Zona pellucida

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Introduction

Oocyte and developing zona pellucida in the ovary
Oocyte and developing zona pellucida in the ovary
Human blastocyst "hatching" from the zona pellucida
Human blastocyst "hatching" from the zona pellucida (week 1 Carnegie stage 3)


(Latin, zona pellucida = transparent zone) The zona pellucida (ZP) is a specialized extracellular matrix surrounding the developing oocyte (egg, ovum) within each follicle within the ovary. This thick matrix is thought to be formed by secretions from the oocyte and the follicle granulosa cells and in human oocytes consists of four types of zona pellucida glycoproteins ZP1, ZP2, ZP3 and ZP4 which have different roles in fertilization. Note that mice also have 4 ZP genes, but multiple stop and missense codons in ZP4 means that only three are produced. Polymers of ZP2 and ZP3 organized into extended filaments that are cross-linked by ZP1 homodimers.


Note that depending upon species and type of study, the zona pellucida can also be called the: oolemma, egg coat or vitelline membrane.


The zona pellucid has many different roles including in oocyte development, protection during growth and transport, fertilization, spermatozoa binding, preventing polyspermy, blastocyst development, and preventing premature implantation (ectopic pregnancy).

Human oocyte 11.jpg Early zygote.jpg
Human oocyte contained inside zona pellucida.[1] Early zygote inside zona pellucida

In human development, during the first week of development following fertilization the zona pellucida remains surrounding the blastocyst from which it "hatches" to commence implantation.


Fertilization Links: fertilization | oocyte | spermatozoa | meiosis | menstrual cycle | zona pellucida | zygote | granulosa cell Lecture - Fertilization | 2016 Lecture | mitosis | Lecture - Week 1 and 2 | hydatidiform mole | Assisted Reproductive Technology | | morula | blastocyst | Lecture - Genital Development | Category:Fertilization
Historic Embryology  
1910 Fertilization | 1919 Human Ovum | 1921 The Ovum | 1927 First polar body | 1929 Oocyte Size | 1943 Fertilization | 1944 In vitro fertilization | 1948 In vitro fertilization


Some Recent Findings

Human zygote inside the zone pellucida
Mouse germinal vesicle
Mouse germinal vesicle[2]
  • Perivitelline threads in cleavage-stage human embryos: observations using time-lapse imaging[3] "Time-lapse imaging of the human preimplantation embryo in vitro has revealed a transient phenomenon involving the appearance of perivitelline threads, commonly observed at the two-cell stage. These threads span the perivitelline space, arising at the specific area where the cytoplasmic membrane contacts the zona pellucida, before any perivitelline space is formed. The threads persist as the cytoplasmic membrane retracts from the zona pellucida to form the first cleavage furrow. In this observational report, these structures and their incidence are described. ...Presence or absence of threads did not affect embryo development. This descriptive study is limited; further characterization of these structures is needed to elucidate their potential role in early human embryo development."
  • A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans[4] "The extracellular zona pellucida surrounds ovulated eggs and mediates gamete recognition that is essential for mammalian fertilization. Zonae matrices contain three (mouse) or four (human) glycoproteins (ZP1-4), but which protein binds sperm remains controversial. ...These observations in transgenic mice document that the ZP2(51-149) sperm-binding domain is necessary for human and mouse gamete recognition and penetration through the zona pellucida."
  • Biosynthesis of hamster zona pellucida is restricted to the oocyte[4] "In the present work, the expression of ZP1, ZP2, ZP3 and ZP4 is carefully analyzed by in situ hybridization (ISH) in hamster ovaries. Our data suggest that the four hamster ZP genes are expressed in a coordinate and oocyte-specific manner during folliculogenesis. Furthermore, this expression is maximal during the first stages of the oocyte development and declines in oocytes from later development stages, particularly within large antral follicles."
  • Zona pellucida birefringence in in vivo and in vitro matured oocytes[5]
  • Zona pellucida glycoprotein-1 binds to spermatozoa and induces acrosomal exocytosis[6] "These studies revealed for the first time that in humans ZP1, in addition to ZP3 and ZP4, binds to capacitated spermatozoa and induces acrosomal exocytosis."
More recent papers  
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Zona pellucida Development

