Topics and Trends in Most Cited Reproductive Biology and Fertility Papers

Ranked by citations 18 months after publication

Class of 2026 (Papers Published in 2024)

What topics and trends defined most-cited Reproductive Biology and Fertility research in the Class of 2026?

The Class of 2026 highlights a major research shift toward female reproductive aging and polycystic ovary syndrome (PCOS). Studies increasingly focus on oxidative stress and the ovarian microenvironment, leveraging single-cell transcriptomics to map cellular changes. This reflects a concerted effort to understand and therapeutically target the molecular drivers of age-related fertility decline.

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Updated July 17, 2026

At a glance

Field
Reproductive Biology and Fertility
Cohort label
Class of 2026 (2024 publications)
Papers analyzed
7,510
Papers ranked
20
Top topics in ranked papers
Female reproductive aging, Polycystic ovary syndrome, oxidative stress, Granulosa cells
Publication window
Jan 1, 2024 – Dec 31, 2024
Eligibility
Research articles; reviews excluded
Citation window
18 months post-publication
18m citation range
31–89
Data source
OpenAlex · Retrieved July 2026
License
CC BY 4.0

Rankings

20 papers ranked by 18-month citation count

#1 of 7,510
8918m citations

A single-cell atlas of the aging mouse ovary

José V V Isola, Sarah R Ocañas et al.Nature Aging202410.1038/s43587-023-00552-5

Michael B. StoutOklahoma Medical Research Foundation, United States

Female reproductive agingSingle-cell transcriptomicsMouse ovaryoocyte qualityimmune cell infiltrationlymphocyte accumulationflow cytometrystromal fibroblastscollagenase pathway downregulationOvarian fibrosisfollicular cellsCellular stress responsesimmunogenic signalingfibrotic signalingreproductively aged micetranscriptomic changesFollicular depletionShiny-based web application
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#2 of 7,510
6718m citations

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1

Meng Wu, Weicheng Tang et al.Nature Aging202410.1038/s43587-024-00607-1

Jun Dai, Yan Li, Tao Xiang, Shixuan WangHuazhong University of Science and Technology, China

Single-cell transcriptomicsspatial transcriptomicsFemale reproductive agingOocyte agingDNA damage responsegranulosa cells subtypestheca and stromal cells subtypesFOXP1CDKN1A transcriptionPremature ovarian insufficiencySpatiotemporal transcriptomicsage-associated gene expressionOvarian cell atlasFOXP1 silencing
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#3 of 7,510
6718m citations

Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial

Peter J Illingworth et al.Nature Medicine202410.1038/s41591-024-03166-5

Peter IllingworthVirtus Health, Australia

deep learningembryo selectionIn vitro fertilizationiDAScoremorphological assessmentearly-stage blastocystsclinical pregnancy ratenoninferiority trialdouble-blind randomized controlled trialembryo prioritization schememulticenter trial
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#4 of 7,510
6518m citations

Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses

Chen Jin, Xizhe Wang, Jiping Yang et al.Nature Aging202410.1038/s43587-024-00762-5

Chen Jin, Yousin SuhColumbia University Irving Medical Center, United States

single-nuclei multi-omicsFemale reproductive agingsingle-nuclei RNA-seqsingle-nuclei ATAC-seqchromatin accessibilitymTOR signalingCEBPD transcription factorAge at menopausecell-type-specific regulatory networksnon-coding regulatory variantsgene regulatory networksreproductively aged ovariesepigenomic changesfunctional genetic variantsOvarian cell atlastranscriptomic aging signaturesmenopause-associated variantsovary-specific aging pathways
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#5 of 7,510
5518m citations

A conserved fertilization complex bridges sperm and egg in vertebrates

Victoria E Deneke et al.Cell202410.1016/j.cell.2024.09.035

Victoria E. Deneke, Andrea PauliResearch Institute of Molecular Pathology (IMP), Austria

