syndrome; LH: luteinizing hormone; Lhcgr: luteinizing hormone/choriogonadotropin receptor; CYP17A1: cytochrome P450 family 17 subfamily A member 1; Inhba: inhibin subunit beta A; qRT-PCR: Real-Time quantitative reverse transcription polymerase chain reaction; FSHβ: Follicle-stimulating hormone β subunit; Ct: Cycle threshold; Rn18s: Rattus norvegicus 18S ribosomal RNA.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 2","pages":"129-137"},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39772912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis.","authors":"Jing Zhang,&nbsp;Lihui Wang,&nbsp;Chunyan Li,&nbsp;Hui Zhang,&nbsp;Rui Li,&nbsp;Mingjiang Li","doi":"10.1080/19396368.2021.2013577","DOIUrl":"https://doi.org/10.1080/19396368.2021.2013577","url":null,"abstract":"<p><p>Endometriosis is a common estrogen-dependent chronic inflammatory disease that leads to infertility in women of reproductive age. Perhaps infertility reflects the reduced expression of integrin αvβ3 and HOXA10 in endometriosis. Previous studies have shown that administration of letrozole, a non-steroidal aromatase inhibitor for cancer treatment, increased the clinical pregnancy rate in women with endometriosis, but the mechanisms remain to be determined. In this communication, a rat model of endometriosis was established. Animals were treated with letrozole at 2ug/kg of body weight, intragastric administration for 15 consecutive days. Letrozole increased the expression of αvβ3 and HOXA10 in the endometriosis model and endometrial receptivity.<b>Abbreviations:</b> WOI: window of implantation; RGD: Arg-Gly-Asp; HOX: homeobox; E2: estradiol; SPF: specific pathogen-free.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 2","pages":"121-128"},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39630380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin 9 regulates Leydig cell steroidogenesis in diabetes","authors":"Arun K. Kannan, Lezy Flora Mariajoseph-Antony, Antojenifer Panneerselvam, Chithra Loganathan, Diwakar Kiduva Jothiraman, K. Anbarasu, C. Prahalathan","doi":"10.1080/19396368.2022.2033350","DOIUrl":"https://doi.org/10.1080/19396368.2022.2033350","url":null,"abstract":"Abstract Diabetes mellitus induced hyperglycemia increases oxidative stress, which contributes to impairment of male reproductive function. Aquaporins (AQPs) belong to a transmembrane protein superfamily containing 13 isoforms (AQP0-12), differentially expressed in various organs, and play a pivotal role in male reproductive function. In the current study, we investigated the relationship between AQPs and testicular steroidogenesis under hyperglycemia in vivo and in vitro. The effect of high glucose on the role of AQPs in Leydig cell steroidogenesis was analyzed in diabetic rats (in-vivo) and LC540 rat Leydig cells (in vitro) via enzyme assays, quantitative RT-PCR, siRNA knock down and western blotting. AQP 9 was significantly up-regulated in STZ-induced diabetic rat testis and high glucose treated LC540 cells. Further, oxidative stress marker nuclear factor erythroid 2-related factor 2 (Nrf2) expression was decreased with impaired testicular steroidogenesis under hyperglycemia. Knock-down of AQP 9 resulted in increased Nrf2 expression and thus increased testicular steroidogenesis in hyperglycemia. Diabetes-associated hyperglycemia induced oxidative stress is a widely proven cause for diabetes-related male infertility. Our results collectively suggest that AQP 9 impairs testicular steroidogenesis via the regulation of oxidative stress in diabetes.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 1","pages":"213 - 226"},"PeriodicalIF":2.4,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42145243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial/ethnic disparities in infertility treatment utilization in the US, 2011–2019","authors":"Deepa Dongarwar, Vicki Mercado-Evans, Sylvia Adu-Gyamfi, Mei-Li Laracuente, H. Salihu","doi":"10.1080/19396368.2022.2038718","DOIUrl":"https://doi.org/10.1080/19396368.2022.2038718","url":null,"abstract":"Abstract With delayed child-bearing age, there has been an increase in infertility rates globally and in the United States (US). Unsurprisingly, there has been a concomitant substantial increase in the number of individuals seeking infertility treatments over the last decade. This study aimed to examine the relationship between race/ethnicity and the utilization of different infertility treatments over the previous decade. We conducted this retrospective cohort study using the United States (US) Birth data files 2011–2019. We calculated the rates of infertility treatment and its subtypes over the study period. Descriptive statistics were utilized to examine the sociodemographic and birth characteristics for overall births and those associated with any infertility treatment and each of its subtypes. We calculated the level of association between race/ethnicity and utilization of infertility treatment and the subtypes using adjusted logistic regression models. We found that the rate of infertility treatments for all subtypes considered, had steadily increased by 63.7% within the past decade. In contrast, fertility enhancing drugs or Intrauterine Insemination (IUI) increased by 134%, and in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT) treatments increased by 40% over the 9-year study period. Non-Hispanic (NH) Asian women had the highest rate of any infertility treatment with a rate of 25 per 1000 births whereas Hispanic women had the lowest rate of any infertility treatment at 5.8 per 1000 births. When compared with NH-White women, NH-Asian women had a modest 7% lower likelihood (OR = 0.93, 95% CI = 0.92–0.94) of receiving any infertility treatment while NH-Black and Hispanic women had about 70% lower likelihood of receiving any infertility treatment. Our report of increased assisted reproductive technology (ART) utilization rates, and marked racial/ethnic differences in ART utilization highlight the importance of expanding knowledge of inequities that continue to impact marginalized groups, a critical step for informing actionable strategy formulations (i.e., advocacy, policy change, patient education, provider training) to address these inequities.