STRA8

STRA8
Identifiers
Aliases	STRA8 , stimulated by retinoic acid 8
External IDs	OMIM: 609987; MGI: 107917; HomoloGene: 49197; GeneCards: STRA8; OMA:STRA8 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q33 Start 135,231,979 bp [1] End 135,258,663 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 B1 Start 34,897,098 bp [2] End 34,916,279 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad sural nerve human kidney placenta right testis renal cortex left testis skin of abdomen left uterine tube putamen Top expressed in spermatogonium seminiferous tubule blastocyst spermatid trophoblast giant cell embryo morula spermatocyte embryo greater petrosal nerve More reference expression data BioGPS n/a
Gene ontology Molecular function protein dimerization activity Cellular component cytoplasm nucleus Biological process DNA replication cellular response to retinoic acid meiosis spermatogenesis regulation of transcription, DNA-templated male germ-line stem cell asymmetric division transcription, DNA-templated positive regulation of transcription by RNA polymerase II oogenesis cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 346673 20899 Ensembl ENSG00000146857 ENSMUSG00000029848 UniProt Q7Z7C7 P70278 RefSeq (mRNA) NM_182489 NM_001394401 NM_009292 RefSeq (protein) NP_872295 NP_033318 Location (UCSC) Chr 7: 135.23 – 135.26 Mb Chr 6: 34.9 – 34.92 Mb PubMed search [3] [4]
Wikidata
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Stimulated by retinoic acid 8 is a protein that in humans is encoded by the STRA8 gene.

STRA8 is activated only upon stimulation by retinoic acid and expresses a cytoplasmic protein in the gonads of male and female vertebrates. ^[5] It plays a key role in gametogenesis by inducing meiosis.

Structure

The Stra8 gene is 26,749 base pairs in length and the Stra8 protein is 36.9 kDa or 330 amino acids. Its protein structure contains a series of alpha helices.

Function

Stra8 functions to initiate the transition between mitosis and meiosis. It does so by forming a complex with the protein MEIOSIN, also initiated by the presence of retinoic acid, to transcribe genes responsible for meiotic activation. ^[6] Both males and females are left infertile if Stra8 signaling is absent due to spermatogenesis and oogenesis remaining uninitiated. ^[7]

Activation by retinoic acid

As implied by its full name, Stra8 is induced by the presence of retinoic acid. The promoter for Stra8 contains a retinoic acid responsive element that induces expression of the Stra8 gene. ^[8] During fetal development, retinoic acid is supplied from the mesonephros. ^[9]

Role in spermatogenesis

Male expression of Stra8 is limited by CYP26B1 activity from fetal to prepubescent development, thus matching the need of spermatogenesis beginning at puberty compared to embryonic oogenesis in females. ^[7] Following prepubescence, CYP26B1 is no longer expressed, preventing the degradation of retinoic acid and allowing Stra8 to fulfill its function and initiate spermatogenesis. The mechanisms behind the gradual decrease in CYP26B1 expression remains to be elucidated.

Sperm of mice that had induced null mutations for the Stra8 gene were able to undergo mitotic divisions, and while some sperm were able to transition into the early stages of meiosis I, they could not transition into further sub-stages. Errors in chromosome pairing and chromosome condensation were observed following these failures. ^[10]

Role in oogenesis

Female expression of Stra8 is uninhibited by CYP26B1 in the primordial germ cells, initiating meiosis. ^[11] This process may also be referred to as oocytogenesis. The primary oocytes formed will then become arrested in meiosis (prophase I) until menarche.

In female mice, loss of Stra8 signaling shows failure to enter into meiosis. ^[12]

Clinical significance

Induction by cosmetics/medications

Products that contain retinoic acid (alternatively retinol or vitamin A) have the potential to cause severe birth defects when used during pregnancy. ^[13] Induction of Stra8 by retinoic acid can result in premature cell differentiation in the embryo.

Products that contain retinoic acid should be avoided during pregnancy.

References

1. GRCh38: Ensembl release 89: ENSG00000146857 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029848 – 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. Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AM, et al. (September 2008). "Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice". Proceedings of the National Academy of Sciences of the United States of America. 105 (39): 14976–14980. Bibcode:2008PNAS..10514976A. doi: 10.1073/pnas.0807297105 . PMC   2542382 . PMID   18799751.
6. Ishiguro KI, Matsuura K, Tani N, Takeda N, Usuki S, Yamane M, et al. (February 2020). "MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells". Developmental Cell. 52 (4): 429–445.e10. doi: 10.1016/j.devcel.2020.01.010 . PMID   32032549.
7. Zhou Q, Nie R, Li Y, Friel P, Mitchell D, Hess RA, et al. (July 2008). "Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal murine testes". Biology of Reproduction. 79 (1): 35–42. doi:10.1095/biolreprod.107.066795. PMC   3208264 . PMID   18322276.
8. Ma HT, Niu CM, Xia J, Shen XY, Xia MM, Hu YQ, et al. (2018). "Stimulated by retinoic acid gene 8 (Stra8) plays important roles in many stages of spermatogenesis". Asian Journal of Andrology. 20 (5): 479–487. doi: 10.4103/aja.aja_26_18 . PMC   6116687 . PMID   29848833.
9. Spiller CM, Bowles J, Koopman P (2012). "Regulation of germ cell meiosis in the fetal ovary". The International Journal of Developmental Biology. 56 (10–12): 779–787. doi:10.1387/ijdb.120142pk. PMID   23417400.
10. Mark M, Jacobs H, Oulad-Abdelghani M, Dennefeld C, Féret B, Vernet N, et al. (October 2008). "STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation". Journal of Cell Science. 121 (Pt 19): 3233–3242. doi: 10.1242/jcs.035071 . PMID   18799790.
11. Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AM, et al. (September 2008). "Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice". Proceedings of the National Academy of Sciences of the United States of America. 105 (39): 14976–14980. Bibcode:2008PNAS..10514976A. doi: 10.1073/pnas.0807297105 . PMC   2542382 . PMID   18799751.
12. Baltus AE, Menke DB, Hu YC, Goodheart ML, Carpenter AE, de Rooij DG, et al. (December 2006). "In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication". Nature Genetics. 38 (12): 1430–1434. doi:10.1038/ng1919. PMID   17115059. S2CID   17258424.
13. Pennimpede T, Cameron DA, MacLean GA, Li H, Abu-Abed S, Petkovich M (October 2010). "The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis". Birth Defects Research. Part A, Clinical and Molecular Teratology. 88 (10): 883–894. doi:10.1002/bdra.20709. PMID   20842651.