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Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish.
Gen Comp Endocrinol 2019; 282:113218GC

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.

Authors+Show Affiliations

Department of Biology, East Carolina University, Greenville, NC 27858, USA.Department of Biology, East Carolina University, Greenville, NC 27858, USA.Department of Biology, East Carolina University, Greenville, NC 27858, USA.Department of Chemistry, 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

Language

eng

PubMed ID

31301284

Citation

Wu, Xin-Jun, et al. "Subfertility and Reduced Progestin Synthesis in Pgrmc2 Knockout Zebrafish." General and Comparative Endocrinology, vol. 282, 2019, p. 113218.
Wu XJ, Williams MJ, Patel PR, et al. Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish. Gen Comp Endocrinol. 2019;282:113218.
Wu, X. J., Williams, M. J., Patel, P. R., Kew, K. A., & Zhu, Y. (2019). Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish. General and Comparative Endocrinology, 282, p. 113218. doi:10.1016/j.ygcen.2019.113218.
Wu XJ, et al. Subfertility and Reduced Progestin Synthesis in Pgrmc2 Knockout Zebrafish. Gen Comp Endocrinol. 2019 Jul 10;282:113218. PubMed PMID: 31301284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish. AU - Wu,Xin-Jun, AU - Williams,Marcus Jermaul, AU - Patel,Pujan Rameshkumar, AU - Kew,Kimberly Ann, AU - Zhu,Yong, Y1 - 2019/07/10/ PY - 2019/03/10/received PY - 2019/06/14/revised PY - 2019/07/06/accepted PY - 2019/7/14/pubmed PY - 2019/7/14/medline PY - 2019/7/14/entrez KW - DHP KW - Oocyte maturation KW - Pgrmc2 KW - Progestin KW - Steroid synthesis KW - Subfertility SP - 113218 EP - 113218 JF - General and comparative endocrinology JO - Gen. Comp. Endocrinol. VL - 282 N2 - 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. SN - 1095-6840 UR - https://www.unboundmedicine.com/medline/citation/31301284/Subfertility_and_reduced_progestin_synthesis_in_Pgrmc2_knockout_zebrafish L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(19)30126-1 DB - PRIME DP - Unbound Medicine ER -