Molecular Reproduction and Development最新文献

{"title":"A tribute: David Lorn Garbers, PhD (1944–2006)","authors":"Harvey Florman,&nbsp;Gregory S. Kopf","doi":"10.1002/mrd.23769","DOIUrl":"10.1002/mrd.23769","url":null,"abstract":"<p>We are honored to present this special issue of <i>Molecular Reproduction and Development</i> in tribute to David Garbers on occasion of the year of what would have been his 80th birthday, a biochemist whose scientific contributions have significantly advanced the field of reproductive biology and have also led to foundational work in several other areas of medicine. Dave left us too soon and the biomedical research community lost a great scientist, mentor, friend, and family man. As scientific colleagues (HMF; GSK) and a mentee (GSK) of David, we believe that the reviews published in this special issue by our scientific colleagues reflect Dave's foundational work in the field of sperm signal transduction, metabolism, acrosomal exocytosis, chemotaxis, as well as his influence in areas of testicular function and contraception (Garbers, <span>1989</span>). This breadth of contributions by Dave and his lab to the field of reproductive biology/medicine provides a suitable historical background for all young investigators in this field who had never met Dave nor were familiar with his impact on this and other scientific fields.</p><p>One anecdote encapsulates Dave's approach to science. He once spoke of the auriferous gravels of the Sierra Nevada range. There were reports that during the early days of the California gold rush one simply had to wade through streambeds in the mountains and pick up nuggets lying in plain view. The trick was that it was difficult to reach those rivers. The auriferous stream of science, he went on, was the research literature of the early years of the 20th century, replete with value but limited by the methods available at the time. Of course, the key to finding those nuggets was curiosity and scholarship. A case in point was Dave's work on sea urchin egg activation of sperm. In 1928, James Gray (1891–1975) found that eggs of the common sea urchin, <i>Echinus esculentus</i>, released factors into sea water that activated oxygen consumption by conspecific sperm, but the biochemical techniques of the time were not up to the task of identifying the active agents (Gray, <span>1928</span>). Dave revisited this with the tools of 1960s biochemistry and the result was the characterization of the sperm-activating peptides, resact and speract. That was Dave-curious about the history of his field and adventurous enough to see the possibilities hidden therein. That approach served him well.</p><p>David grew up on the family farm in LaCrosse, Wisconsin and one cannot help to think that his love for the field of reproductive biology was influenced during his childhood while helping the family manage their farm. After receiving his bachelor's degree in animal science at the University of Wisconsin, Madison, he remained at Wisconsin and went on to obtain a masters in reproductive biology and a PhD in biochemistry under the tutelage of National Academy of Sciences members Drs. Neal First and Henry Lardy, respectively. During his postgra","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.23769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of berberine combined with metformin on autophagy in polycystic ovary syndrome by regulating AMPK/AKT/mTOR pathway","authors":"Ruiying Jin,&nbsp;Aixue Chen,&nbsp;Yongju Ye,&nbsp;Yuefang Ren,&nbsp;Jiali Lu,&nbsp;Feilan Xuan,&nbsp;Weimei Zhou","doi":"10.1002/mrd.23768","DOIUrl":"10.1002/mrd.23768","url":null,"abstract":"<p>The pathologic mechanism of polycystic ovary syndrome (PCOS) is related to increased autophagy of granulosa cells. Both berberine and metformin have been shown to improve PCOS, but whether the combination of berberine and metformin can better improve PCOS by inhibiting autophagy remains unclear. PCOS models were constructed by injecting dehydroepiandrosterone into rats, and berberine, metformin or berberine combined with metformin was administered to rats after modeling. Rats' body weight and ovarian weight were measured before and after modeling. Histopathological examination of ovarian tissue and estrous cycle analysis of rats were performed. Insulin resistance, hormone levels, oxidative stress, and lipid metabolism in PCOS rats were assessed. Expression of the AMPK/AKT/mTOR pathway and autophagy-related proteins was analyzed by Western blot assays. Granulosa cells were isolated from rat ovarian tissue and identified by immunofluorescence staining followed by transmission electron microscopy analysis. Berberine combined with metformin reduced the body weight and ovarian weight of PCOS