Tmem81Izumo1Spaca6BouncerJUNOAlphaFold-Multimer screentrimeric sperm complexsperm-egg bindingsperm-egg fusionzebrafish fertilizationmouse fertilitymale fertilityconserved fertilization complexvertebrate reproductionegg fertilization factorprotein-protein interactioncross-species conservationspecies-specific egg proteins
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#7 of 7,510
5118m citations

The cycling and aging mouse female reproductive tract at single-cell resolution

Ivana Winkler et al.Cell202410.1016/j.cell.2024.01.021

Duncan T. Odom, Ângela GonçalvesGerman Cancer Research Center (DKFZ), Germany

mouse female reproductive tractsingle-cell resolutionEstrous cycleFemale reproductive agingovaryoviductuterusvaginaSingle-cell transcriptomicsepithelial cellsstromal cellsimmune cellshormonal regulationCell atlasage-related changescycling dynamicsreproductive tissues
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#9 of 7,510
4518m citations

The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice

Chuyu Yun, Sen Yan et al.Nature Metabolism202410.1038/s42255-024-01041-8

Rong Li, Changtao Jiang, Jie Qiao, Yanli PangPeking University Third Hospital, China

agmatineFXR agonistPolycystic ovary syndromemicrobial metabolitegut microbiotafarnesoid X receptorPCOS mouse modelmicrobiome-host interactionmetabolite signalingnuclear receptor activationovarian dysfunctiongut-ovary axisbacterial metabolismEndocrine disruption
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#10 of 7,510
4318m citations

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients

Pavan Gill et al.Human Reproduction202410.1093/humrep/deae040

Emre SeliIVIRMA Global Research Alliance, United States

Implantation failureeuploid blastocyst transferpreimplantation genetic testing for aneuploidyLive birth rateclinical pregnancy ratecumulative live birth rateImplantation ratesingle embryo transferendometrial receptivity assayintracavitary uterine pathologycongenital uterine anomaliesadenomyosiscommunicating hydrosalpinxendometrial thicknesstrophectoderm biopsyblastocyst quality gradingembryonic aneuploidy
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#11 of 7,510
4018m citations

3D reconstruction of a gastrulating human embryo

Zhenyu Xiao et al.Cell202410.1016/j.cell.2024.03.041

Xiaoyan Wang, Yulei Wei, Jingtao Guo, Leqian YuState Key Laboratory of Stem Cell and Reproductive Biology, China

3D reconstructiongastrulating human embryogastrulationEmbryonic developmentCarnegie stageprimitive streakEpiblastHypoblastimaging techniquesdevelopmental biologyembryonic morphologyspatial reconstruction
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#12 of 7,510
4018m citations

Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing

Andrea S K Jones et al.Science Advances202410.1126/sciadv.adm7506

Andrea Jones, D. Ford Hannum, Jun Z. Li, Ariella ShikanovUniversity of Michigan, United States

spatial transcriptomicsSingle-cell transcriptomicshuman ovaryoocytestheca cellsGranulosa cellsFollicle developmentOvarian cortexovarian medullahormone remodelingextracellular matrix remodelingimmune cell subtypesmorphologically guided samplingpremenopausal donorsoocyte-specific genestheca-specific genesgranulosa-specific genesOvarian cell atlas
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#13 of 7,510
4018m citations

The first two blastomeres contribute unequally to the human embryo

Sergi Junyent et al.Cell202410.1016/j.cell.2024.04.029

Magdalena Zernicka‐GoetzCalifornia Institute of Technology, United States

2-cell stage blastomeresclonal imbalanceprospective lineage tracinglive imagingnon-invasive cell labelingEpiblastHypoblasttrophectodermcell internalization8-to-16-cell stage transitionfirst cell to dividecell division dynamicscell internalization bottleneckclonal asymmetryEmbryonic development
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#14 of 7,510
3418m citations

Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice

Ye Chen et al.Redox Biology202410.1016/j.redox.2024.103195

Wei MaCapital Medical University, China

iron accumulationOvarian microenvironmentoocyte qualityovarian reserve declineheme oxygenase 1 (HO-1)ferritin heavy chain (FTH)ferritin light chain (FTL)mitochondrial ferritin (FTMT)divalent metal transporter 1 (DMT1)ferroportin1 (FPN1)iron regulatory proteins (IRP1 and IRP2)transferrin receptor 1 (TFR1)ferritinophagymitophagylipid peroxidationmitochondrial dysfunctiondeferoxamine (DFO)iron chelationoocyte aneuploidyFemale reproductive aging
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#15 of 7,510
3318m citations

Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators

Bofeng Liu, Yuanlin He, Xiaotong Wu, Zili Lin, Jing Ma et al.Nature Cell Biology202410.1038/s41556-024-01422-x

Jing Li, Wei XieTsinghua University, China

putative enhancersmouse oocytesearly embryosTCF3TCF12Follicle developmentenhancer mappingoocyte developmentEmbryonic developmenttranscription factor regulationchromatin accessibilitydevelopmental gene regulation
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#16 of 7,510
3318m citations

Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging

Shiyun Long, Yunchao Zheng et al.Communications Biology202410.1038/s42003-024-06888-x

Yanmei Dou, Min JiangZhejiang University, China

mitochondrial DNA copy numberReactive oxygen speciesoocyte maturationFemale reproductive agingSod2 conditional knockoutprimordial folliclesmitochondrial matrix ROSOXPHOS complex IImtDNA-encoded mRNAmtDNA mutation loadmtSSB proteinmtDNA replicationoxidative stressoocyte qualitymaternal mtDNA transmission
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#17 of 7,510
3318m citations

M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis

Xiaolan Zhu, Wenxin Li, Minjun Lu et al.Journal of Nanobiotechnology202410.1186/s12951-024-02583-5

Xiaolan ZhuThe Fourth Affiliated Hospital of Jiangsu University, China

Premature ovarian insufficiencyhuman umbilical cord mesenchymal stem cell-derived exosomescircBRCA1FTOm6A demethylationmiR-642a-5pFOXO1Granulosa cellsoxidative stressmitochondrial dysfunctionovarian reserve functionFollicular depletionReactive oxygen speciessenescence-associated β-galactosidase stainingcompeting endogenous RNAEstrous cyclereproductive hormonesoxygen consumption rateGene Expression Omnibus database
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#18 of 7,510
3218m citations

Semaglutide Alleviates Ovary Inflammation via the AMPK/SIRT1/NF‑κB Signaling Pathway in Polycystic Ovary Syndrome Mice

Mei Liu, Sili Guo, Xiaohan Li et al.Drug Design Development and Therapy202410.2147/dddt.s484531

Mei Liu, Sili Guo, Xiaohan LiBinzhou Medical University Hospital, China

semaglutideGLP-1 receptor agonistsPolycystic ovary syndromeovarian inflammationAMPK/SIRT1/NF-κB signaling pathwaydehydroepiandrosteroneC57BL/6 miceCYP19A1CYP17A1StARTNF-αIL-6IL-1βNF-κBAMPK phosphorylationSIRT1IκBα phosphorylationinsulin resistancefollicular cystic dilationEstrous cycle
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#19 of 7,510
3218m citations

Mechanisms of minor pole–mediated spindle bipolarization in human oocytes

Tianyu Wu, Yuxi Luo, Meiling Zhang, Biaobang Chen et al.Science202410.1126/science.ado1022

Tianyu Wu, Yuxi Luo, Meiling Zhang, Biaobang Chen, Wen Li, Qing Sang, Lei WangFudan University, China

spindle bipolarizationhuman oocytesmultipolar intermediatesminor poleskinetochore clustersmicrotubule masschromosome segregationHAUS6KIF11KIF18Ahigh-resolution imaginginfertile patientsoocyte defectsembryo defectsgene mutations
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#20 of 7,510
3118m citations

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey

Kathleen Duffin et al.Human Reproduction Open202410.1093/hropen/hoae010

Rod T. MitchellUniversity of Edinburgh, United Kingdom

Fertility preservationtesticular tissue cryopreservationpre-pubertal boysimmature testicular tissuegonadotoxic treatmentORCHID-NET consortiumdimethylsulphoxide cryoprotectantmalignant and non-malignant indicationsFertility restorationquality assurance standardstissue storage protocolsfollow-up practice variabilityconsent for research on stored tissueclinical application of stored tissueinternational survey studyharmonization of clinical protocolschildhood cancer survivorsfunding source variationtissue function evaluation
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Dominant research themes and year-over-year shifts in Reproductive Biology and Fertility

What Topics Define the Class of 2026?

