Biology of Reproduction最新文献_第10页

Improved low-invasive mRNA electroporation method into immature mouse oocytes visualizes protein dynamics during development†. 改进的低侵入性 mRNA 电穿孔法进入未成熟小鼠卵母细胞，使发育过程中的蛋白质动态可视化。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-10-14 DOI: 10.1093/biolre/ioae116

Yuhkoh Satouh, Emiko Suzuki, Keisuke Sasaki, Ken Sato

{"title":"Improved low-invasive mRNA electroporation method into immature mouse oocytes visualizes protein dynamics during development†.","authors":"Yuhkoh Satouh, Emiko Suzuki, Keisuke Sasaki, Ken Sato","doi":"10.1093/biolre/ioae116","DOIUrl":"10.1093/biolre/ioae116","url":null,"abstract":"One of the major causes of oocyte quality deterioration, chromosome segregation abnormalities manifest mainly during meiosis I, which occurs before and during ovulation. However, currently, there is a technical limitation in the introduction of mRNA into premature oocytes without impairing embryonic developmental ability. In this study, we established a low-invasive electroporation (EP) method to introduce mRNA into pre-ovulatory, germinal vesicle (GV) mouse oocytes in an easier manner than the traditional microinjection method. The EP method with an optimized impedance value resulted in the efficient introduction of mRNAs encoding enhanced green fluorescent protein (EGFP) into the GV oocytes surrounded by cumulus cells at a survival rate of 95.0%. Furthermore, the introduction of histone H2B-EGFP mRNA into the GV oocytes labeled most of the oocytes without affecting the blastocyst development rate, indicating the feasibility of the visualization of oocyte chromosomal dynamics that enable us to assay chromosomal integrity in oocyte maturation and cell count in embryonic development. The establishment of this EP method offers extensive assays to select pre-implantation embryos and enables the surveying of essential factors for mammalian oocyte quality determination.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"931-941"},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCDC189 depletion leads to oligo-astheno-teratozoospermia and male infertility in mice†. 消耗 CCDC189 会导致小鼠出现少精症和雄性不育。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-10-14 DOI: 10.1093/biolre/ioae112

Huiping Zhou, Fan Yang, Guanghua Li, Lu Yuan, Tingting Ge, Changmin Niu, Ying Zheng

{"title":"CCDC189 depletion leads to oligo-astheno-teratozoospermia and male infertility in mice†.","authors":"Huiping Zhou, Fan Yang, Guanghua Li, Lu Yuan, Tingting Ge, Changmin Niu, Ying Zheng","doi":"10.1093/biolre/ioae112","DOIUrl":"10.1093/biolre/ioae112","url":null,"abstract":"In male reproductive system, proteins containing the coiled-coil domain (CCDC) are predominantly expressed in specific regions including the testis, epididymis, seminal vesicle, and prostate. They play a vital role in centriole formation, sperm motility and flagellar development in male gametes. Despite being highly expressed in the testis, the exact physiological function of the coiled-coil domain-containing 189 (Ccdc189) gene remain largely unclear. Our research provides a comprehensive and detailed investigation into the localization of CCDC189 protein within the testis seminiferous tubules. CCDC189 specifically expressed in spermatocytes, round spermatids, and elongating spermatids in mouse testis. The deletion of Ccdc189 in mouse leads to male infertility, characterized by significantly reduced sperm counts and motility. Abnormally shaped spermatozoa with irregular tails, exhibiting shortened and twisted morphology, were observed in the seminiferous tubules. Electron microscopy revealed disordered and missing peripheral microtubule doublets (MTD) and outer dense fibers (ODF) in the sperm flagella, accompanied by a consistent absence of central pairs (CP). The knockout of Ccdc189 resulted in oligo-astheno-teratozoospermia, which is characterized by low sperm count and reduced sperm motility and abnormal morphology. Furthermore, we identified poly(A)-binding protein cytoplasmic 1 (PABPC1) and PABPC2 as interacting proteins with CCDC189. These proteins belong to the PABP family and are involved in regulating mRNA translational activity in spermatogenic cells by specifically binding to poly(A) tails at the 3' ends of mRNAs.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"800-814"},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Memorium of Professor Patricia B. Hoyer. 纪念帕特里夏-B-霍耶教授。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-10-10 DOI: 10.1093/biolre/ioae145