rats, increased the number of primordial and primary follicles, decreased the number of secondary and atretic follicles, normalized the estrous cycle, and improved insulin resistance, androgen biosynthesis, oxidative stress and lipid metabolism disorders, and increased estrogen production. In addition, berberine combined with metformin reduced the number of autophagosomes in granulosa cells, which may be related to AMPK/AKT/mTOR pathway activation, decreased Beclin1 and LC3II/LC3I levels, and increased p62 expression. Berberine combined with metformin could inhibit autophagy by activating the AMPK/AKT/mTOR pathway in PCOS, indicating that berberine combined with metformin is a potential treatment strategy for PCOS.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clusterin expression and distribution in spermatozoa as predictor of male fertility","authors":"María Hernández-Herrador,&nbsp;García-Aranda Marilina,&nbsp;María Luisa Hortas,&nbsp;Silvia Carrillo-Lucena,&nbsp;Zaira Caracuel,&nbsp;José Antonio Castilla-Alcalá,&nbsp;Desirée Martín-García,&nbsp;Maximino Redondo","doi":"10.1002/mrd.23764","DOIUrl":"10.1002/mrd.23764","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Clusterin (CLU), one of the main glycoproteins in mammalian semen and the male reproductive tract, plays a role in spermatogenesis and sperm maturation. Given the poor reliability of classic seminal studies in determining male-fertilizing capacity and the differences in CLU abundance between normal and abnormal spermatozoa, we investigated the potential value of <i>mRNA-CLU</i> levels and protein distribution in spermatozoa as markers of sperm quality and predictors of male fertility. This multicenter study included 90 patients undergoing in vitro fertilization (IVF) treatment with their partners, and a control group of 36 fertile males with normal seminograms. We assessed the relationship between IVF treatment outcomes, seminogram variables, <i>mRNA-CLU</i> levels by quantitative real-time-PCR and CLU distribution by immunostaining in spermatozoa. Our study reveals CLU staining in the acrosome (<i>p</i> = 0.002, OR 14.8, 95% CI: 2.7–79.3) and <i>mRNA-CLU</i> levels (<i>p</i> = 0.005, OR 10.85, 95% CI: 2.0–57.4) as independent risk factors for pregnancy failure, irrespective of traditional seminogram variables. Additionally, our results suggest that CLU, and specially its secreted isoform, constitutes a component of the protein pool that human spermatozoa can produce during its maturation process, exhibiting a variable abundance and distribution in spermatozoa from fertile men compared to those in patients with altered seminograms and infertile patients with normal seminograms. Our study is the first to identify <i>mRNA-CLU</i> levels and CLU immunostaining in the spermatozoa acrosome as independent risk factors for pregnancy failure, with distribution patterns correlating with sperm maturity and seminogram alterations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen influences the transzonal projection assembly of cumulus-oocyte complexes through G protein-coupled estrogen receptor during goat follicle development","authors":"Rui Xu,&nbsp;Dongxu Wen,&nbsp;Lu Yin,&nbsp;Yaju Tang,&nbsp;Sihai Lu,&nbsp;Yan Gao,&nbsp;Meng-Hao Pan,&nbsp;Bin Han,&nbsp;Baohua Ma","doi":"10.1002/mrd.23763","DOIUrl":"10.1002/mrd.23763","url":null,"abstract":"<p>Estrogen is an important hormone that plays a role in regulating follicle development and oocyte maturation. Transzonal projections (TZPs) act as communication bridges between follicle somatic cells and oocytes, and their dynamic changes are critical for oocyte development and maturation. However, the roles and mechanisms of estrogen in regulating TZPs during follicular development are not yet understood. We found that the proportion of oocytes spontaneously resuming meiosis increases as the follicle grows, which is accompanied by rising estrogen levels in follicles and decreasing TZPs in cumulus-oocyte complex. To further explore the effect of elevated estrogen levels on TZP assembly, additional estrogen was added to the culture system. The increased estrogen level significantly decreased the mRNA and protein expression levels of TZP assembly-related genes. Subsequent research revealed that TZP regulation by estrogen was mediated by the membrane receptor GPER and downstream ERK1/2 signaling pathway. In summary, our study suggests that estrogen may regulate goat oocyte meiosis arrest by decreasing TZP numbers via estrogen-mediated GPER activation during follicle development.