Conditional Ablation of Progesterone Receptor Membrane Component 1 Results in Subfertility in the Female and Development of Endometrial Cysts

McCallum ML, Melissa L. McCallum, Cindy A. Pru, Pru CA, Yuichi Niikura, Niikura Y, Siu-Pok Yee, Yee SP, Siu‐Pok Yee, John P. Lydon, Lydon JP, John J. Peluso, Peluso JJ, James K. Pru, Pru JK
Endocrinology · 2016 · vol. 157(9) , pp. 3309–3319 · doi:10.1210/en.2016-1081 · PMID:27309940 · PMC5007897 · W2443102477
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Conditional ablation of progesterone receptor membrane component 1 in female mice resulted in subfertility and the development of endometrial cysts, demonstrating its importance in fertility and uterine homeostasis.

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Abstract

Progesterone (P4) is essential for female fertility. The objective of this study was to evaluate the functional requirement of the nonclassical P4 receptor (PGR), PGR membrane component 1, in regulating female fertility. To achieve this goal, the Pgrmc1 gene was floxed by insertion of loxP sites on each side of exon 2. Pgrmc1 floxed (Pgrmc1(fl/fl)) mice were crossed with Pgr(cre) or Amhr2(cre) mice to delete Pgrmc1 (Pgrmc1(d/d)) from the female reproductive tract. A 6-month breeding trial revealed that conditional ablation of Pgrmc1 with Pgr(cre/+) mice resulted in a 40% reduction (P = .0002) in the number of pups/litter. Neither the capacity to ovulate in response to gonadotropin treatment nor the expression of PGR and the estrogen receptor was altered in the uteri of Pgrmc1(d/d) mice compared with Pgrmc1(fl/fl) control mice. Although conditional ablation of Pgrmc1 from mesenchymal tissue using Amhr2(cre/+) mice did not reduce the number of pups/litter, the total number of litters born in the 6-month breeding trial was significantly decreased (P = .041). In addition to subfertility, conditional ablation of Pgrmc1 using either Amhr2(cre/+) or Pgr(cre/+) mice resulted in the development of endometrial cysts starting around 4 months of age. Interestingly, pregnancy attenuated the formation of these uterine cysts. These new findings demonstrate that PGR membrane component 1 plays an important role in female fertility and uterine tissue homeostasis.

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MeSH descriptors

Endometrium Fertility Membrane Proteins Receptors, Progesterone Animals Cysts Cysts Endometrium Estrogen Receptor alpha Estrogen Receptor alpha Female Gene Silencing Membrane Proteins Mice, Inbred C57BL Random Allocation Receptors, Progesterone Receptors, Progesterone

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