Jodi A Flaws, Zelieann Craig, Aileen Keating

引用次数: 0

Loss of CCDC188 causes male infertility with defects in the sperm head–neck connection in mice CCDC188 缺失会导致小鼠精子头颈部连接缺陷，从而导致雄性不育

IF 3.6 2区生物学

Biology of Reproduction Pub Date : 2024-09-18 DOI: 10.1093/biolre/ioae137

Yumiao Qiu, Keisuke Shimada, Kaito Yamamoto, Masahito Ikawa

{"title":"Loss of CCDC188 causes male infertility with defects in the sperm head–neck connection in mice","authors":"Yumiao Qiu, Keisuke Shimada, Kaito Yamamoto, Masahito Ikawa","doi":"10.1093/biolre/ioae137","DOIUrl":"https://doi.org/10.1093/biolre/ioae137","url":null,"abstract":"Acephalic spermatozoa syndrome (ASS) represents a rare genetic and reproductive disease, which is defined as semen composed of mostly headless spermatozoa. The connecting piece in the neck region, also known as the head-to-tail coupling apparatus (HTCA), plays a crucial role in the tight linkage between the sperm head and tail. Dysfunction of this structure can lead to separation of sperm heads and tails, and male infertility. Using the mouse as an experimental model, several proteins have been identified as associated with the HTCA and disruption of these proteins causes acephalic spermatozoa. However, the molecular mechanism underlying this morphologic anomaly and HTCA remains elusive. In this study, we focused on coiled-coil domain containing 188 (Ccdc188), which shows testis-enriched expression. To elucidate the physiological role of CCDC188, we generated a knockout (KO) mouse line using the CRISPR/Cas9 system. Ccdc188 KO male mice were sterile, indicating that CCDC188 is indispensable for male fertility. Most Ccdc188-null spermatozoa were acephalic. Transmission electron microscopy revealed that while the sperm HTCA could assemble properly without CCDC188, the HTCA failed to attach to the nucleus during spermiogenesis, leading to sperm head and neck separation. In addition, we found almost all of the spermatozoa in the cauda epididymis lacked a mitochondrial sheath. Taken together, we demonstrated that CCDC188 plays a crucial role in forming a tight sperm head–neck junction.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":"50 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding recurrent pregnancy loss: insights from comparative proteomics studies 解码复发性妊娠损失：比较蛋白质组学研究的启示

IF 3.6 2区生物学

Biology of Reproduction Pub Date : 2024-09-17 DOI: 10.1093/biolre/ioae134

Katarina Davalieva, Damjan Kocarev, Dijana Plaseska-Karanfilska

{"title":"Decoding recurrent pregnancy loss: insights from comparative proteomics studies","authors":"Katarina Davalieva, Damjan Kocarev, Dijana Plaseska-Karanfilska","doi":"10.1093/biolre/ioae134","DOIUrl":"https://doi.org/10.1093/biolre/ioae134","url":null,"abstract":"Recurrent pregnancy loss (RPL) represents a common disorder that affects up to 2% of the women aiming at childbirth with long-term consequences on family and society. Factors contributing to it in more than half of the cases are still unknown. Comparative proteomic analysis can provide new insights into the biological pathways underlining the pathogenesis of RPL. Until now, chorionic villi, decidua, placenta, endometrium, and maternal blood from women with RPL have been analyzed by comparative proteomics studies. In this review, we aimed to provide a critical evaluation of the published comparative studies of RPL on human samples, gathered by systematic literature search using PubMed and Google Scholar databases. We provide a detailed overview of the analyzed materials, proteomics platforms, proposed candidate biomarkers and altered pathways and processes linked with RPL. The top, most identified and validated biomarker candidates from all studies are discussed, followed by bioinformatics analysis of the available high-throughput data and presentation of common altered processes and pathways in RPL. Finally, future directions aimed at developing new and efficient therapeutic strategies are discussed as well.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":"24 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro reminiscence: uterine programming in vivo affects respective luminal epithelial cells function in vitro†. 体外回忆：子宫体内编程影响各自管腔上皮细胞的体外功能†。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-09-14 DOI: 10.1093/biolre/ioae093