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 1","pages":"180 - 189"},"PeriodicalIF":2.4,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45704445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of STUB1 expression and its biological significance in mouse Sertoli cells","authors":"Tao Li, Chao Zheng, W. Han, Zhen-Zhen Chen","doi":"10.1080/19396368.2022.2027554","DOIUrl":"https://doi.org/10.1080/19396368.2022.2027554","url":null,"abstract":"Abstract STIP1 Homology and U-Box Containing Protein 1 (STUB1), a ubiquitin E3 ligase initially involved in immune responses, has recently emerged as a pleiotropic regulator of different biological systems, including skeletal and male reproduction systems. On the latter, a homozygous mutation in the STUB1 gene has been identified in patients with hypogonadism. However, the pattern of expression and biological actions of STUB1 in testis remains so far unexplored. Herein, we report analyses on the testicular expression of STUB1 in human testes with impaired spermatogenesis and paracrine regulation of STUB1 expression in mouse testis development and the direct effects of ablation STUB1 on Sertoli cell (SC) functions. STUB1 was expressed abundantly in pachytene spermatocytes and SCs, and weakly in spermatogonia and differentiating spermatids in normal human testis. In contrast, Sertoli-specific expression of STUB1 was significantly decreased in the human testes with impaired spermatogenesis. Throughout postnatal development of mouse testis, however, STUB1 was expressed exclusively in the nuclei of the functionally mature SCs. The adjacent germ cell (GC)-derived IL-1α overtly regulated STUB1 expression through promoting the ETS domain transcription factor Elk-1 (ELK1)-mediated transactivation. Importantly, ablation of endogenous STUB1 caused lipid accumulation and senescence in GC co-incubated SCs. Together with previous reports on the stimulatory effects of IL-1α on cell senescence, our findings suggest that STUB1 may serve as an important negative feedback signaling to modulate the magnitude of GCs-derived IL-1α, which is normally maintained at low levels within testis.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 1","pages":"298 - 313"},"PeriodicalIF":2.4,"publicationDate":"2022-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47400570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there a role for small molecule metabolite biomarkers in the development of a diagnostic test for endometriosis?","authors":"Nicola E Tomkins, J. Girling, B. Boughton, S. Holdsworth-Carson","doi":"10.1080/19396368.2022.2027045","DOIUrl":"https://doi.org/10.1080/19396368.2022.2027045","url":null,"abstract":"Abstract Endometriosis is a disease defined by the presence of benign lesions of endometrial-like glands and stroma outside the endometrial cavity. Affecting an estimated 11.4% of Australian women, symptoms include chronic pelvic pain, dysmenorrhea and infertility. The current gold standard of diagnosis requires an expensive and invasive laparoscopic surgery, resulting in delayed time to treatment. The identification of a non-invasive endometriosis biomarker – a measurable factor correlating with disease presence or activity – has therefore become a priority in endometriosis research, although no biomarker has yet been validated. As small molecule metabolites and lipids have emerged as a potential focus, this review with systematic approach, aims to summarize studies examining metabolomic biomarkers of endometriosis in order to guide future research. EMBASE, PubMed and Web of Science were searched using keywords: lipidomics OR metabolomics OR metabolome AND diagnostic tests OR biomarkers AND endometriosis, and only studies written in English from August 2000 to August 2020 were included. Twenty-nine studies met inclusion and exclusion criteria and were included. These studies identified potential biomarkers in serum, ectopic tissue, eutopic endometrium, peritoneal fluid, follicular fluid, urine, cervical swabs and endometrial fluid. Glycerophospholipids were identified as potential biomarkers in all specimens, except urine and cervical swab specimens. However, no individual molecule or metabolite combination has reached clinical diagnostic utility. Further research using large study populations with robust patient phenotype and specimen characterisation is required if we are to make progress in identifying and validating a non-invasive diagnostic test for endometriosis.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 1","pages":"89 - 112"},"PeriodicalIF":2.4,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42170794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity.","authors":"Sharon Anderson,&nbsp;Peining Xu,&nbsp;Alexander J Frey,&nbsp;Jason R Goodspeed,&nbsp;Mary T Doan,&nbsp;John J Orris,&nbsp;Nicolle Clements,&nbsp;Michael J Glassner,&nbsp;Nathaniel W Snyder","doi":"10.1080/19396368.2021.2003479","DOIUrl":"https://doi.org/10.1080/19396368.2021.2003479","url":null,"abstract":"<p><p>Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure then, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from ¹³C-labeled substrates resulting in an M + 2 isotopologue that contains 2 ¹³C atoms. Comparing the fate of three major carbon sources, mean enrichment of M + 2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p = 0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M + 2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: -6.02, CI: -1.74,-13.79, p = 0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.<b>Abbreviations:</b> CCs: cumulus cells; COC: cumulus-oocyte complex; LC-MS: liquid chromatography-mass spectrometry; acetyl-CoA: acetyl-Coenzyme A; CoA: Coenzyme A.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"68 1","pages":"36-43"},"PeriodicalIF":2.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821170/pdf/nihms-1766969.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}