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the effect of photoperiodic cues in transducing kisspeptin-melatonin circuit during the pubertal onset in common carp","authors":"Nehareeka Dan,&nbsp;Harsh Shah,&nbsp;Himadri Bhatt,&nbsp;Rahul Ladumor,&nbsp;Ankita Salunke,&nbsp;A. V. Ramachandran,&nbsp;Parth Pandya","doi":"10.1002/mrd.23744","DOIUrl":"10.1002/mrd.23744","url":null,"abstract":"<p>This study unravels the intricate interplay between photoperiod, melatonin, and kisspeptin to orchestrate the pubertal onset of Common carp. Female fingerlings exposed to long days (LD) exhibited a hormonal crescendo, with upregulated hypothalamic-pituitary-ovarian (HPO) axis genes (<i>kiss1</i>, <i>kiss1r</i>, <i>kiss2</i>, <i>gnrh2</i>, <i>gnrh3</i>) and their downstream targets (<i>lhr</i>, <i>fshr</i>, <i>ar1</i>, <i>esr1</i>). However, the expression of the melatonin receptor (<i>mtnr1a</i>) diminished in LD, suggesting a potential inhibitory role. This hormonal symphony was further amplified by increased activity of key transcriptional regulators (<i>gata1</i>, <i>gata2</i>, <i>cdx1</i>, <i>sp1</i>, <i>n-myc</i>, <i>hoxc8</i>, <i>plc</i>, <i>tac3</i>, <i>tacr3</i>) and decreased expression of delayed puberty genes (<i>mkrn1</i>, <i>dlk1</i>). In contrast, short days (SD) muted this hormonal chorus, with decreased <i>gnrh</i> gene and regulator expression, elevated <i>mtnr1a</i>, and suppressed gonadal development. In in-vitro, estradiol mimicked the LD effect, boosting <i>gnrh</i> and regulator genes while dampening <i>mtnr1a</i> and melatonin-responsive genes. Conversely, melatonin acted as a conductor, downregulating <i>gnrh</i> and regulator genes and amplifying <i>mtnr1a</i>. Our findings illuminate the crucial roles of melatonin and kisspeptin as opposing forces in regulating pubertal timing. LD-induced melatonin suppression allows the kisspeptin symphony to flourish, triggering GnRH release and, ultimately, gonadal maturation. This delicate dance between photoperiod, melatonin, and kisspeptin orchestrates common carp's transition from juvenile to reproductive life.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front Cover Image, Volume 91, Issue 5, May 2024","authors":"R. Antonio Gomez,&nbsp;Romano Dallai,&nbsp;Dylan J. Sims-West,&nbsp;David Mercati,&nbsp;Rita Sinka,&nbsp;Yasir Ahmed-Braimah,&nbsp;Scott Pitnick,&nbsp;Steve Dorus","doi":"10.1002/mrd.23761","DOIUrl":"https://doi.org/10.1002/mrd.23761","url":null,"abstract":"<p>Cover Caption: The cover image is based on the Research Article <i>Proteomic diversification of spermatostyles among six species of whirligig beetles</i> by Roberto Gomez et al., https://doi.org/10.1002/mrd.23745.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.23761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141091366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic diversification of spermatostyles among six species of whirligig beetles","authors":"R. Antonio Gomez,&nbsp;Romano Dallai,&nbsp;Dylan J. Sims-West,&nbsp;David Mercati,&nbsp;Rita Sinka,&nbsp;Yasir Ahmed-Braimah,&nbsp;Scott Pitnick,&nbsp;Steve Dorus","doi":"10.1002/mrd.23745","DOIUrl":"10.1002/mrd.23745","url":null,"abstract":"<p>Seminal fluid protein composition is complex and commonly assumed to be rapidly divergent due to functional interactions with both sperm and the female reproductive tract (FRT), both of which evolve rapidly. In addition to sperm, seminal fluid may contain structures, such as mating plugs and spermatophores. Here, we investigate the evolutionary diversification of a lesser-known ejaculate structure: the spermatostyle, which has independently arisen in several families of beetles and true bugs. We characterized the spermatostyle proteome, in addition to spermatostyle and FRT morphology, in six species of whirligig beetles (family Gyrinidae). Spermatostyles were enriched for proteolytic enzymes, and assays confirmed they possess proteolytic activity. Sperm-leucylaminopeptidases (S-LAPs) were particularly abundant, and their localization to spermatostyles was confirmed by immunohistochemistry. Although there was evidence for functional conservation of spermatostyle proteomes across species, phylogenetic regressions suggest evolutionary covariation between protein composition and the morphology of both spermatostyles and FRTs. We postulate that S-LAPs (and other proteases) have evolved a novel structural role in spermatostyles and discuss spermatostyles as adaptations for delivering male-derived materials to females.