Uterine RGS2 expression is regulated by exogenous estrogen and progesterone in ovariectomized mice, and downregulation of RGS2 expression in artificial decidualized ESCs inhibits trophoblast spreading in vitro

Abstract

Embryo implantation is a complicated event that relies on two critical factors: the competent blastocyst and the receptive uterus. Successful implantation results from tight coordination of these two factors. The maternal hormone environment of the uterus and molecular cross‐talk between the embryo and uterine tissue play pivotal roles in implantation. Here we showed that regulator of G‐protein signaling 2 (RGS2), a member of ubiquitous family of proteins that regulate G‐protein activation, plays an important role in embryo implantation by interfering in the cross‐talk between the embryo and uterine tissue. RGS2 expression increased during the implantation process, and was higher in the implant site than at the nonimplantation site. Meanwhile, ovariectomized (OVX) mice exhibited higher expression of RGS2 in the uterus. Exogenous 17β‐estradiol and progesterone in OVX mice downregulated the expression of RGS2. Treatment with exogenous 17β‐estradiol alone caused uterine RGS2 messenger RNA levels of OVX mice to return to those of normal female mice; when these mice were treated with progesterone or 17β‐estradiol plus progesterone, RGS2 levels rose. Downregulation of Rgs2 by small interfering RNA in an in vitro coculture system of decidualized endometrial stromal cells and blastocysts inhibited blastocyst outgrowth by restricting trophoblast spreading, suggesting a mechanism by which RGS2 regulates embryo implantation.

Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare

“…Additional genes with known roles in decidualization and implantation were dual specificity phosphatase 1 ( DUSP1 ), EGR1 , integrin subunit beta 8 ( ITGB8 ), and norrin cystine knot growth factor NDP ( NDP ) 76 – 79 . In agreement with the very late and non-invasive implantation in the mare, many genes known to have negative effects on decidualization and invasive implantation were found as upregulated in LE of pregnant compared to cyclic mares, e.g., parathyroid hormone-hike hormone ( PTHLH ) 80 , regulator of G protein signaling 2 ( RGS2 ) 81 , and tissue inhibitor of metalloproteinases-3 ( TIMP3 ) 82 .…”

Uterine extracellular vesicles as multi-signal messengers during maternal recognition of pregnancy in the mare

“…In the parallel endometrium study, RGS2 was found as upregulated in LE of pregnant compared to cyclic mares at later stages 12 . This gene has been associated with negative effects on decidualization and invasive implantation, linked to the very late and non-invasive implantation in the mare 65 . On the miRNA level, it is noteworthy that 6 out of the 15 DA miRNAs were increased at day 10 compared to the other days p.o.…”

Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal–fetal interface

“…The mice were raised under a 12 h light/dark cycle under specific pathogen-free conditions with 55–65% relative humidity at 22–24°C, and were allowed free access to water and standard rodent chow. Mice were ovariectomized (OVX) under general anesthesia, as described previously [ 38 ], and were kept individually for two weeks for complete recovery. The mice were then regrouped again, and 60 mice were randomly divided into six groups with 10 mice in each group: (1) The E 2 group: OVX mice received daily intraperitoneal (IP) injections of corn oil containing E 2 (100 ng of E 2 in 100 μL of corn oil/mouse, E2758, Sigma-Aldrich, St. Louis, MO, USA) at 8:30 a.m. for 3 days [ 39 ].…”

“…2835, Tocris Bioscience, Bristol, UK) at 8:30 a.m. for 3 consecutive days [ 40 ]. (3) The E 2 + P 4 group: OVX mice received daily IP injection of E 2 (100 ng of E 2 in 100 μL of corn oil/mouse) at 8:30 a.m. for 2 days, and then were treated with P 4 (1 mg of P 4 in 100 μL of corn oil/mouse) by IP injection at 8:30 a.m. on the 3rd day [ 38 ]. (4) The ICI 182780 group: female mice with intact ovaries received IP injection of ICI 182780 (an estrogen receptor antagonist, 100 μg/mouse, Cat.…”