Evidence map›Paper›PMID 28498971›Full record

ArticleEndocrinology2017

Deletion of RhoA in Progesterone Receptor-Expressing Cells Leads to Luteal Insufficiency and Infertility in Female Mice.

Ahmed E El Zowalaty, Rong Li, Yi Zheng, John P Lydon, Francesco J DeMayo, Xiaoqin Ye

Open access · hybridAbstract read
In one paragraph

Article in Endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Functions of RhoA in the female reproductive system.Reproductive and developmental medicine · 2025
    Review
  3. Article
  4. Reproductive and developmental medicine · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Effects of PInternational journal of molecular sciences · 2021
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Reply to Liu et al.: ALK5-mediated tumor suppressor signaling through SMAD2 and SMAD3 in the uterus.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  19. Article
  20. Multidrug Resistance Protein 1 Deficiency Promotes Doxorubicin-Induced Ovarian Toxicity in Female Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Ahmed E El ZowalatyDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602.
Rong LiDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602.
Yi ZhengDivision of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
John P LydonDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030.
Francesco J DeMayoReproductive and Developmental Biology Laboratory/Pregnancy and Female Reproduction Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Xiaoqin YeDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602.
University of Georgia · USBaylor College of Medicine · USCincinnati Children's Hospital Medical Center · USNational Institute of Environmental Health Sciences · US

Funding

Environmental Signaling in Reproduction and PregnancyZIAES103311 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DEMAYO, FRANCESCO · 2016 to 2025
$30.5M
Testosterone-GnRH Frequency and the Evolution of PCOS in AdolescenceP50HD028934 · NICHD · UNIVERSITY OF VIRGINIA · PI HAISENLEDER, DANIEL J. · 2014 to 2018
$8.6M
Molecular mechanism of LPA3-mediated uterine receptivityR01HD065939 · NICHD · UNIVERSITY OF GEORGIA · PI YE, XIAOQIN · 2011 to 2015
$1.5M
Luminal epithelial microenvironment in Lpar3(-/-) peri-implantation uterusR15HD066301 · NICHD · UNIVERSITY OF GEORGIA · PI YE, XIAOQIN · 2010 to 2010
$371k
NICHD NIH HHS P50 HD028934NICHD NIH HHS R01 HD065939NICHD NIH HHS R15 HD066301
6 · The paper itself

Abstract

Ras homolog gene family, member A (RhoA) is widely expressed throughout the female reproductive system. To assess its role in progesterone receptor-expressing cells, we generated RhoA conditional knockout mice RhoAd/d (RhoAf/f-Pgr-Cre+/-). RhoAd/d female mice had comparable mating activity, serum luteinizing hormone, prolactin, and estradiol levels and ovulation with control but were infertile with progesterone insufficiency, indicating impaired steroidogenesis in RhoAd/d corpus luteum (CL). RhoA was highly expressed in wild-type luteal cells and conditionally deleted in RhoAd/d CL. Gestation day 3.5 (D3.5) RhoAd/d ovaries had reduced numbers of CL, less defined corpus luteal cord formation, and disorganized CL collagen IV staining. RhoAd/d CL had lipid droplet and free cholesterol accumulation, indicating the availability of cholesterol for steroidogenesis, but disorganized β-actin and vimentin staining, indicating disrupted cytoskeleton integrity. Cytoskeleton is important for cytoplasmic cholesterol movement to mitochondria and for regulating mitochondria. Dramatically reduced expression of mitochondrial markers heat shock protein 60 (HSP60), voltage-dependent anion channel, and StAR was detected in RhoAd/d CL. StAR carries out the rate-limiting step of steroidogenesis. StAR messenger RNA expression was reduced in RU486-treated D3.5 wild-type CL and tended to be induced in progesterone-treated D3.5 RhoAd/d CL, with parallel changes of HSP60 expression. These data demonstrated the in vivo function of RhoA in CL luteal cell cytoskeleton integrity, cholesterol transport, StAR expression, and progesterone synthesis, and a positive feedback on StAR expression in CL by progesterone signaling. These findings provide insights into mechanisms of progesterone insufficiency.

Indexed as

AnimalsCorpus LuteumCorpus Luteum MaintenanceFemaleGene DeletionInfertility, FemaleLuteal CellsMaleMiceMice, KnockoutOvaryPregnancyProgesteroneReceptors, ProgesteronerhoA GTP-Binding ProteinProgesteroneReceptors, ProgesteronerhoA GTP-Binding Protein

Identifiers

PMID28498971
PMCPMC5505209
OpenAlexW2613406075

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.