Yulong Han, Cheng Peng, Le Wang, Jiani Guo, Mingwei Lu, Jiaxin Chen, Yun Liu, Shuisheng Li, Mi Zhao, Yong Zhang, Haoran Lin Female-to-male sex reversal in orange-spotted grouper (Epinephelus coioides) caused by over-expressing of Amh in vivo. Biol. Reprod.: 2018; PubMed 30010724

Manouchehr Safari, Houman Parsaie, Hamid Reza Sameni, Mohammad Reza Aldaghi, Sam Zarbakhsh Anti-Oxidative and Anti-Apoptotic Effects of Apigenin on Number of Viable and Apoptotic Blastomeres, Zona Pellucida Thickness and Hatching Rate of Mouse Embryos. Int J Fertil Steril: 2018, 12(3);257-262 PubMed 29935073

Stephen Frankenberg, Marilyn B Renfree Conceptus Coats of Marsupials and Monotremes. Curr. Top. Dev. Biol.: 2018, 130;357-377 PubMed 29853183

Shunsuke Nishio, Hiroki Okumura, Tsukasa Matsuda Egg-Coat and Zona Pellucida Proteins of Chicken as a Typical Species of Aves. Curr. Top. Dev. Biol.: 2018, 130;307-329 PubMed 29853181

Nathalie Jiatsa Donfack, Kele Amaral Alves, Benner Geraldo Alves, Rebeca Magalhães Pedrosa Rocha, Jamily Bezzera Bruno, Marcelo Bertolini, Regiane Rodrigues Dos Santos, Sheyla Farhaydes Souza Domingues, José Ricardo De Figueiredo, Johan Smitz, Ana Paula Ribeiro Rodrigues Stroma cell-derived factor 1 and connexins (37 and 43) are preserved after vitrification and in vitro culture of goat ovarian cortex. Theriogenology: 2018, 116;83-88 PubMed 29783047

Three-dimensional Structure

Mouse zona pellucida[7]

Electron microscopic studies have shown a variety of appearances from a porous, net-like structure to a nearly smooth and compact structure.

An scanning electron microscopic review[8] of both human and mouse zona pellucida structures at ovulation show:

  • spongy ZP appearance well correlates with mature oocytes.
  • a delicate meshwork of thin interconnected filaments
  • a regular alternating pattern of wide and tight meshes.
  • wide meshes correspond to "pores" of the "spongy" ZP.
    • tight meshes correspond to the compact parts of the ZP surrounding the pores.


Human Zona Pellucida

An immunochemistry study[9] of human ZP proteins expression during folliculogenesis within the ovary primordial follicle identified the presence of ZP1 and ZP3 in most follicles (93% and 95%, respectively), with ZP2 only in 32% of these follicles. The ZP proteins were also detected in the cytoplasm of cuboidal granulosa cells. This localization suggested to the authors that these proteins had been present since oogenesis.

Human embryo day 5 label.gif

Mouse Zona Pellucida

Mouse zona pellucida

Mouse zona pellucida development.[7]


In the mouse ovarian oocytes, and not granulosa cells, are the only source for mouse ZP glycoproteins.<[10]

Zona Pellucida Glycoprotein Features

Human oocyte contained inside zona pellucida
Human oocyte contained inside zona pellucida.[1]
  1. A "ZP domain", which is a signature domain comprised of approximately 260 amino acid (aa) residues.
  2. An N-terminal hydrophobic signal peptide sequence.
  3. A potential N- and O-linked glycosylation sites.
  4. A C-terminal hydrophobic transmembrane-like domain (TMD)
  5. A potential consensus proprotein convertase (furin) cleavage site (CFCS) upstream of transmembrane-like domain (TMD).

Zona Pellucida glycoprotein 1

(ZP1) A 638 amino acid glycoprotein located in the zona pellucida, synthesized by and surrounding the oocyte.