Cecilia Constantino Rocha, Andrey Luiz Lopes Cordeiro, Meghan Campbell, Mariangela Bueno Cordeiro Maldonado, Felipe Alves Correa Carvalho Silva, Alexandra Bennett, Abdul Waheed, Thomas Hansen, Mario Binelli

{"title":"In vitro reminiscence: uterine programming in vivo affects respective luminal epithelial cells function in vitro†.","authors":"Cecilia Constantino Rocha, Andrey Luiz Lopes Cordeiro, Meghan Campbell, Mariangela Bueno Cordeiro Maldonado, Felipe Alves Correa Carvalho Silva, Alexandra Bennett, Abdul Waheed, Thomas Hansen, Mario Binelli","doi":"10.1093/biolre/ioae093","DOIUrl":"10.1093/biolre/ioae093","url":null,"abstract":"In cattle, the endometrium during diestrus and early pregnancy displays cellular responses that are consequences of prior, transient stimuli. Goal was to establish a model to study cellular memory in the endometrium. The hypothesis is that stimuli given to endometrium in vivo are retained as a cellular memory that remains after bovine uterine epithelial cells (BUECs) are isolated, cultured, and further stimulated in vitro. Objectives were to measure BUEC proliferation/migration and responsiveness to recombinant bovine Interferon-tau (rbIFNT) in vitro: among cows that showed estrus (experiment 1 [Exp1]), cows that became or not pregnant to artificial insemination (Exp2), cows that received or not supplemental progesterone (P4; Exp3) and cows that received or not a COX-1/2 inhibitor (Exp4). Only cows that displayed estrus were included in studies. For all experiments endometrial cytology was collected 4 days after estrus, BUECs were cultured, propagated, and submitted to rbIFNT treatment and an in vitro scratch assay. In Exp1, different cows spontaneously grouped according to proliferative/migratory capacity and responsiveness to rbIFNT of their respective BUECs. In Exp2, BUECs from pregnant cows showed greater rbIFNT responsiveness and cellular proliferation. In Exp3, BUECs from cows supplemented with P4 presented inhibited proliferation and increased expression of RSAD2. In Exp4, Flunixin Meglumine modified rbIFNT responsiveness of BUECs in an IFN-signaling pathway-specific manner. In conclusion, physiological and pharmacological stimuli received by the endometrium in vivo were retained as cellular memory in BUECs, persisted in culture, and changed BUEC proliferation/migration and responsiveness to rbIFNT, which are characteristics associated with fertility in cattle.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"600-612"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evidence for metabolism of creatine by the conceptus, placenta, and uterus for production of adenosine triphosphate during conceptus development in pigs†. 在猪的胚胎发育过程中，胚胎、胎盘和子宫代谢肌酸以产生 ATP 的证据。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-09-14 DOI: 10.1093/biolre/ioae088

Carli M Lefevre, Joe W Cain, Avery C Kramer, Heewon Seo, Arianna N Lopez, Nirvay Sah, Guoyao Wu, Fuller W Bazer, Gregory A Johnson

{"title":"Evidence for metabolism of creatine by the conceptus, placenta, and uterus for production of adenosine triphosphate during conceptus development in pigs†.","authors":"Carli M Lefevre, Joe W Cain, Avery C Kramer, Heewon Seo, Arianna N Lopez, Nirvay Sah, Guoyao Wu, Fuller W Bazer, Gregory A Johnson","doi":"10.1093/biolre/ioae088","DOIUrl":"10.1093/biolre/ioae088","url":null,"abstract":"In pigs, the majority of embryonic mortality occurs when free-floating conceptuses (embryos/fetuses and associated placental membranes) elongate, and the uterine-placental interface undergoes folding and develops areolae. Both periods involve proliferation, migration, and changes in morphology of cells that require adenosine triphosphate (ATP). We hypothesize that insufficient ATP in conceptus and uterine tissues contributes to conceptus loss in pigs. Creatine is stored in cells as phosphocreatine for ATP regeneration through the creatine-creatine kinase- phosphocreatine pathway. However, the expression of components of this pathway in pigs has not been examined throughout gestation. Results of qPCR analyses indicated increases in AGAT, GAMT, CKM, CKB, and SLC6A8 mRNAs in elongating porcine conceptuses, and immunofluorescence microscopy localized guanidinoacetate N-methyltransferase, creatine kinase M, and creatine kinase B proteins to the trophectoderm of elongating conceptuses, to the columnar chorionic epithelial cells at the bottom of chorioallantoic troughs, and to endometrial luminal epithelium at the tops of the endometrial ridges of uterine-placental folds on Days 40, 60, and 90 of gestation. Guanidinoacetate N-methyltransferase protein is expressed in endometrial luminal epithelium at the uterine-placental interface, but immunostaining is more intense in luminal epithelium at the bottoms of the endometrial ridges. Results of this study indicate that key elements of the pathway for creatine metabolism are expressed in cells of the conceptus, placenta, and uterus for potential production of ATP during two timepoints in pregnancy with a high demand for energy; elongation of the conceptus for implantation and development of uterine-placental folding during placentation.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"694-707"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Provision of choline chloride to the bovine preimplantation embryo alters postnatal body size and DNA methylation†. 为牛植入前胚胎提供氯化胆碱会改变出生后的体型和 DNA 甲基化。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-09-14 DOI: 10.1093/biolre/ioae092

