PUBLICATION

Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish

Authors
Wu, X.J., Jermaul Williams, M., Rameshkumar Patel, P., Ann Kew, K., Zhu, Y.
ID
ZDB-PUB-190714-8
Date
2019
Source
General and comparative endocrinology   282: 113218 (Journal)
Registered Authors
Zhu, Yong
Keywords
DHP, Pgrmc2, oocyte maturation, progestin, steroid synthesis, subfertility
MeSH Terms
  • Animals
  • Base Sequence
  • Female
  • Gene Expression Regulation
  • Infertility/genetics
  • Infertility/metabolism*
  • Infertility/pathology*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Mutation/genetics
  • Oocytes/metabolism
  • Oogenesis
  • Ovarian Follicle/metabolism
  • Progestins/biosynthesis*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Progesterone/genetics
  • Receptors, Progesterone/metabolism*
  • Reproduction/genetics
  • Sexual Maturation
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
31301284 Full text @ Gen. Comp. Endocrinol.
Abstract
Progestin receptor membrane component (Pgrmc1 & 2) is a heme-binding protein. Studies on Pgrmc1 have suggested possible roles in heme binding, activation of steroid-synthesizing P450s, along with binding and transferring of membrane proteins. However, the studies of Pgrmc1's paralog, Pgrmc2 are still lacking. In order to determine the physiologic function(s) of Pgrmc2, we generated a zebrafish mutant line (pgrmc2-/-). We found a reduction in both spawning frequency and the number of embryos produced in female pgrmc2-/-. This subfertility is caused by reduced oocyte maturation (germinal vesicle breakdown, GVBD) in pgrmc2-/- in vivo. Nonetheless, oocytes from pgrmc2-/- had similar sensitivity to 17α,20β-dihydroxy-4-pregnen-3-one (DHP, a maturation induced progestin in zebrafish) compared with wildtype (wt) in vitro. Therefore, we hypothesized that oocyte maturation tardiness found in vivo, could be due to lack of progestin in pgrmc2-/-. Interestingly, we found significant reduced expression of hormones, receptors, and steroid synthesizing enzymes including lhcgr, egfra, ar, and esr2, cyp11a1 and hsd3b1. In addition, DHP levels in pgrmc2-/- ovaries showed a significant decrease compared to those in wt. In summary, we have provided a plausible molecular mechanism for the physiological functions of Pgrmc2 in the regulation of female fertility, likely via regulation of receptors and steroids in the ovary, which in turn regulates oocyte maturation in zebrafish.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes