Conditional Ablation of Progesterone Receptor Membrane Component 1 Results in Subfertility in the Female and Development of Endometrial Cysts.
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.
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
Melissa L
ML
McCallum
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
Cindy A
CA
Pru
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
Yuichi
Y
Niikura
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
Siu-Pok
SP
Yee
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
John P
JP
Lydon
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
John J
JJ
Peluso
Department of Animal Sciences (M.L.M., C.A.P., Y.N., J.K.P.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164; Departments of Cell Biology and Obstetrics and Gynecology (S.P.Y., J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030; and Department of Molecular and Cellular Biology (J.P.L.), Baylor College of Medicine, Houston, Texas 77030.
James K
JK
Pru
D000818:Animals; D003560:Cysts / Q000209:etiology; D004717:Endometrium / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005298:Fertility; D020868:Gene Silencing; D008565:Membrane Proteins / Q000502:physiology*; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D011980:Receptors, Progesterone / Q000378:metabolism / Q000502:physiology*
D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; C508868:PGRMC1 protein, mouse; D011980:Receptors, Progesterone