Cracking the egg: increased complexity in the zona pellucida

Conner, Sarah J.; Lefièvre, Linda; Hughes, David C.; Barratt, Christopher L.R.

doi:10.1093/humrep/deh835

Cited by 120 publications

(82 citation statements)

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“…11 Its functions include recognizing gametes, supporting oocyte-follicle cell communication, and protecting the oocyte. [12][13][14] To explore the relationship between ZP3 and EFS, we first conducted immunofluorescence analysis of ZP3 localization in the degenerated oocytes of the proband of family A (III-10). Oocytes of the proband and normal control were labeled with anti-ZP3 (Proteintech) and anti-actin (Sigma-Aldrich) antibodies.…”

Section: Efs Can Be Classified As Either False Efs (Fefs) or Genuine mentioning

confidence: 99%

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility

Chen

Bian

Liu

et al. 2017

The American Journal of Human Genetics

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Empty follicle syndrome (EFS) is defined as the failure to aspirate oocytes from mature ovarian follicles during in vitro fertilization. Except for some cases caused by pharmacological or iatrogenic problems, the etiology of EFS remains enigmatic. In the present study, we describe a large family with a dominant inheritance pattern of female infertility characterized by recurrent EFS. Genome-wide linkage analyses and whole-exome sequencing revealed a paternally transmitted heterozygous missense mutation of c.400 G>A (p.Ala134Thr) in zona pellucida glycoprotein 3 (ZP3). The same mutation was identified in an unrelated EFS pedigree. Haplotype analysis revealed that the disease allele of these two families came from different origins. Furthermore, in a cohort of 21 cases of EFS, two were also found to have the ZP3 c.400 G>A mutation. Immunofluorescence and histological analysis indicated that the oocytes of the EFS female had degenerated and lacked the zona pellucida (ZP). ZP3 is a major component of the ZP filament. When mutant ZP3 was co-expressed with wild-type ZP3, the interaction between wild-type ZP3 and ZP2 was markedly decreased as a result of the binding of wild-type ZP3 and mutant ZP3, via dominant negative inhibition. As a result, the assembly of ZP was impeded and the communication between cumulus cells and the oocyte was prevented, resulting in oocyte degeneration. These results identified a genetic basis for EFS and oocyte degeneration and, moreover, might pave the way for genetic diagnosis of infertile females with this phenotype.During in vitro fertilization (IVF) treatment, oocyte retrieval is performed after ovarian stimulation via vaginal puncture. Cumulus-oocyte complexes (COCs), which consist of cumulus cells surrounding the centrally located oocyte, are isolated from the individual's follicular fluid. As was first described by Coulam et al. in 1986, empty follicle syndrome (EFS) is a condition in which the ovarian response to stimulation and follicular development seems normal but no oocytes are retrieved for fertilization.1 EFS can be classified as either false EFS (FEFS) or genuine EFS (GEFS). FEFS is mainly caused by pharmacological or iatrogenic problems; however, the etiology of GEFS, which is responsible for about 33% of EFS, still remains enigmatic. 2 It has been proposed that GEFS is caused by dysfunctional folliculogenesis, ovarian aging, or genetic factors including pericentric inversion of chromosome 2 and LHCGR (MIM: 152790) mutations. 3-7 A retrospective study of 12,359 individuals who underwent assisted reproductive technology (ART) revealed that the prevalence of GEFS was about 0.016%. 8 Without oocytes for fertilization, these individuals fail to achieve pregnancy after a demanding and expensive medical intervention, resulting in stress to both physicians and the individuals themselves.9

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Section: Efs Can Be Classified As Either False Efs (Fefs) or Genuine mentioning

confidence: 99%

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility

Chen

Bian

Liu

et al. 2017

The American Journal of Human Genetics

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“…These egg envelopes are mainly constructed of glycoproteins belonging to different subclasses of the ZP gene family (Spargo & Hope 2003, Conner et al 2005, Smith et al 2005. The components of this matrix include three glycoproteins (i.e., ZP1, ZP2, and ZP3, which are also known as ZPB1, ZPA, and ZPC respectively, according to Spargo & Hope (2003) and Smith et al (2005)) in most mammalian species (Harris et al 1994) and four glycoproteins in several organisms including humans, bonnet monkeys, and rats (ZP1, ZP2, ZP3, and ZP4 (ZPB2); Lefievre et al 2004, Hoodbhoy et al 2005, Ganguly et al 2008, while non-mammalian vertebrates such as amphibians (i.e., Xenopus laevis and X. tropicalis), five ZP glycoproteins (ZP2, ZP3, ZP4, ZPD, and ZPAX) have been identified (Lindsay et al 2003, Goudet et al 2008.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of egg envelope glycoprotein ZPD in the ovary of Japanese quail (Coturnix japonica)

