Stra8 Explained

Stra8
Symbol:STRA8
Hgncid:30653
Omim:609987
Uniprot:Q7Z7C7
Chromosome:7
Arm:q
Band:33
Refseq (Mrna):NM_001394401.1
Refseq (Protein):NP_001381330.1

Stimulated by retinoic acid 8 (Stra8) is a gene coding for a protein of the same name that is activated only upon stimulation by retinoic acid and expresses a cytoplasmic protein in the gonads of male and female vertebrates.[1] 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.[2] Both males and females are left infertile if Stra8 signaling is absent due to spermatogenesis and oogenesis remaining uninitiated.

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.[3] During fetal development, retinoic acid is supplied from the mesonephros.[4]

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.[5] 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.[6]

Role in Oogenesis

Female expression of Stra8 is uninhibited by CYP26B1 in the primordial germ cells, initiating meiosis.[7] 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.[8]

Clinical Significance

Induction by Retinoic Acid in Cosmetics/Medications

Products that contain retinoic acid (alternatively retinol or vitamin A) have the potential to cause severe birth defects when used during pregnancy.[9] Induction of Stra8 by retinoic acid can result in premature cell differentiation in the embryo.

References

  1. Page. David C.. Pelt. Ans M. M. van. Rooij. Dirk G. de. Hassold. Terry J.. Roepers-Gajadien. Hermien L.. Baltus. Andrew E.. Anderson. Ericka L.. 2008-09-30. Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proceedings of the National Academy of Sciences. en. 105. 39. 14976–14980. 10.1073/pnas.0807297105. 0027-8424. 18799751. 2542382. 2008PNAS..10514976A. free .
  2. Ishiguro . Kei-ichiro . Matsuura . Kumi . Tani . Naoki . Takeda . Naoki . Usuki . Shingo . Yamane . Mariko . Sugimoto . Michihiko . Fujimura . Sayoko . Hosokawa . Mihoko . Chuma . Shinichiro . Ko . Minoru S. H. . Araki . Kimi . Niwa . Hitoshi . 2020-02-24 . MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells . Developmental Cell . English . 52 . 4 . 429–445.e10 . 10.1016/j.devcel.2020.01.010 . 1534-5807 . 32032549. free .
  3. Ma . Hai-Tao . Niu . Chang-Min . Xia . Jing . Sheng . Xue-Yi . Xia . Meng-Meng . Hu . Yan-Qiu . Zheng . Ying . Stimulated by retinoic acid gene 8 (Stra8) plays important roles in many stages of spermatogenesis . Asian Journal of Andrology . 2018 . 20 . 5 . 479–487. 10.4103/aja.aja_26_18 . free . 29848833 . 6116687 .
  4. Spiller . Cassy M. . Bowles . Josephine . Koopman . Peter . 2012 . Regulation of germ cell meiosis in the fetal ovary . The International Journal of Developmental Biology . en . 56 . 10–11–12 . 779–787 . 10.1387/ijdb.120142pk . 23417400 . 0214-6282.
  5. Griswold . Michael D. . Small . Christopher . Hess . Rex A. . Mitchell . Debra . Friel . Patrick . Li . Ying . Nie . Rong . Zhou . Qing . 2008-07-01 . 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 . en . 79 . 1 . 35–42 . 10.1095/biolreprod.107.066795 . 0006-3363 . 3208264 . 18322276.
  6. Ghyselinck . Norbert B. . Chambon . Pierre . Codreanu . Carmen-Alina . Vernet . Nadège . Féret . Betty . Dennefeld . Christine . Oulad-Abdelghani . Mustapha . Jacobs . Hugues . Mark . Manuel . 2008-10-01 . STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation . Journal of Cell Science . en . 121 . 19 . 3233–3242 . 10.1242/jcs.035071 . 0021-9533 . 18799790 . free.
  7. Anderson . Ericka L. . Baltus . Andrew E. . Roepers-Gajadien . Hermien L. . Hassold . Terry J. . de Rooij . Dirk G. . van Pelt . Ans M. M. . Page . David C. . 2008-09-30 . Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice . Proceedings of the National Academy of Sciences . en . 105 . 39 . 14976–14980 . 10.1073/pnas.0807297105 . free . 0027-8424 . 2542382 . 18799751. 2008PNAS..10514976A .
  8. Page . David C. . Rooij . Dirk G. de . Carpenter . Anne E. . Goodheart . Mary L. . Hu . Yueh-Chiang . Menke . Douglas B. . Baltus . Andrew E. . 2006-11-19 . In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication . Nature Genetics . en . 38 . 12 . 1430–1434 . 10.1038/ng1919 . 1546-1718 . 17115059 . 17258424.
  9. Pennimpede . Tracie . Cameron . Don A. . MacLean . Glenn A. . Li . Hui . Abu-Abed . Suzan . Petkovich . Martin . October 2010 . The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis . Birth Defects Research Part A: Clinical and Molecular Teratology . en . 88 . 10 . 883–894 . 10.1002/bdra.20709 . 20842651 . 1542-0752.

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