Links: OMIM - ZP1

Zona Pellucida glycoprotein 2

Model of gamete recognition zona pellucida
Model of gamete recognition zona pellucida[11]

(ZP2) A 745 amino acid glycoprotein located in the zona pellucida, synthesized by and surrounding the oocyte. The protein acts as a secondary sperm receptor that binds sperm only after the induction of the sperm acrosome reaction. Before fertilization ZP2 binds spermatozoa. After fertilization ZP2 is proteolytically cleaved as an initial block to polyspermy.

Links: OMIM - ZP2

Zona Pellucida glycoprotein 3

Zona Pellucida Glycoprotein 3 (ZP3) A 424 amino acid glycoprotein located in the zona pellucida, synthesized by and surrounding the oocyte required for initial zona matrix formation and during fertilization for species-specific sperm binding. Now thought to exist in 2 isoforms ZP3A and ZP3B (a second polymorphic allele).


A study using the mouse oocyte,{{#pmid28145526|PMID28145526}} has shown that ZP3 is also required for germinal vesicle breakdown in oocyte meiosis. ZP3 was initially expressed in the nucleus during prophase, and then translocates to the zona pellucida. Several potential ZP3-interacting proteins for the germinal vesicle effect were identified in this study: Protein tyrosine phosphatase, receptor type K (Ptprk), Aryl hydrocarbon receptor-interacting protein-like 1 (Aipl1), and Diaphanous related formin 2 (Diaph2).


Links: OMIM - ZP3

Zona Pellucida glycoprotein 4

(ZP4) A 540 amino acid glycoprotein located in the zona pellucida, synthesized by and surrounding the oocyte required for initial zona matrix formation and along with ZP3 during fertilization for inducing the acrosome reaction and inhibited the binding of spermatozoa to zona pellucida in a time- and dose-dependent reaction. Associated with several mammalian species (human, rat, hamster and rabbit) but not all mammalian species.

Links: OMIM - ZP4

Zona Pellucida Binding Protein

(ZPBP) Not a zona pellucida protein, but a spermatozoa protein found located on the acrosome surface and one of several proteins that participate in secondary binding between acrosome-reacted sperm and the zona pellucida.

Links: OMIM - ZPBP

Zona Pellucida Birefringence

(ZPB) Optical property of the zona pellucida using polarization imaging when viewed microscopically. This property has been used to qualitatively predict the developmental potential of a in vitro matured metaphase-II (MII) oocytes.

High birefringence, compared to low, has been associated with oocytes contributing to conception cycles when compared with those of nonconception cycles and higher implantation, pregnancy, and live birth rates from transferred oocytes.[12][5] This work follows on from the earlier discovery of an increased birefringence in the meiotic spindle an early indicator of oocyte activation[13]

Oocyte zona birefringence intensity is associated with embryonic implantation potential in ICSI cycles[12]

"Using zona birefringence as the only selection criterion, two fertilized oocytes, preferably derived from high birefringence (HZB) oocytes, were selected for further culture and transfer. The required criteria were met by 135 ICSI cycles (124 patients; 34.9 ± 4.1 years of age). Embryos for transfer were used in 20 cycles derived from HZB/HZB oocytes, in 50 cycles from HZB/LZB oocytes and in 65 from LZB/LZB oocytes. The corresponding implantation (P < 0.025), pregnancy (P < 0.005) and live birth (P < 0.025) rates were significantly different between HZB/HZB and HZB/LZB versus LZB/LZB group. Embryo development was superior in embryos derived from HZB oocytes."

Zona pellucida birefringence in in vivo and in vitro matured oocytes[5]

The percentage of high birefringence oocytes was higher in immature than in mature oocytes (40.1 vs. 23.6%). Among immature oocytes, an increased percentage of HB in prophase-I stage oocytes compared to metaphase I stage oocytes was also observed (50.7 vs. 25.0%). However, the percentage of HB oocytes did not change when comparing oocytes before and after in vitro maturation for both prophase I and metaphase I oocytes. No influence of ZPB was observed on the spontaneous in vitro maturation potential. Exclusively for metaphase II retrieved oocytes, a positive influence of ZPB on fertilization (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.27-2.49) and embryo quality (OR, 2.28; 95% CI, 1.04-4.99) was noted.


