Carbohydrate Chains in Reproductive Health: Impact on Fertility and Pregnancy

Glycans in Fertility

Glycans serve as crucial yet unrecognized elements in life's complex system through their carbohydrate chains which bond to proteins and lipids, playing essential roles in regulating complex human reproductive processes. Fertility depends on the highly precise coordination between cellular activities and molecular reactions. The role of glycans in fertility and pregnancy is undeniable, and with the advancement of glycan profiling and glycoengineering, we are entering a new era of precision reproductive medicine. Whether you're investigating glycosylation in fertility, seeking biomarkers for pregnancy complications, or developing glycan-based therapeutics, Creative Biolabs' comprehensive glycomics solutions provide unparalleled expertise. Explore our glycoprotein analysis services and therapeutic glycoprotein development to accelerate your reproductive research.

Role of Carbohydrate Chains in Sperm Function and Fertilization

Spermatozoa, the intrepid travelers of the reproductive tract, owe much of their functionality to glycosylation. Successful fertilization requires sperm to develop particular glycan patterns throughout their maturation process. Notably, glycosylation in sperm function and fertilization is critical for:

Fig.1 Glycan-binding receptors on the sperm surface.¹

• Sperm Maturation: As sperm transit through the epididymis, they undergo glycosylation changes that enhance their motility and ability to recognize and bind to the oocyte. This process is vital for acquiring fertilization competence.
• Zona Pellucida Binding: The zona pellucida, a glycoprotein-rich matrix surrounding the oocyte, serves as the initial docking site for sperm. Glycan residues on sperm surface proteins interact specifically with zona pellucida glycoproteins, facilitating sperm binding. For instance, ZP3, a key glycoprotein in the zona pellucida, is instrumental in inducing the acrosome reaction, a prerequisite for oocyte penetration.
• Acrosome Reaction: This exocytotic event, triggered upon binding to the zona pellucida, releases enzymes like acrosin that digest the zona matrix, allowing sperm to access the oocyte. Proper glycosylation of acrosomal proteins ensures the efficacy of this process.

High-Throughput Glycan Profiling in Seminal Fluid Analysis

Male fertility assessments often overlook the importance of glycosylation in sperm function. Our high-throughput glycan screening service enables detailed glycoprofiling of seminal plasma, identifying glycan alterations linked to sperm motility and function.

• Lectin Microarrays for Glycan Detection: Our lectin microarray technology allows rapid, high-throughput screening of sperm glycans, identifying fertility-associated glycoforms.
• NMR Spectroscopy for Glycan Structure Analysis: Using nuclear magnetic resonance (NMR) spectroscopy, we offer detailed glycan structure elucidation to reveal how sperm glycosylation impacts fertilization potential.

Fig.2 Lectin microarray profiling of spermatozoa glycans.¹

Glycan-Associated Reproductive Hormones

Glycans in Embryo Development: From Zygote to Blastocyst

The transformation from a single-celled zygote to a multicellular blastocyst ready for implantation is a journey marked by precise glycan-mediated events:

• Cell Division and Differentiation: Glycans on cell surface receptors and adhesion molecules influence cell-cell interactions, guiding the spatial organization of dividing cells. This orchestration ensures the proper formation of the blastocyst's inner cell mass and trophoblast layer.
• Embryo Transport: As the embryo traverses the fallopian tube, glycan interactions with the epithelial lining facilitate its movement toward the uterine cavity. Disruptions in these glycan-mediated processes can impede embryo transport, leading to ectopic pregnancies.

Understanding glycosylation dynamics during embryo implantation is crucial for optimizing IVF success rates and improving pregnancy outcomes.

• Heparan Sulfate Microarray for Implantation Studies: Our heparin sulfate microarray enables detection of glycosylation changes in trophoblast cells, shedding light on maternal-fetal interactions.
• Glycan Sequencing for Placental Research: We utilize glycoprotein structure analysis to map glycan expression patterns in placental tissues, providing insights into glycosylation-driven placental development.
• Custom Glycan Synthesis for Experimental Models: To support reproductive biology research, Creative Biolabs offers custom glycan synthesis, allowing researchers to investigate synthetic glycans in embryo development and implantation.