McKenzie L J Haimon, Eliab Estrada-Cortés, Thiago F Amaral, Hélène Martin, Surawich Jeensuk, Jeremy Block, Daniella Heredia, M Venturini, Camila Santos Rojas, Angela M Gonella-Diaza, Nicolas DiLorenzo, Tracy L Scheffler, Pascal Dufour, Marc-André Sirard, Gabriela Dalmaso de Melo, Ky G Pohler, Peter J Hansen

{"title":"Provision of choline chloride to the bovine preimplantation embryo alters postnatal body size and DNA methylation†.","authors":"McKenzie L J Haimon, Eliab Estrada-Cortés, Thiago F Amaral, Hélène Martin, Surawich Jeensuk, Jeremy Block, Daniella Heredia, M Venturini, Camila Santos Rojas, Angela M Gonella-Diaza, Nicolas DiLorenzo, Tracy L Scheffler, Pascal Dufour, Marc-André Sirard, Gabriela Dalmaso de Melo, Ky G Pohler, Peter J Hansen","doi":"10.1093/biolre/ioae092","DOIUrl":"10.1093/biolre/ioae092","url":null,"abstract":"Choline is a vital micronutrient. In this study, we aimed to confirm, and expand on previous findings, how choline impacts embryos from the first 7 days of development to affect postnatal phenotype. Bos indicus embryos were cultured in a choline-free medium (termed vehicle) or medium supplemented with 1.8 mM choline. Blastocyst-stage embryos were transferred into crossbred recipients. Once born, calves were evaluated at birth, 94 days, 178 days, and at weaning (average age = 239 days). Following weaning, all calves were enrolled into a feed efficiency trial before being separated by sex, with males being slaughtered at ~580 days of age. Results confirm that exposure of 1.8 mM choline chloride during the first 7 days of development alters postnatal characteristics of the resultant calves. Calves of both sexes from choline-treated embryos were consistently heavier through weaning and males had heavier testes at 3 months of age. There were sex-dependent alterations in DNA methylation in whole blood caused by choline treatment. After weaning, feed efficiency was affected by an interaction with sex, with choline calves being more efficient for females and less efficient for males. Calves from choline-treated embryos were heavier, or tended to be heavier, than calves from vehicle embryos at all observations after weaning. Carcass weight was heavier for choline calves and the cross-sectional area of the longissimus thoracis muscle was increased by choline.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"567-579"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PPARG is dispensable for bovine embryo development up to tubular stages†. PPARG 在牛胚胎发育到管状阶段时是不可或缺的。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-09-14 DOI: 10.1093/biolre/ioae083

Alba Pérez-Gómez, Leopoldo González-Brusi, Inés Flores-Borobia, Nuria Martínez De Los Reyes, Adolfo Toledano-Díaz, Antonio López-Sebastián, Julián Santiago Moreno, Priscila Ramos-Ibeas, Pablo Bermejo-Álvarez