Birefringence - Defined as the double refraction of light in a transparent, molecularly ordered material, which is manifested by the existence of orientation-dependent differences in refractive index.


Links: Olympus - Optical Birefringence

Abnormalities

Empty Follicle Syndrome

Empty Follicle Syndrome (EFS) is clinically defined as the failure to aspirate oocytes from mature ovarian follicles during in vitro fertilization. At least one genetic cause has been identified, a missense mutation in zona pellucida protein 3 (ZP3).[14]

Zona Pellucida Antibodies

The zona pellucida has been shown to contain tissue-specific and species-specific antigens that can generate antibodies that inhibit sperm attachment. Anti-zona pellucida antibodies have been shown to occur in human serum though the cause of their generation is largely unknown.[15] It has been suggested that this may be a contributing factor to infertility[16] and premature ovarian failure.[17]


Note the generation of zona pellucida antibodies from specific antigens has also been used in controlling animal fertility.[18] This has also been suggested as a possible target in generating a contraceptive vaccine for controlling human fertility.[18]


Terms

  • acrosome reaction - The chemical change within the spermatozoa following binding to the zona pellucida, that leads to the release of acrosomal enzymatic contents. These enzymes degrade the zona pellucida and allow a spermatozoa to penetrate an oocyte.

References

  1. 1.0 1.1 Shi W, Xu B, Wu LM, Jin RT, Luan HB, Luo LH, Zhu Q, Johansson L, Liu YS & Tong XH. (2014). Oocytes with a dark zona pellucida demonstrate lower fertilization, implantation and clinical pregnancy rates in IVF/ICSI cycles. PLoS ONE , 9, e89409. PMID: 24586757 DOI.
  2. Zhou HX, Ma YZ, Liu YL, Chen Y, Zhou CJ, Wu SN, Shen JP & Liang CG. (2014). Assessment of mouse germinal vesicle stage oocyte quality by evaluating the cumulus layer, zona pellucida, and perivitelline space. PLoS ONE , 9, e105812. PMID: 25144310 DOI.
  3. Kellam L, Pastorelli LM, Bastida AM, Senkbeil A, Montgomery S, Fishel S & Campbell A. (2017). Perivitelline threads in cleavage-stage human embryos: observations using time-lapse imaging. Reprod. Biomed. Online , 35, 646-656. PMID: 29074360 DOI.
  4. 4.0 4.1 Izquierdo-Rico MJ, Gimeno L, Jiménez-Cervantes C, Ballesta J & Avilés M. (2011). Biosynthesis of hamster zona pellucida is restricted to the oocyte. Theriogenology , 75, 463-72. PMID: 21074836 DOI.
  5. 5.0 5.1 5.2 de Almeida Ferreira Braga DP, de Cássia Savio Figueira R, Queiroz P, Madaschi C, Iaconelli A & Borges E. (2010). Zona pellucida birefringence in in vivo and in vitro matured oocytes. Fertil. Steril. , 94, 2050-3. PMID: 20079896 DOI.
  6. Ganguly A, Bukovsky A, Sharma RK, Bansal P, Bhandari B & Gupta SK. (2010). In humans, zona pellucida glycoprotein-1 binds to spermatozoa and induces acrosomal exocytosis. Hum. Reprod. , 25, 1643-56. PMID: 20504872 DOI.
  7. 7.0 7.1 Wassarman PM. (2008). Zona pellucida glycoproteins. J. Biol. Chem. , 283, 24285-9. PMID: 18539589 DOI.
  8. Familiari G, Relucenti M, Heyn R, Micara G & Correr S. (2006). Three-dimensional structure of the zona pellucida at ovulation. Microsc. Res. Tech. , 69, 415-26. PMID: 16703610 DOI.
  9. Gook DA, Edgar DH, Borg J & Martic M. (2008). Detection of zona pellucida proteins during human folliculogenesis. Hum. Reprod. , 23, 394-402. PMID: 18033806 DOI.
  10. El-Mestrah M, Castle PE, Borossa G & Kan FW. (2002). Subcellular distribution of ZP1, ZP2, and ZP3 glycoproteins during folliculogenesis and demonstration of their topographical disposition within the zona matrix of mouse ovarian oocytes. Biol. Reprod. , 66, 866-76. PMID: 11906903
  11. Avella MA, Baibakov B & Dean J. (2014). A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans. J. Cell Biol. , 205, 801-9. PMID: 24934154 DOI.
  12. 12.0 12.1 Montag M, Schimming T, Köster M, Zhou C, Dorn C, Rösing B, van der Ven H & Ven der Ven K. (2008). Oocyte zona birefringence intensity is associated with embryonic implantation potential in ICSI cycles. Reprod. Biomed. Online , 16, 239-44. PMID: 18284880
  13. Liu L, Trimarchi JR, Oldenbourg R & Keefe DL. (2000). Increased birefringence in the meiotic spindle provides a new marker for the onset of activation in living oocytes. Biol. Reprod. , 63, 251-8. PMID: 10859266
  14. Chen T, Bian Y, Liu X, Zhao S, Wu K, Yan L, Li M, Yang Z, Liu H, Zhao H & Chen ZJ. (2017). A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility. Am. J. Hum. Genet. , 101, 459-465. PMID: 28886344 DOI.
  15. Caudle MR & Shivers CA. (1989). Current status of anti-zona pellucida antibodies. Am. J. Reprod. Immunol. , 21, 57-60. PMID: 2697213
  16. Koyama K, Hasegawa A, Mochida N & Calongos G. (2005). Follicular dysfunction induced by autoimmunity to zona pellucida. Reprod Biol , 5, 269-78. PMID: 16372044
  17. Takamizawa S, Shibahara H, Shibayama T & Suzuki M. (2007). Detection of antizona pellucida antibodies in the sera from premature ovarian failure patients by a highly specific test. Fertil. Steril. , 88, 925-32. PMID: 17349637 DOI.
  18. 18.0 18.1 Naz RK, Gupta SK, Gupta JC, Vyas HK & Talwar AG. (2005). Recent advances in contraceptive vaccine development: a mini-review. Hum. Reprod. , 20, 3271-83. PMID: 16113040 DOI.