Placental Glycosylation

The placenta, a transient yet vital organ, is the lifeline between mother and fetus. Its functionality is heavily reliant on glycosylation:

• Trophoblast Invasion: Trophoblast cells, which form the outer layer of the blastocyst, invade the maternal endometrium to establish the placenta. Glycosylation of cell adhesion molecules modulates this invasion, balancing effective implantation with controlled tissue remodeling.
• Immune Modulation: To prevent maternal immune rejection of the fetus, placental glycoproteins express specific glycan patterns that interact with maternal immune cells, promoting tolerance. Aberrant glycosylation can lead to pregnancy complications such as preeclampsia and fetal growth restrictions.

Glycans Affect Maternal-Fetal Interactions

The dialogue between mother and fetus is a glycan-mediated conversation, essential for maintaining pregnancy and ensuring fetal well-being. Trophoblasts, by virtue of their unique glycosylation patterns, play a pivotal role in modulating maternal immune responses:

• Natural Killer (NK) Cell Interaction: Trophoblast glycans engage with NK cell receptors in the decidua, leading to the secretion of cytokines that promote vascular remodeling rather than cytotoxicity. This interaction is crucial for establishing adequate blood flow to the developing fetus.
• Regulatory T Cells (Tregs): Glycan motifs on trophoblasts can induce the expansion of Tregs, which suppress maternal immune activation against fetal antigens, fostering an immune-tolerant environment.

Glycosylation Patterns in Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL) often involves aberrant glycosylation that affects maternal-fetal immune tolerance and endometrial receptivity. Emerging research shows that specific glycan biomarkers in serum, placenta, and endometrial tissues can predict pregnancy complications.

• N-Glycan Profiling for Risk Assessment: Abnormal glycan expression has been linked to recurrent implantation failure. Using our glycan sequencing platform, we can identify specific glycan patterns associated with poor pregnancy outcomes.
• Advanced Carbohydrate Analysis for Pregnancy Biomarkers: To precisely characterize carbohydrate chains in pregnancy, we employ thin layer chromatography (TLC) for carbohydrate analysis and oligosaccharide analysis to detect subtle glycosylation variations.
• Mass Spectrometry-Based Detection: Utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we provide high-resolution glycan profiling for identifying glycan-based pregnancy biomarkers.

Engineering Glycan-Based Therapies for Fertility Enhancement

With glycosylation playing a regulatory role in fertility, Creative Biolabs offers glycoengineering solutions to optimize reproductive health and enhance assisted reproductive technologies (ART).

• Therapeutic Glycoprotein Development: By modifying glycan structures on reproductive hormones and glycoproteins, our therapeutic glycoprotein development services provide customized glycoprotein-based fertility treatments.
• Glycoengineering for Hormonal Regulation: Our glycoengineering services focus on designing glycoproteins with enhanced receptor-binding affinity, improving the effectiveness of reproductive hormone therapies.
• Knockout and Knockin Strategies for Glycan Modulation: To investigate the role of specific glycosylation sites in reproductive processes, we provide knockout and knockin by precision genome editing services, enabling precise gene modifications in reproductive cells.

Advanced glycan analysis technologies allow for high-resolution mapping of glycans involved in fertility and pregnancy. At Creative Biolabs, we offer state-of-the-art glycomics platforms to support reproductive research. For custom glycan profiling, biomarker discovery, or glycoengineering projects, contact Creative Biolabs—your trusted partner in carbohydrate glycobiology research.

Reference

1. Wang, Shuangjie, et al. "Glycosylation on Spermatozoa, a Promise for the Journey to the Oocyte." Modifications in Biomacromolecules. IntechOpen, 2022. Distributed under Open Access license CC BY 3.0, without modification. https://www.intechopen.com/chapters/83260

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