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Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish.
Gen Comp Endocrinol. 2020 01 01; 285:113275.GC

Abstract

The progestin receptor membrane components (Pgrmcs) contain two paralogs, Pgrmc1 and Pgrmc2. Our previous research into single knockout of Pgrmc1 or Pgrmc2 suggests that Pgrmc1 and Pgrmc2 regulate membrane progestin receptor or steroid synthesis and therefore female fertility in zebrafish. Additional roles of Pgrmcs may not be determined in using single Pgrmc knockouts due to compensatory roles between Pgrmc1 and Pgrmc2. To address this question, we crossed single knockout pgrmc1 (pgrmc1-/-) with pgrmc2 (pgrmc2-/-), and generated double knockouts for both pgrmc1 and pgrmc2 (pgrmc1/2-/-) in a vertebrate model, zebrafish. In addition to the delayed oocyte maturation and reduced female fertility, significant reduced ovulation was found in double knockout (pgrmc1/2-/-) in vivo, though not detected in either single knockout of Pgrmc (pgrmc1-/- or pgrmc2-/-). We also found significant down regulation of nuclear progestin receptor (Pgr) protein expression only in pgrmc1/2-/-, which was most likely the cause of reduced ovulation. Lower protein expression of Pgr also resulted in reduced expression of metalloproteinase in pgrmc1/2-/-. With this study, we have provided new evidence for the physiological functions of Pgrmcs in the regulation of female fertility by regulation of ovulation, likely via regulation of Pgr, which affects regulation of metalloproteinase expression and oocyte ovulation.

Authors+Show Affiliations

Department of Biology, East Carolina University, Greenville, NC 27858, USA.Department of Biology, East Carolina University, Greenville, NC 27858, USA. Electronic address: zhuy@ecu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31536721

Citation

Wu, Xin-Jun, and Yong Zhu. "Downregulation of Nuclear Progestin Receptor (Pgr) and Subfertility in Double Knockouts of Progestin Receptor Membrane Component 1 (pgrmc1) and Pgrmc2 in Zebrafish." General and Comparative Endocrinology, vol. 285, 2020, p. 113275.
Wu XJ, Zhu Y. Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish. Gen Comp Endocrinol. 2020;285:113275.
Wu, X. J., & Zhu, Y. (2020). Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish. General and Comparative Endocrinology, 285, 113275. https://doi.org/10.1016/j.ygcen.2019.113275
Wu XJ, Zhu Y. Downregulation of Nuclear Progestin Receptor (Pgr) and Subfertility in Double Knockouts of Progestin Receptor Membrane Component 1 (pgrmc1) and Pgrmc2 in Zebrafish. Gen Comp Endocrinol. 2020 01 1;285:113275. PubMed PMID: 31536721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of nuclear progestin receptor (Pgr) and subfertility in double knockouts of progestin receptor membrane component 1 (pgrmc1) and pgrmc2 in zebrafish. AU - Wu,Xin-Jun, AU - Zhu,Yong, Y1 - 2019/09/16/ PY - 2019/07/22/received PY - 2019/09/01/revised PY - 2019/09/14/accepted PY - 2021/01/01/pmc-release PY - 2019/9/20/pubmed PY - 2020/3/17/medline PY - 2019/9/20/entrez KW - Metalloproteinase KW - Ovulation KW - Pgr KW - Pgrmc1 KW - Pgrmc2 KW - Progestins SP - 113275 EP - 113275 JF - General and comparative endocrinology JO - Gen. Comp. Endocrinol. VL - 285 N2 - The progestin receptor membrane components (Pgrmcs) contain two paralogs, Pgrmc1 and Pgrmc2. Our previous research into single knockout of Pgrmc1 or Pgrmc2 suggests that Pgrmc1 and Pgrmc2 regulate membrane progestin receptor or steroid synthesis and therefore female fertility in zebrafish. Additional roles of Pgrmcs may not be determined in using single Pgrmc knockouts due to compensatory roles between Pgrmc1 and Pgrmc2. To address this question, we crossed single knockout pgrmc1 (pgrmc1-/-) with pgrmc2 (pgrmc2-/-), and generated double knockouts for both pgrmc1 and pgrmc2 (pgrmc1/2-/-) in a vertebrate model, zebrafish. In addition to the delayed oocyte maturation and reduced female fertility, significant reduced ovulation was found in double knockout (pgrmc1/2-/-) in vivo, though not detected in either single knockout of Pgrmc (pgrmc1-/- or pgrmc2-/-). We also found significant down regulation of nuclear progestin receptor (Pgr) protein expression only in pgrmc1/2-/-, which was most likely the cause of reduced ovulation. Lower protein expression of Pgr also resulted in reduced expression of metalloproteinase in pgrmc1/2-/-. With this study, we have provided new evidence for the physiological functions of Pgrmcs in the regulation of female fertility by regulation of ovulation, likely via regulation of Pgr, which affects regulation of metalloproteinase expression and oocyte ovulation. SN - 1095-6840 UR - https://www.unboundmedicine.com/medline/citation/31536721/Downregulation_of_nuclear_progestin_receptor__Pgr__and_subfertility_in_double_knockouts_of_progestin_receptor_membrane_component_1__pgrmc1__and_pgrmc2_in_zebrafish_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(19)30379-X DB - PRIME DP - Unbound Medicine ER -