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Fertilization

Anatomy and Physiology · NLM MeSH · updated 2026-10-31 · version 1

Citations verified against PubMedNot yet clinician-reviewed10 referencesApproximately 3 min read

The fusion of a spermatozoon (spermatozoa) with an OVUM thus resulting in the formation of a zygote.

Table of Contents

1. Definition2. Research landscape3. Reading the evidence4. Open-access studies5. Key reviews6. References7. About this article

Definition and research guide

This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.

Content available: 4 complete abstracts (607 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.

Definition

The fusion of a spermatozoon (spermatozoa) with an OVUM thus resulting in the formation of a zygote.

Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.

Also known as: Fertilizations; Conception; Conceptions; Fertilization, Delayed; Delayed Fertilization; Delayed Fertilizations; Fertilizations, Delayed; Fertilization, Polyspermic.

Where it fits in the MeSH classification

Broader topics
Reproduction
Narrower topics
Ovum Transport; Self-Fertilization; Sperm Capacitation; Sperm-Ovum Interactions; Sperm Transport
See also
Gamete Intrafallopian Transfer; Posthumous Conception

Related concepts

  • Spermatozoa
  • Zygote

Research landscape

PubMed indexes 26,366 records tagged with the MeSH heading “Fertilization” (counts retrieved 2026-10-31). 2,893 of them (11.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 12,495 records.

Reviews account for 3,188 records (12.1%) and meta-analyses for 80. Randomized controlled trials number 232 (0.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.

PubMed records by publication periodthrough 1999: 12,495 records; 2000-2009: 5,516 records; 2010-2019: 5,462 records; 2020 onward: 2,893 records12,495through 19995,5162000-20095,4622010-20192,8932020 onward
Records in PubMed indexed with this heading, by publication period. Real counts from NCBI E-utilities; the final period covers only part of the current year. Volume reflects how much has been published, not how strong the evidence is.
Show the data
PeriodRecords
through 199912,495
2000-20095,516
2010-20195,462
2020 onward2,893
Share of records by publication typeReviews: 12.1 percent; Meta-analyses: 0.3 percent; Randomized controlled trials: 0.9 percentReviews12.1% (3,188)Meta-analyses0.3% (80)Randomized controlled trials0.9% (232)
Share of all PubMed records on this heading that carry each publication type. Types overlap with other records, so the shares do not sum to 100%.
Publication-type chart data
Publication types among 26,366 PubMed records
TypeRecordsShare
Reviews3,18812.1%
Meta-analyses800.3%
Randomized controlled trials2320.9%

Method: PubMed query "Fertilization"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.

Reading the evidence in anatomy and physiology

Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.

Evidence from open-access studies

These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.

Study comparison — selected abstracts, not a systematic review
Study / authorsYearSource label / designEurope PMC citationsLicence / source
The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization
Turathum B, Gao EM, Chian RC
2021Review article
Design not recorded in structured metadata
245cc by
PMID 34571941 · DOI · PMC8470117
The Endometrial Microbiome and Its Impact on Human Conception
Toson B, Simon C, Moreno I
2022Review article
Design not recorded in structured metadata
97cc by
PMID 35008911 · DOI · PMC8745284
TMEM95 is a sperm membrane protein essential for mammalian fertilization
Lamas-Toranzo I, Hamze JG, Bianchi E, Fernández-Fuertes B, Pérez-Cerezales S, Laguna-Barraza R, et al.
2020Research article
Design not recorded in structured metadata
96cc by
PMID 32484434 · DOI · PMC7295574
Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations
Gan S, Gan S, Li Y, Yin L, Yang X, Lou C, et al.
2026Research article
Design not recorded in structured metadata
1cc by
PMID 41618099 · DOI · PMC12988221

The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization [1]

Review article Turathum B, Gao EM, Chian RC · · 2021 · cited 245 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location.
Closing excerpt
Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (165 words)

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34571941 · DOI · PMC8470117

The Endometrial Microbiome and Its Impact on Human Conception [2]

Review article Toson B, Simon C, Moreno I · · 2022 · cited 97 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment.
Closing excerpt
Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (116 words)

Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35008911 · DOI · PMC8745284

TMEM95 is a sperm membrane protein essential for mammalian fertilization [3]

Research article Lamas-Toranzo I, Hamze JG, Bianchi E, Fernández-Fuertes B, Pérez-Cerezales S, Laguna-Barraza R, et al. · · 2020 · cited 96 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
The fusion of gamete membranes during fertilization is an essential process for sexual reproduction.
Closing excerpt
These data demonstrate that TMEM95 is essential for mammalian fertilization.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (132 words)

The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32484434 · DOI · PMC7295574

Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations [4]

Research article Gan S, Gan S, Li Y, Yin L, Yang X, Lou C, et al. · · 2026 · cited 1 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Oocyte activation is essential for successful fertilization and subsequent embryonic development.
Closing excerpt
Collectively, these findings reveal a previously unrecognized molecular mechanism by which HNRNPR mutations cause sperm-borne oocyte activation failure and male infertility, while highlighting targeted therapeutic strategies to restore fertilization.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (194 words)