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.23745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between embryo morphokinetic development and intracytoplasmic sperm injection with epididymal sperm via time-lapse imaging","authors":"Edson Borges Jr.,&nbsp;Daniela Braga,&nbsp;Rodrigo Provenza,&nbsp;Assumpto Iaconelli Jr.,&nbsp;Amanda Setti","doi":"10.1002/mrd.23747","DOIUrl":"10.1002/mrd.23747","url":null,"abstract":"<p>The objective of this study was to investigate the impact of sperm source on embryo morphokinetics and the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles by considering the clustering of data (multiple embryos per patient that share a comparable developmental timing). This matched cohort study was performed at a private university–affiliated in vitro fertilization center. Women who underwent ICSI with epididymal sperm between January 2019 and December 2020 (the percutaneous epididymal sperm aspiration group, <i>n</i> = 32 cycles) were matched with women who underwent ICSI with ejaculated sperm because of idiopathic male factor infertility (the male factor infertility [MFI] group, <i>n</i> = 32 cycles) or female infertility (the control group, <i>n</i> = 32 cycles). Embryos were cultured in a time-lapse imaging incubator, and morphokinetic development was recorded and compared among the groups. Significantly slower divisions were observed in embryos derived from epididymal sperm than in those derived from the MFI and control groups. Embryos derived from epididymal sperm had a significantly lower KIDScore (3.1 ± 0.2) than did those derived from ejaculated spermatozoa from the MFI (5.4 ± 0.1) and control (5.6 ± 0.2, <i>p</i> &lt; 0.001) groups. Epididymal sperm-derived embryos showed a significantly greater occurrence of multinucleation (23.2%) than did those derived from ejaculated sperm from the MFI and control groups (2.8% and 3.7%, <i>p</i> &lt; 0.001, respectively). Epididymal sperm-derived embryos were significantly more likely to undergo direct or reverse cleavage (11.1%) than ejaculated sperm-derived embryos in the control group (4.3%, <i>p</i> = 0.001). In conclusion, delayed cell cleavage and increased incidences of blastomere multinucleation and abnormal cleavage patterns are observed when epididymal-derived sperm are used for ICSI.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of KANSL3 leads to defective inner cell mass and early embryonic lethality","authors":"Ashmita Chander,&nbsp;Jesse Mager","doi":"10.1002/mrd.23760","DOIUrl":"10.1002/mrd.23760","url":null,"abstract":"<p>e–Lysine acetylation is a prominent histone mark found at transcriptionally active loci. Among many lysine acetyl transferases, nonspecific lethal complex (NSL) members are known to mediate the modification of histone H4. In addition to histone modifications, the KAT8 regulatory complex subunit 3 gene (<i>Kansl3</i>), a core member of NSL complex, has been shown to be involved in several other cellular processes such as mitosis and mitochondrial activity. Although functional studies have been performed on NSL complex members, none of the four core proteins, including <i>Kansl3</i>, have been studied during early mouse development. Here we show that homozygous knockout <i>Kansl3</i> embryos are lethal at peri-implantation stages, failing to hatch out of the zona pellucida. When the zona pellucida is removed in vitro, <i>Kansl3</i> null embryos form an abnormal outgrowth with significantly disrupted inner cell mass (ICM) morphology. We document lineage-specific defects at the blastocyst stage with significantly reduced ICM cell number but no difference in trophectoderm cell numbers. Both epiblast and primitive endoderm lineages are altered with reduced cell numbers in null mutants. These results show that <i>Kansl3</i> is indispensable during early mouse embryonic development and with defects in both ICM and trophectoderm lineages.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylbutyric acid inhibits hypoxia-induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF-4/CHOP pathway","authors":"Yinfeng Li,&nbsp;Yongjie Guo,&nbsp;Dan Wu,&nbsp;Ling Ai,&nbsp;Rongrong Wu,&nbsp;Zepeng Ping,&nbsp;Kangyuan Zhu","doi":"10.1002/mrd.23742","DOIUrl":"https://doi.org/10.1002/mrd.23742","url":null,"abstract":"<p>Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4-PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4-PBA restored hypoxia-induced trophoblast viability, inhibited HIF-1α protein expression, inflammation, and PERK/ATF-4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4-PBA decreased hypoxia-induced apoptosis in trophoblasts. The results of the JC-1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4-PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin-1, LC3II, and decreased p62 were seen in hypoxia-stimulated cells. These changes were reversed by 4-PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4-PBA on the viability, apoptosis, and autophagosome number of hypoxia-induced trophoblasts. In summary, 4-PBA reduces autophagy and apoptosis via the PERK/ATF-4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4-PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}