The Class of 2026 in Reproductive Biology and Fertility is heavily focused on addressing reproductive aging and prevalent endocrine disorders. "Female reproductive aging" and "Polycystic ovary syndrome" (PCOS) are the most dominant themes, indicating a major research emphasis on understanding age-related fertility decline and complex metabolic-reproductive conditions. A significant cluster of research investigates the cellular and molecular mechanisms underlying these issues, highlighted by prominent concepts like "oxidative stress", "Reactive oxygen species", and the "Ovarian microenvironment". Studies frequently center on "Granulosa cells", which play a critical role in follicle development and are highly susceptible to stress and aging. Clinical interventions remain central to the field, with extensive focus on "In vitro fertilization", "Intracytoplasmic sperm injection", and "Ovarian stimulation" aimed at overcoming these biological hurdles. The widespread use of "Single-cell transcriptomics" underscores a methodological shift toward high-resolution profiling of reproductive tissues, enabling researchers to map the ovarian microenvironment and cellular states with unprecedented detail. Overall, the current landscape reflects a concerted effort to connect molecular dysfunction—such as oxidative damage and endocrine disruption—with practical strategies to improve fertility outcomes in the face of aging and conditions like PCOS.

Leading research themes
Leading research themes

How Did Topics Shift from the Class of 2025 to the Class of 2026?

The transition from the Class of 2025 to the Class of 2026 reveals a pronounced shift toward studying the molecular drivers of reproductive decline, with "Female reproductive aging" experiencing a striking threefold increase in prominence. This surge is accompanied by a heightened focus on the cellular mechanisms of aging and damage, evidenced by significant rises in "oxidative stress" (twofold increase) and "Reactive oxygen species". Polycystic ovary syndrome (PCOS) also saw continued growth, solidifying its position as a central challenge in the field. Notably, advanced molecular mapping has rapidly gained traction, with the concept of the "Ovarian cell atlas" emerging prominently, alongside increased applications of single-cell transcriptomics to dissect the ovarian microenvironment. Conversely, some previously dominant topics have seen a relative decline; attention to "Premature ovarian insufficiency" and "Male infertility" decreased, suggesting a reallocation of research focus toward the ubiquitous challenge of age-related female fertility decline. Overall, these shifts highlight a field increasingly leveraging high-resolution molecular techniques and focusing on oxidative damage to understand and mitigate the effects of reproductive aging and endocrine disorders.

How topics shifted year over year
How topics shifted year over year
Methodology

PRI identifies high-impact research using a transparent, topic-agnostic framework applied consistently across scientific domains. Bibliographic records are drawn from OpenAlex, including publication dates, citation relationships, and document types.

This ranking covers the Class of 2026 cohort: journal articles published in 2024. Reviews and other non-article document types are excluded to ensure comparability.

Research impact is quantified with an 18-month post-publication citation window—the number of citing works published within 18 months of each paper's publication date. This metric captures early impact while controlling for publication age.

An LLM-based relevance classifier then reviews each candidate's title and abstract to confirm substantive alignment with the target domain. Only papers classified as relevant appear in the final ranking.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459

Full methodologyGitHubbioRxiv preprint

Cite this ranking

Pepkio Research Index (PRI). Topics and Trends in Most Cited Reproductive Biology and Fertility Papers, Class of 2026. https://pri.pepkio.com/top-papers/reproductive-biology-and-fertility/2026. Accessed 2026-07-17.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459