{"title":"PPARG is dispensable for bovine embryo development up to tubular stages†.","authors":"Alba Pérez-Gómez, Leopoldo González-Brusi, Inés Flores-Borobia, Nuria Martínez De Los Reyes, Adolfo Toledano-Díaz, Antonio López-Sebastián, Julián Santiago Moreno, Priscila Ramos-Ibeas, Pablo Bermejo-Álvarez","doi":"10.1093/biolre/ioae083","DOIUrl":"10.1093/biolre/ioae083","url":null,"abstract":"Following blastocyst hatching, ungulate embryos undergo a prolonged preimplantation period termed conceptus elongation. Conceptus elongation constitutes a highly susceptible period for embryonic loss, and the embryonic requirements during this process are largely unknown, but multiple lipid compounds have been identified in the fluid nourishing the elongating conceptuses. Peroxisome proliferator-activated receptors mediate the signaling actions of prostaglandins and other lipids, and, between them, PPARG has been pointed out to play a relevant role in conceptus elongation by a functional study that depleted PPARG in both uterus and conceptus. The objective of this study has been to determine if embryonic PPARG is required for bovine embryo development. To that aim, we have generated bovine PPARG knock-out embryos in vitro using two independent gene ablation strategies and assessed their developmental ability. In vitro development to Day 8 blastocyst was unaffected by PPARG ablation, as total, inner cell mass, and trophectoderm cell numbers were similar between wild-type and knock-out D8 embryos. In vitro post-hatching development to D12 was also comparable between different genotypes, as embryo diameter, epiblast cell number, embryonic disk formation, and hypoblast migration rates were unaffected by the ablation. The development of tubular stages equivalent to E14 was assessed in vivo, following a heterologous embryo transfer experiment, observing that the development of extra-embryonic membranes and of the embryonic disk was not altered by PPARG ablation. In conclusion, PPARG ablation did not impaired bovine embryo development up to tubular stages.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"557-566"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 apoptosis increased by hypoxia inducible factor-1 stabilization is counteracted by leptin†. 瘦素可抵消因缺氧诱导因子-1 稳定而增加的胎盘凋亡。

IF 3.1 2区生物学

Biology of Reproduction Pub Date : 2024-09-14 DOI: 10.1093/biolre/ioae095

Nataly de Dios, Rodrigo Riedel, Malena Schanton, Paula Balestrini, Luciano Pérez, Antonio Pérez-Pérez, Tomás Etcheverry, Roberto Casale, Mariana Farina, Víctor Sánchez-Margalet, Julieta Maymó, Cecilia Varone

{"title":"Placental apoptosis increased by hypoxia inducible factor-1 stabilization is counteracted by leptin†.","authors":"Nataly de Dios, Rodrigo Riedel, Malena Schanton, Paula Balestrini, Luciano Pérez, Antonio Pérez-Pérez, Tomás Etcheverry, Roberto Casale, Mariana Farina, Víctor Sánchez-Margalet, Julieta Maymó, Cecilia Varone","doi":"10.1093/biolre/ioae095","DOIUrl":"10.1093/biolre/ioae095","url":null,"abstract":"During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed toward the relevance of hypoxia as modulator of trophoblast cell death. Previous reports have shown that leptin, a placental cytokine, promotes cell survival in both cell culture and placental explant models. The aim of this work is to establish the role of leptin in apoptosis under hypoxic condition in trophoblast cells. In this study, we evaluated the effect of cobalt chloride, a hypoxia mimicking agent that stabilizes the expression of hypoxia-inducible factor-1 alpha, on Swan-71 and human placental explants. Hypoxia chamber was also used to generate 2% oxygen. Apoptosis was determined by the presence of apoptotic nucleus, fragmentation of DNA and Caspase-3 and PARP-1 cleavage. The pro-apoptotic proteins BAX, BID, BAD, and BAK and the anti-apoptotic effectors BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1 were also analyzed. We found that hypoxia-inducible factor-1 alpha stabilization increased the appearance of apoptotic nucleus, fragmentation of DNA, and Caspase-3 and PARP-1 cleavage. Hypoxia mimicking conditions enhanced the expression of pro-apoptotic effectors BAX, BID, BAD, and BAK. Hypoxia-inducible factor-1 alpha stabilization also downregulated the level of BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1. All these apoptotic parameters changes were reversed with leptin treatment. Moreover, we showed that leptin action on apoptosis modulation involves PI3K and MAPK signaling pathways. Obtained data demonstrate that hypoxia-inducible factor-1 alpha stabilization induces apoptosis in human placenta and leptin counteracts this effect, reinforcing its role as a survival cytokine.","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"708-722"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0