Bone morphogenetic protein 15

Source: Wikipedia, the free encyclopedia.
BMP15
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000130385

ENSMUSG00000023279

UniProt

O95972

Q9Z0L4

RefSeq (mRNA)

NM_005448

NM_009757

RefSeq (protein)

NP_005439

NP_033887

Location (UCSC)Chr X: 50.91 – 50.92 MbChr X: 6.23 – 6.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Bone morphogenetic protein 15 (BMP-15) is a

pre-ovulatory follicles
.

Structure & Interactions

Structure

The BMP-15

disulphide bonds and the seventh being involved in the formation of dimers with other monomers.[7] BMP-15 is an exception to this as the molecule does not contain the seventh cysteine.[7] Instead in BMP-15 the fourth cysteine is replaced by a serine.[7]

Interactions

BMP-15 and

dimerization.[9] However, in the BMP-15 the homodimers form as a non-covalent bond is present between two BMP-15 subunits.[7]

Function

Functions of BMP-15 include[10]

Folliculogenesis

Folliculogenesis is an important process for the development and maintenance of

preovulatory follicles ready for ovulation, when the oocyte is released into the fallopian tube of the female reproductive tract.[11]

BMP-15 main functions are crucial for the beginning of folliculogenesis as seen in Image 1. The primordial follicle is made up of the oocyte and a single layer of flattened granulosa cells. BMP-15 is released from the oocyte into the surrounding granulosa tissue where it binds to two membrane bound receptors on granulosa cells.

luteinization, subsequently granulosa cells do not differentiate.[12][8]

As BMP-15 acts directly on granulosa cells it has an important influence on granulosa function including

steroidogenesis inhibition of luteinization and differentiation of cumulus, without which would lead to infertility and lack of folliculogenesis.[13]

Differences between species

The use of mammalian species other than human is often used in research to learn more about human biology.

Sheep

Two breeds of sheep,

streak ovaries and the primary stage of folliculogenesis is inhibited.[9] These studies suggest that BMP-15 plays a vital role in the normal regulation of folliculogenesis and ovulation in sheep.[12]

Mice

In mice, the BMP-15

heterozygotes.[9] The homozygous mutant mice did not suffer from reduced folliculogenesis or impacted follicle progression, unlike in the sheep homologue knockout experiments.[9] The subfertility seen in the homozygous mutant phenotype was attributed to defective ovulation and reduced viability of embryos. Here it can be stated that BMP-15 is not as vital for normal female mouse fertility as it is for sheep.[9]

Humans

Humans display a similar

primary amenorrhea, showing that BMP-15 is also vital to normal human female fertility, concordant with the sheep model.[9]

Current theory

The main theory for this stark difference between mammalian species relates to the number of follicles normally ovulated in each cycle by each species.[9] Humans and sheep are mono-ovulatory, potentially explaining the difference in litter size observed in mutant individuals.[9] As mice are poly-ovulatory, the role of BMP-15 in female mouse fertility may not be as obvious.[9]

Clinical relevance

premature ovarian failure and other reproductive pathologies.[13]

BMP-15 defects have been implicated in female sterility, Polycystic Ovary Syndrome (PCOS), primary ovarian insufficiency (POI) and endometriosis. Women with PCOS have been noted to have higher levels of BMP-15,[8] while missense mutations of the protein have been identified in females with POI.[9]

Research has also found inherited mutant BMP-15 to be involved with the pathogenesis of hypergonadotropic ovarian failure.[8] This condition develops due to BMP-15 role in folliculogenesis, and the errors that occur when a mutant gene is inherited. The protein is linked to familial ovarian dysgenesis which results in hypergonadotropic ovarian failure.[8]

The importance of BMP-15 in ovulation and folliculogenesis has been highlighted by research into Turner syndrome, a chromosomal abnormality where females are missing a complete or partial X chromosome. Depending on the chromosomal mutation, BMP-15 gene dosage varies and impacts ovarian development in Turner syndrome patients. The gene is thus involved in determining the extent of the ovarian defects present in Turner syndrome.[9]

BMP-15 is also present in animals and involved in reproduction, such as in mice and sheep. Reduced levels of BMP-15 in sheep have shown to increase ovulation, leading to larger litter sizes.[9] 

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130385 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023279 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
    PMID 15454632
    .
  6. ^
    PMID 30039232
    .
  7. ^
    PMID 20959140
    .
  8. ^
    PMID 15136966
    .
  9. ^
    PMID 24980253
    .
  10. PMID 24980253
    .
  11. OCLC 1120337244
    .
  12. ^
    S2CID 6500889
    .
  13. ^
    PMID 26954112
    .

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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