Advances in Reproductive Biology: Cellular and Molecular Mechanisms

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 30 October 2026 | Viewed by 8727

Special Issue Editors

Biology Department, Universidad Autonoma of Madrid, C/Darwin nº 2, 28049 Madrid, Spain
Interests: NHEJ; DBS; sperm; fertility; polymorphism; SNP; oxidative stress

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Guest Editor
Research and Development, STGenetics, Navasota, TX, USA
Interests: sperm; fertility; sex-sorting; flow cytometry

Special Issue Information

Dear Colleagues,

Reproductive biology is undergoing a rapid transformation, with major advancements being made in the cellular and molecular mechanisms that govern fertility, development, and reproductive health. Recent research has unveiled critical insights into gametogenesis, fertilization, embryo implantation, and early embryonic development. Cutting-edge technologies, including single-cell sequencing, CRISPR-based genome editing, and organoid models, are reshaping our understanding of reproductive processes at an unprecedented level. Additionally, the molecular pathways regulating hormonal signaling, epigenetic modifications, and cellular interactions are revealing novel therapeutic targets for infertility and reproductive disorders. This Special Issue will bring together innovative research that explores these fundamental biological processes, bridging basic science and clinical applications in reproductive medicine.

Dr. Rosa Roy
Dr. Clara González-Marín
Guest Editors

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Keywords

  • gametogenesis
  • fertilization
  • embryo implantation
  • reproductive genetics
  • epigenetics in reproduction
  • hormonal signaling
  • stem cells and reproduction
  • assisted reproductive technologies (ARTs)
  • molecular fertility regulation
  • reproductive health innovations

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Published Papers (6 papers)

