Journal article
Conditional Ablation of Progesterone Receptor Membrane Component 2 Causes Female Premature Reproductive Senescence
Endocrinology (Philadelphia), Vol.158(3), pp.640-651
03/01/2017
Handle:
https://hdl.handle.net/2376/103277
PMCID: PMC5460782
PMID: 28005395
Abstract
The nonclassical progesterone receptors progesterone receptor membrane component (PGRMC) 1 and PGRMC2 have been implicated in regulating cell survival of endometrial and ovarian cells in vitro and are abundantly expressed in these cell types. The objective of this study was to determine if Pgrmc1 and Pgrmc2 are essential for normal female reproduction. To accomplish this objective, Pgrmc1 and/or Pgrmc2 floxed mice (Pgrmc2fl/fl and Pgrmc1/2fl/fl) were crossed with Pgr-cre mice, which resulted in the conditional ablation of Pgrmc1 and/or Pgrmc2 from female reproductive tissues (i.e.,Pgrmc2d/d and Pgrmc1/2d/d mice). A breeding trial revealed that conditional ablation of Pgrmc2 initially led to subfertility, with Pgrmc2d/d female mice producing 47% fewer pups/litter than Pgrmc2fl/fl mice (P = 0.001). Pgrmc2d/d mice subsequently underwent premature reproductive senescence by parities 2 to 5, producing 37.8% fewer litters overall during the trial compared with Pgrmc2fl/fl mice (P = 0.020). Similar results were observed with Pgrmc1/2d/d mice. Based on ovarian morphology and serum P4, the subfertility/infertility was not due to faulty ovulation or luteal insufficiency. Rather an analysis of midgestation implantation sites revealed that postimplantation embryonic death was the major cause of the subfertility/infertility. As with our previous report of Pgrmc1d/d mice, Pgrmc2d/d and Pgrmc1/2d/d mice developed endometrial cysts consistent with accelerated aging of this tissue. Given the timing of postimplantation embryonic demise, uterine decidualization may be disrupted in mice deficient in PGRMC2 or PGRMC1/2. Overall, this study revealed that Pgrmc1 and/or Pgrmc2 are required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan.
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Details
- Title
- Conditional Ablation of Progesterone Receptor Membrane Component 2 Causes Female Premature Reproductive Senescence
- Creators
- Nicole C Clark - Department of Animal Sciences, Center for Reproductive Biology, Washington State University, Pullman, WashingtonCindy A Pru - Department of Animal Sciences, Center for Reproductive Biology, Washington State University, Pullman, WashingtonSiu-Pok Yee - Departments of Cell Biology and Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, ConnecticutJohn P Lydon - Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TexasJohn J Peluso - Departments of Cell Biology and Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, ConnecticutJames K Pru - Department of Animal Sciences, Center for Reproductive Biology, Washington State University, Pullman, Washington
- Publication Details
- Endocrinology (Philadelphia), Vol.158(3), pp.640-651
- Academic Unit
- Animal Sciences, Department of
- Publisher
- United States
- Grant note
- P50 HD028934 / NICHD NIH HHS U54 HD028934 / NICHD NIH HHS R21 RR030264 / NCRR NIH HHS R21 OD016564 / NIH HHS P30 HD028934 / NICHD NIH HHS
- Identifiers
- 99900546699701842
- Language
- English
- Resource Type
- Journal article