Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones
Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trop...
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MDPI AG
2022-10-01
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author | Viviane C. L. Gomes Ashley K. Woods Kassandra R. Crissman Camille A. Landry Kalie F. Beckers Bryce M. Gilbert Lucas R. Ferro Chin-Chi Liu Erin L. Oberhaus Jenny L. Sones |
author_facet | Viviane C. L. Gomes Ashley K. Woods Kassandra R. Crissman Camille A. Landry Kalie F. Beckers Bryce M. Gilbert Lucas R. Ferro Chin-Chi Liu Erin L. Oberhaus Jenny L. Sones |
author_sort | Viviane C. L. Gomes |
collection | DOAJ |
description | Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated. Herein, we used the preeclamptic-like BPH/5 mouse model to investigate kisspeptin expression and potential upstream regulatory mechanisms in a PE-like syndrome. Expression of the kisspeptin encoding gene, <i>Kiss1</i>, and the 10-amino-acid kisspeptide (Kp-10), are upregulated in the non-pregnant uterus of BPH/5 females during diestrus and in the maternal-fetal interface during embryonic implantation and decidualization. Correspondingly, the dysregulation of molecular pathways downstream to kisspeptins also occurs in this mouse model. BPH/5 females have abnormal sex steroid hormone profiles during early gestation. In this study, the normalization of circulating concentrations of 17β-estradiol (E2) and progesterone (P4) in pregnant BPH/5 females not only mitigated <i>Kiss1</i> upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine <i>Kiss1</i> upregulation occurs pre-pregnancy and persists during early gestation in a PE-like mouse model. Moreover, this study highlights the role of sex steroid hormones in uteroplacental <i>Kiss1</i> dysregulation and the improvement of placentation by normalization of E2, P4 and <i>Kiss1</i>. |
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language | English |
last_indexed | 2024-03-09T15:54:04Z |
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spelling | doaj.art-fc76955eb4454cf69b6c68d467b38fc82023-11-24T17:49:27ZengMDPI AGReproductive Medicine2673-38972022-10-013426327910.3390/reprodmed3040021Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid HormonesViviane C. L. Gomes0Ashley K. Woods1Kassandra R. Crissman2Camille A. Landry3Kalie F. Beckers4Bryce M. Gilbert5Lucas R. Ferro6Chin-Chi Liu7Erin L. Oberhaus8Jenny L. Sones9Department of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USADepartment of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USASchool of Animal Sciences, Louisiana Agricultural Experiment Station, LSU AgCenter, Baton Rouge, LA 70803, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USASchool of Animal Sciences, Louisiana Agricultural Experiment Station, LSU AgCenter, Baton Rouge, LA 70803, USADepartment of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USAInsufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated. Herein, we used the preeclamptic-like BPH/5 mouse model to investigate kisspeptin expression and potential upstream regulatory mechanisms in a PE-like syndrome. Expression of the kisspeptin encoding gene, <i>Kiss1</i>, and the 10-amino-acid kisspeptide (Kp-10), are upregulated in the non-pregnant uterus of BPH/5 females during diestrus and in the maternal-fetal interface during embryonic implantation and decidualization. Correspondingly, the dysregulation of molecular pathways downstream to kisspeptins also occurs in this mouse model. BPH/5 females have abnormal sex steroid hormone profiles during early gestation. In this study, the normalization of circulating concentrations of 17β-estradiol (E2) and progesterone (P4) in pregnant BPH/5 females not only mitigated <i>Kiss1</i> upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine <i>Kiss1</i> upregulation occurs pre-pregnancy and persists during early gestation in a PE-like mouse model. Moreover, this study highlights the role of sex steroid hormones in uteroplacental <i>Kiss1</i> dysregulation and the improvement of placentation by normalization of E2, P4 and <i>Kiss1</i>.https://www.mdpi.com/2673-3897/3/4/21<i>Kiss1/Kiss1r</i><i>GPR54</i>trophoblastestrogenprogesterone |
spellingShingle | Viviane C. L. Gomes Ashley K. Woods Kassandra R. Crissman Camille A. Landry Kalie F. Beckers Bryce M. Gilbert Lucas R. Ferro Chin-Chi Liu Erin L. Oberhaus Jenny L. Sones Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones Reproductive Medicine <i>Kiss1/Kiss1r</i> <i>GPR54</i> trophoblast estrogen progesterone |
title | Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones |
title_full | Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones |
title_fullStr | Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones |
title_full_unstemmed | Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones |
title_short | Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones |
title_sort | kisspeptin is upregulated at the maternal fetal interface of the preeclamptic like bph 5 mouse and normalized after synchronization of sex steroid hormones |
topic | <i>Kiss1/Kiss1r</i> <i>GPR54</i> trophoblast estrogen progesterone |
url | https://www.mdpi.com/2673-3897/3/4/21 |
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