Sato

Kinoshita²,

Kansaku³

et al. 2009

Reproduction

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The egg envelope surrounding avian oocytes exhibits a three-dimensional network of coarse fibers between the granulosa cells and the oocyte. Our previous studies have demonstrated that one of the matrix's components, ZP3, is synthesized in the ovarian granulosa cells. Another component, ZP1, which is critically involved in triggering the sperm acrosome reaction, is synthesized in the liver. We have previously isolated cDNAs encoding quail ZP3 and ZP1, and we now report the isolation of cDNA encoding quail ZPD. By RNase protection assay and in situ hybridization, we have demonstrated that ZPD transcripts are restricted to the granulosa cells of preovulatory follicles. The expression level of ZPD increased progressively during follicular development, and the highest expression was observed in the largest follicles. Western blot analyses using the specific antibody against ZPD indicate that the 40 kDa protein is the authentic ZPD, and the contents of ZPD protein also increased during follicular development. Moreover, we found that the addition of FSH to the culture media enhances the ZPD secretion in the cultured granulosa cells. Two-dimensional gel electrophoresis revealed the presence of several ZPD isoforms with different pI values ranging from 5.5 to 7. Immunohistochemical analyses indicate that the materials recognized with anti-quail ZPD antibody were accumulated in the egg envelope of large yellow follicles. These results demonstrate the presence of ZPD protein in the egg envelope, and that the amount of ZPD in the egg envelope as well as the mRNA in the cells increases at the latter stages of folliculogenesis.

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“…For example, the predominant model of mouse egg coat (zona pellucida) formation posits filaments of arrays of two ZP proteins (ZP2 and ZP3) crosslinked via a third (ZP1), resulting in a fibrous matrix completely enclosing the egg (1). Although orthologs of these mammalian proteins are known from egg coat structures across vertebrate lineages (6,7), non-vertebrate taxa are less well studied and it is not yet clear whether ZP proteins are similarly prominent features of egg coats across metazoans. For example, all known proteins comprising Drosophila egg coat structures lack ZP domains (8).…”

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confidence: 99%

Rapidly evolving zona pellucida domain proteins are a major component of the vitelline envelope of abalone eggs

Aagaard

MacCoss

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

116

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Proteins harboring a zona pellucida (ZP) domain are prominent components of vertebrate egg coats. Although less well characterized, the egg coat of the non-vertebrate marine gastropod abalone (Haliotis spp.) is also known to contain a ZP domain protein, raising the possibility of a common molecular basis of metazoan egg coat structures. Egg coat proteins from vertebrate as well as non-vertebrate taxa have been shown to evolve under positive selection. Studied most extensively in the abalone system, coevolution between adaptively diverging egg coat and sperm proteins may contribute to the rapid development of reproductive isolation. Thus, identifying the pattern of evolution among egg coat proteins is important in understanding the role these genes may play in the speciation process. The purpose of the present study is to characterize the constituent proteins of the egg coat [vitelline envelope (VE)] of abalone eggs and to provide preliminary evidence regarding how selection has acted on VE proteins during abalone evolution. A proteomic approach is used to match tandem mass spectra of peptides from purified VE proteins with abalone ovary EST sequences, identifying 9 of 10 ZP domain proteins as components of the VE. Maximum likelihood models of codon evolution suggest positive selection has acted among a subset of amino acids for 6 of these genes. This work provides further evidence of the prominence of ZP proteins as constituents of the egg coat, as well as the prominent role of positive selection in diversification of these reproductive proteins.adaptive evolution ͉ egg coat proteins ͉ gamete recognition M etazoan eggs are surrounded by a fibrous coat referred to as the zona pellucida, as the vitelline or perivitelline envelope, or as the chorion. The constituent proteins of these structures, which we collectively refer to as egg coats, have been well characterized among vertebrate taxa, including species of mammals (1), teleost fish (2), amphibians (3), and birds (4). These studies show the principle constituents of vertebrate egg coats to be glycosylated proteins sharing a common structural motif of Ϸ260 aa known as the zona pellucida (ZP) domain. ZP domain proteins are found among diverse eukaryotic structures, facilitating protein polymerization through intramolecular disulfide bonds among conserved cysteine resides within the ZP domain (5). For example, the predominant model of mouse egg coat (zona pellucida) formation posits filaments of arrays of two ZP proteins (ZP2 and ZP3) crosslinked via a third (ZP1), resulting in a fibrous matrix completely enclosing the egg (1). Although orthologs of these mammalian proteins are known from egg coat structures across vertebrate lineages (6, 7), non-vertebrate taxa are less well studied and it is not yet clear whether ZP proteins are similarly prominent features of egg coats across metazoans. For example, all known proteins comprising Drosophila egg coat structures lack ZP domains (8). However, a large glycoprotein from the egg coat [vitelline envelope (VE)] of the m...

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Cracking the egg: increased complexity in the zona pellucida

Cited by 120 publications

References 23 publications

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility

Molecular characterization of egg envelope glycoprotein ZPD in the ovary of Japanese quail (Coturnix japonica)

Rapidly evolving zona pellucida domain proteins are a major component of the vitelline envelope of abalone eggs

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