Oocyte activation is essential for successful fertilization and subsequent embryonic development. However, only a few disease-causing genes have been associated with sperm-derived oocyte activation failure, and the underlying molecular mechanisms and therapeutic approaches remain largely unknown. Here, we identified pathogenic mutations in HNRNPR from three infertile patients whose partners repeatedly failed to achieve transferable embryos despite undergoing both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Remarkably, artificial oocyte activation (AOA, Srcl₂) combined with ICSI successfully restored fertilization. Whole-exome sequencing revealed HNRNPR mutations shared among affected families. To establish causality, we generated a knock-in mouse model, in which males exhibited phenotypes consistent with those observed in patients. Mechanistically, ICSI with sperm from Hnrnpr-mutated mice was unable to induce normal calcium oscillations in oocytes, while spermatozoa from both humans and mice exhibited reduced expression and mislocalization of phospholipase C zeta (PLCζ). Further analyses demonstrated that hnRNPR regulates Plcz1 splicing in an m6A-dependent manner. Beyond Srcl₂ treatment, we also developed NusA-PLCζ to effectively restore oocyte activation. Collectively, these findings reveal a previously unrecognized molecular mechanism by which HNRNPR mutations cause sperm-borne oocyte activation failure and male infertility, while highlighting targeted therapeutic strategies to restore fertilization.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41618099 · DOI · PMC12988221

Key reviews and meta-analyses

The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.

  • Research article Reactive oxygen species as mediators of sperm capacitation and pathological damage [5]
    Aitken RJ · Mol Reprod Dev · 2017 · cited 449 times (Europe PMC)
  • Research article Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization [6]
    Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, et al. · Hum Reprod Update · 2015 · cited 401 times (Europe PMC)
  • Research article Temperature stress and plant sexual reproduction: uncovering the weakest links [7]
    Zinn KE, Tunc-Ozdemir M, Harper JF · J Exp Bot · 2010 · cited 393 times (Europe PMC)
  • Research article Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation [8]
    Machtinger R, Laurent LC, Baccarelli AA · Hum Reprod Update · 2016 · cited 369 times (Europe PMC)
  • Research article Fertilization: a sperm's journey to and interaction with the oocyte [9]
    Ikawa M, Inoue N, Benham AM, Okabe M · J Clin Invest · 2010 · cited 243 times (Europe PMC)
  • Research article Restarting life: fertilization and the transition from meiosis to mitosis [10]
    Clift D, Schuh M · Nat Rev Mol Cell Biol · 2013 · cited 232 times (Europe PMC)

References

  1. Turathum B, Gao EM, Chian RC. The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization. . 2021. PMID 34571941 · DOI · PMC8470117
  2. Toson B, Simon C, Moreno I. The Endometrial Microbiome and Its Impact on Human Conception. . 2022. PMID 35008911 · DOI · PMC8745284
  3. Lamas-Toranzo I, Hamze JG, Bianchi E, Fernández-Fuertes B, Pérez-Cerezales S, Laguna-Barraza R, et al.. TMEM95 is a sperm membrane protein essential for mammalian fertilization. . 2020. PMID 32484434 · DOI · PMC7295574
  4. Gan S, Gan S, Li Y, Yin L, Yang X, Lou C, et al.. Characterization and therapy of fertilization failure in murine and human models with HNRNPR mutations. . 2026. PMID 41618099 · DOI · PMC12988221
  5. Aitken RJ. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol Reprod Dev. 2017. PMID 28749007 · DOI
  6. Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, et al.. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum Reprod Update. 2015. PMID 25744083 · DOI
  7. Zinn KE, Tunc-Ozdemir M, Harper JF. Temperature stress and plant sexual reproduction: uncovering the weakest links. J Exp Bot. 2010. PMID 20351019 · DOI · PMC2917059
  8. Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update. 2016. PMID 26663221 · DOI · PMC4755440
  9. Ikawa M, Inoue N, Benham AM, Okabe M. Fertilization: a sperm's journey to and interaction with the oocyte. J Clin Invest. 2010. PMID 20364096 · DOI · PMC2846064
  10. Clift D, Schuh M. Restarting life: fertilization and the transition from meiosis to mitosis. Nat Rev Mol Cell Biol. 2013. PMID 23942453 · DOI · PMC4021448

About this article

Sources
NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
Verification
Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
Review state
automated source verified; no human expert review has been recorded yet.
Version
1, last updated 2026-10-31.

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All 542 articles in Anatomy and Physiology →

At a glance

26,366
PubMed records on this heading
11%
published since 2020
3,188
review articles
232
randomized trials
10
verified references below

Counts come from PubMed on 2026-10-31; they show how much has been written, not how strong the evidence is.

Related topics See all →

  • Acrosome ReactionAnatomy and Physiology
  • PregnancyAnatomy and Physiology
  • PlacentationAnatomy and Physiology
  • Pregnancy OutcomeAnatomy and Physiology
  • SpermatogenesisMolecular Biology

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