Reviews

Nishio S, Okumura H & Matsuda T. (2018). Egg-Coat and Zona Pellucida Proteins of Chicken as a Typical Species of Aves. Curr. Top. Dev. Biol. , 130, 307-329. PMID: 29853181 DOI.

Hasegawa A, Tanaka H & Shibahara H. (2014). Infertility and Immunocontraception based on zona pellucida. Reprod. Med. Biol. , 13, 1-9. PMID: 29699147 DOI.

Gupta SK. (2015). Role of zona pellucida glycoproteins during fertilization in humans. J. Reprod. Immunol. , 108, 90-7. PMID: 25445843 DOI.

Wassarman PM. (2008). Zona pellucida glycoproteins. J. Biol. Chem. , 283, 24285-9. PMID: 18539589 DOI.

Articles

Hirohashi N & Yanagimachi R. (2018). Sperm acrosome reaction: Its site and role in fertilization. Biol. Reprod. , , . PMID: 29462288 DOI.

Liu W, Bai D, Chen J & Gao S. (2017). Additive-effect pattern of both ZP2 and ZP3 in human and mouse. Hum. Genet. , 136, 1493-1495. PMID: 29094202 DOI.

Liu W, Li K, Bai D, Yin J, Tang Y, Chi F, Zhang L, Wang Y, Pan J, Liang S, Guo Y, Ruan J, Kou X, Zhao Y, Wang H, Chen J, Teng X & Gao S. (2017). Dosage effects of ZP2 and ZP3 heterozygous mutations cause human infertility. Hum. Genet. , 136, 975-985. PMID: 28646452 DOI.

Chen T, Bian Y, Liu X, Zhao S, Wu K, Yan L, Li M, Yang Z, Liu H, Zhao H & Chen ZJ. (2017). A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility. Am. J. Hum. Genet. , 101, 459-465. PMID: 28886344 DOI.

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Cite this page: Hill, M.A. (2018, July 20) Embryology Zona pellucida. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Zona_pellucida

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