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Research

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21 pages, 2684 KB  
Article
RNA-Seq Analysis of Human Cumulus Cells Identifies Angiogenic Pathways Associated with Infertility
by Alejandro Baratas, Victoria Pérez-Quiroga, Rosario Planello, Mónica Aquilino, Magdalena Serrano, Moisés de la Casa, Yosu Franco-Iriarte and Rosa Roy
Cells 2026, 15(8), 677; https://doi.org/10.3390/cells15080677 - 11 Apr 2026
Viewed by 417
Abstract
Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. [...] Read more.
Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. In the present study, we performed RNA-seq on CCs from healthy oocyte donors and infertile patients, utilizing a multi-pipeline bioinformatic approach (STAR-Cufflinks, TopHat-HTSeq, and HISAT2-StringTie) to establish a high-confidence, exploratory transcriptomic profile. A set of 234 differentially expressed genes (DEGs) consistently identified across pipelines was obtained, with functional enrichment highlighting blood vessel morphogenesis and angiogenesis as primary drivers of transcriptomic divergence between groups. RT-qPCR validation in individual samples confirmed statistically significant differences for ANKRD22 (upregulated) and E2F7 (downregulated) in infertile patients, while other angiogenesis-related genes, including ANGPT1, ANGPT2 and THBS1, showed consistent but non-significant expression trends, suggesting alterations in angiogenesis-related processes within the follicular microenvironment. These findings support the presence of coordinated angiogenesis-related alterations in cumulus cells and provide a basis for future studies exploring their potential relevance in oocyte competence and ART outcomes. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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20 pages, 8911 KB  
Article
SGK1 Is Upregulated in Retained Placenta and Mediates Estradiol Effects in Bovine Endometrial Cells
by Ruiqing Wang, Meng Wei, Wei Niu, Jingxiao Chen, Jinghong Nan, Yong Zhang, Xingxu Zhao and Qi Wang
Cells 2026, 15(6), 558; https://doi.org/10.3390/cells15060558 - 20 Mar 2026
Viewed by 450
Abstract
Retained placenta (RP) is a significant postpartum complication in dairy cows. Although abnormal estradiol (E2) levels are implicated, the underlying cellular mechanisms remain poorly defined. Through RNA-seq analysis of postpartum blood from cows with or without RP, we identified Serum and [...] Read more.
Retained placenta (RP) is a significant postpartum complication in dairy cows. Although abnormal estradiol (E2) levels are implicated, the underlying cellular mechanisms remain poorly defined. Through RNA-seq analysis of postpartum blood from cows with or without RP, we identified Serum and Glucocorticoid-regulated Kinase 1 (SGK1) as a differentially expressed gene candidate. Analysis of fetal cotyledonary tissues revealed that SGK1 expression was significantly elevated in these tissues, concomitant with markers of suppressed apoptosis, increased levels of tight junction proteins, and an inhibited epithelial–mesenchymal transition (EMT) phenotype. To explore a potential mechanistic link between E2 and these cellular alterations, we investigated the E2-SGK1 axis in bovine endometrial epithelial cells in vitro. E2 treatment upregulated SGK1 expression, reduced apoptosis, increased tight junction protein levels, and suppressed EMT. Conversely, SGK1 knockdown induced apoptosis, disrupted tight junctions, and impaired EMT. Notably, E2 could not rescue the apoptosis and EMT alterations in SGK1-knockdown cells, indicating that SGK1 is a critical mediator of these E2 effects in this cellular model. Based on these initial correlative findings in tissues, combined with the subsequent mechanistic experiments in cells, we propose a novel model whereby dysregulation of the E2- SGK1 axis could contribute to RP pathogenesis by stabilizing the placental interface. Our findings provide the first experimental evidence linking SGK1 to RP and establish a foundation for future in vivo validation. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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23 pages, 2292 KB  
Article
Potential Proteins Associated with Canine Epididymal Sperm Motility
by Marzena Mogielnicka-Brzozowska, Aleksandra Wiktoria Cichowska-Likszo, Pawel Likszo, Leyland Fraser, Weronika Popielarczyk, Julia Pieklik, Maja Kamińska and Gaia Cecilia Luvoni
Cells 2026, 15(1), 85; https://doi.org/10.3390/cells15010085 - 4 Jan 2026
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Abstract
The maturation and motility of epididymal sperm (ES) cells are largely driven by changes in protein expression. This study aimed to analyze the proteomic profile of canine (Canis lupus familiaris) ES across groups characterized by different progressive motility (PMOT) values to [...] Read more.
The maturation and motility of epididymal sperm (ES) cells are largely driven by changes in protein expression. This study aimed to analyze the proteomic profile of canine (Canis lupus familiaris) ES across groups characterized by different progressive motility (PMOT) values to identify motility-related sperm proteins (MRSPs). ES were obtained from the epididymal semen of 19 dogs. The motility and movement parameters of ejaculated sperm (ES) were evaluated using computer-assisted semen analysis (CASA). Samples were classified into two groups: good sperm motility (GSM), defined as PMOT% ≥ 55%, and poor sperm motility (PSM), defined as PMOT < 55%. Principal component analysis (PCA) of the first two components could explain 88.1% of the total variance between the GSM and PSM groups. Protein profiling of ES was performed using NanoUPLC-Q-TOF/MS. Significant statistical differences were demonstrated between the GSM and PSM groups for the TMOT (p = 0.039) and PMOT (p < 0.001). For five common proteins, their abundance was estimated to be higher in the GSM group than in the PSM group: ACTB (p = 0.2732), CRISP2 (p = 0.1558), LTF (p = 0.2661) and significantly higher: ce10 (p = 0.009) and NPC2 (p < 0.0044). These findings may be used to develop diagnostic MRSP-based tests related to ES quality in assisted reproduction techniques in dogs. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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17 pages, 4780 KB  
Article
The Generation of a Testicular Peritubular Cell Line from Giant Pandas (Ailuropoda melanoleuca)
by Xueni You, Yuren Wang, Yuliang Liu, Rong Hou, Yi Zheng and Junhui An
Cells 2025, 14(18), 1426; https://doi.org/10.3390/cells14181426 - 11 Sep 2025
Viewed by 1519
Abstract
Giant pandas (Ailuropoda melanoleuca), a flagship endangered species under priority preservation in China, remain poorly understood in terms of their testicular physiology and the mechanisms underlying spermatogenesis. Testicular peritubular cells (TPTCs), a crucial somatic cell type surrounding seminiferous tubules, secrete growth [...] Read more.
Giant pandas (Ailuropoda melanoleuca), a flagship endangered species under priority preservation in China, remain poorly understood in terms of their testicular physiology and the mechanisms underlying spermatogenesis. Testicular peritubular cells (TPTCs), a crucial somatic cell type surrounding seminiferous tubules, secrete growth factors such as GDNF and CSF1 and release inflammatory factors such as IL-6 and IL-1β, contributing to the testicular niche and immune homeostasis. The contraction of TPTCs also facilitates the transport of sperm towards the epididymis. Nonetheless, TPTCs tend to undergo replicative senescence in vitro, which is a hinderance to their in-depth study. Here, we generated an immortalized monoclonal cell line with TPTC identities from giant pandas via lentiviral transduction of SV40 large T antigen into the cells and the subsequent clonal isolation through limiting dilution. The generated cell line, designated PD-TPTCs, demonstrated unlimited proliferative capacity and has been cultured for over five months and passaged more than 50 times to date. Characterization of PD-TPTCs revealed stable expression of key TPTC markers including ACTA2, MYH11, CNN1, and AR. Moreover, PD-TPTCs could respond to ATP and forskolin (FSK) stimulation with a pro-inflammatory gene expression profile and increased steroidogenic activity, respectively, and they were also amenable to lipofection. As such, the generated PD-TPTC line represents a promising cellular model for future mechanistic studies on the testicular niche, spermatogenesis, and reproductive disorders in giant pandas, laying the foundation for the development of novel assisted reproductive technology (ART) in this endangered species. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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13 pages, 2310 KB  
Article
Protein Kinase A Regulates the Cell Cycle to Affect the Induction Rate in the Parthenogenetic Reproduction of the Silkworm, Bombyx mori
by Fang Xu, Wei Yu, Chenkai Ma, Chengjie Hu, Chunguang Cui, Xin Du, Jine Chen, Linbao Zhu, Shaofang Yu, Xingjian He, Yongqiang Wang and Xia Xu
Cells 2025, 14(11), 793; https://doi.org/10.3390/cells14110793 - 28 May 2025
Cited by 1 | Viewed by 892
Abstract
Protein kinase A (PKA), commonly referred to as cAMP-dependent protein kinase, exists as a heterotetramer composed of two catalytic (C) and regulatory subunits (R). This versatile kinase exhibits regulatory functions in various biological processes including growth, division, and differentiation. Although PKA is well [...] Read more.
Protein kinase A (PKA), commonly referred to as cAMP-dependent protein kinase, exists as a heterotetramer composed of two catalytic (C) and regulatory subunits (R). This versatile kinase exhibits regulatory functions in various biological processes including growth, division, and differentiation. Although PKA is well established as a master regulator of oocyte maturation across species, its functional role in insect parthenogenesis has remained enigmatic. Here, we systematically investigated the regulatory effect of PKA in the induction of parthenogenesis in model lepidopteran Bombyx mori. Our findings demonstrated an inverse correlation between PKA activity and parthenogenetic induction efficiency in silkworms. Notably, PKA activation resulted in delayed embryonic development, whereas PKA-C1 knockdown disrupted normal cell cycle progression. These results indicated that maintaining appropriate PKA activity is essential for ensuring proper cell division process, especially in the successful induction of silkworm parthenogenesis. The evolutionary conservation of PKA across species, coupled with its critical regulatory role in parthenogenesis, positions this kinase as a promising molecular target for breeding design. Our findings establish a foundation for developing silkworm strains with enhanced parthenogenetic capacity through PKA modulation, thereby facilitating the preservation of elite production traits. These results provide novel mechanistic insights into parthenogenesis while demonstrating the potential application of PKA regulation in both genetic studies and breeding programs. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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Review

