Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones.
Kisspeptin Is Upregulated at the Maternal-Fetal Interface of the Preeclamptic-like BPH/5 Mouse and Normalized after Synchronization of Sex Steroid Hormones.
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DOI：
10.3390/reprodmed3040021
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发表时间：
2022-12
期刊：
影响因子：
--
通讯作者：
Sones JL
中科院分区：
文献类型：
--
作者：
Gomes VCL;Woods AK;Crissman KR;Landry CA;Beckers KF;Gilbert BM;Ferro LR;Liu CC;Oberhaus EL;Sones JL
母体蜕膜中孕体来源的滋养层细胞的侵入不足是早发性先兆子痫（PE）发展的关键事件，PE是与高母体和胎儿发病率和死亡率相关的PE亚型。Kisspeptins是一个以前被证明能抑制滋养层细胞侵袭的肽家族，与早发性PE的发病机制有关。然而，kisspeptin信号传导在该综合征发生过程中的作用尚未阐明。在此，我们使用先兆子痫样BPH/5小鼠模型来研究PE样综合征中kisspeptin的表达和潜在的上游调控机制。kisspeptin编码基因Kiss 1和10-氨基酸kisspeptide（Kp-10）的表达在间情期BPH/5女性的非妊娠子宫中以及胚胎着床和蜕膜化期间的母胎界面中上调。相应地，kisspeptins下游分子通路的失调也发生在该小鼠模型中。BPH/5雌性在妊娠早期具有异常的性类固醇激素谱。在这项研究中，在妊娠BPH/5女性中，17β-雌二醇（E2）和孕酮（P4）的循环浓度正常化不仅减轻了Kiss 1的上调，而且挽救了kisspeptin下游多种分子的表达，并改善了不良的胎儿胎盘结局。这些发现表明，子宫Kiss 1上调发生在妊娠前，并在PE样小鼠模型的妊娠早期持续存在。此外，这项研究强调了性类固醇激素在子宫胎盘Kiss 1失调中的作用，以及通过E2，P4和Kiss 1的正常化来改善胎盘形成。
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, Kiss1, 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 Kiss1 upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine Kiss1 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 Kiss1 dysregulation and the improvement of placentation by normalization of E2, P4 and Kiss1.
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影响因子：
15.3
作者：
Ashkar, A A;Di Santo, J P;Croy, B A
通讯作者：
Croy, B A
影响因子：
5.6
作者：
Gullo G;Etrusco A;Cucinella G;Perino A;Chiantera V;Laganà AS;Tomaiuolo R;Vitagliano A;Giampaolino P;Noventa M;Andrisani A;Buzzaccarini G
通讯作者：
Buzzaccarini G
影响因子：
4.8
作者：
Calder, Michele;Chan, Yee-Ming;Babwah, Andy V.
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Babwah, Andy V.
影响因子：
3.7
作者：
Francis VA;Abera AB;Matjila M;Millar RP;Katz AA
通讯作者：
Katz AA
影响因子：
5.6
作者：
Cavaliere AF;Perelli F;Zaami S;D'Indinosante M;Turrini I;Giusti M;Gullo G;Vizzielli G;Mattei A;Scambia G;Vidiri A;Signore F
通讯作者：
Signore F