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24 pages, 456 KB  
Review
Noninvasive Preimplantation Genetic Testing in Recurrent Pregnancy Loss and Implantation Failure: Breakthrough or Overpromise?
by Grzegorz Mrugacz, Aleksandra Mospinek, Joanna Głowacka, Oskar Sprawski, Lidia Kawałek, Wiktoria Gąsior, Julita Machałowska, Yekaterina Sidorova, Patrycja Borecka, Aleksandra Bojanowska and Weronika Szczepańska
Cells 2025, 14(20), 1591; https://doi.org/10.3390/cells14201591 - 14 Oct 2025
Cited by 1 | Viewed by 3518
Abstract
Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, [...] Read more.
Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70–85%, specificity 88–92%) compared to biopsy. Other significant factors include the high rates of amplification failure (10–50%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons. Wider Implications: The integration of niPGT with artificial intelligence, time-lapse imaging, and multi-omics profiling underlies a promising future. However, its transition from a predominantly research tool to a clinical standard necessitates various critical undertakings. These include rigorous multicenter RCTs, standardizing international protocol, and tailoring validation for the RPL and RIF subgroups. This review highlights the need for cautious optimism, positing that evidence-based integration, rather than premature adoption, is essential to realizing niPGT’s full potential without compromising patient care in these complex fertility scenarios. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology: Cellular and Molecular Mechanisms)
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