-
[show abstract]
[hide abstract]
ABSTRACT: Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm. It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy. To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0.002, 4, 10 and 40 ppm ZEA, and 0.05 ppm diethylstilbestrol (DES, positive control) in phytoestrogen-free AIN-93G diet. Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening. Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity. At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating. Treatment resumed upon identification of a vaginal plug on gestation day 0.5 (D0.5). Embryo implantation was assessed on D4.5. Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4.5 uterine epithelium. To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning~mating) and postmating (D0.5~D4.5), respectively. Premating exposure to 40 ppm ZEA diet reduced fertilization rate while postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation. These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events.
Toxicological Sciences 01/2013; · 4.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PRSS23 and PRSS35 are homologous proteases originally identified in mouse ovaries. In the periimplantation mouse uterus, was highly expressed in the preimplantation gestation day 3.5 (D3.5) uterine luminal epithelium (LE). It disappeared from the postimplantation LE and reappeared in the stromal compartment next to the myometrium on D6.5. It was undetectable in the embryo from D4.5 to D6.5 but highly expressed in the embryo on D7.5. became detectable in the uterine stromal compartment surrounding the embryo on D4.5 and shifted towards the mesometrial side of the stromal compartment next to the embryo from D5.5 to D7.5. In the ovariectomized uterus, was moderately and was dramatically downregulated by progesterone and 17β-estradiol. Based on the expression of in granulosa cells and corpus luteum of the ovary and the early pregnant uterus, we hypothesized that PRSS35 might play a role in female reproduction, especially in oocyte development, ovulation, implantation, and decidualization. This hypothesis was tested in mice, which proved otherwise. Between wild type (WT) and mice, superovulation of immature females produced comparable numbers of cumulus-oocyte complexes; there were comparable numbers of implantation sites detected on D4.5 and D7.5; there were no obvious differences in the expression of implantation and decidualization marker genes in D4.5 or D7.5 uteri. Comparable mRNA expression levels of a few known protease-related genes in the WT and D4.5 uteri indicated no compensatory upregulation. Comparable litter sizes from WT × WT and × crosses suggested that gene was unessential for fertility and embryo development. gene has been linked to cleft lip/palate in humans. However, no obvious such defects were observed in mice. This study demonstrates the distinct expression of and in the periimplantation uterus and the dispensable role of in fertility and embryo development.
PLoS ONE 01/2013; 8(2):e56757. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine cyclooxygenase-derived prostanoid signaling in alleviating embryo crowding in the Lpar3((-/-)) females.
Experimental mouse model.
Research laboratories.
Wild-type, Lpar3((+/-)), and Lpar3((-/-)) mice.
Intraperitoneal (IP) administration of prostaglandin E(2) (PGE(2)), cPGI (a stable analogue of PGI(2)), and 11-deoxy prostaglandin F(2α) (11-deoxy PGF(2α), a thromboxane A(2) receptor agonist) to preimplantation gestation day 3.5 Lpar3((-/-)) females.
Implantation sites were detected by blue dye reaction and embryo spacing was determined by the distribution of the implantation sites along the uterine horns on gestation day 4.5; pregnancy outcome was measured by litter size at birth.
Administration of PGE(2) + cPGI on gestation day 3.5 Lpar3((-/-)) females restored on-time implantation but did not affect embryo spacing or the number of implantation sites detected on gestation day 4.5; PGE(2) + cPGI treatment increased litter size at birth. Administration of PGE(2) + cPGI + 11-deoxy PGF(2α) on gestation day 3.5 Lpar3((-/-)) females rescued on-time implantation, partially dispersed the clustered implantation sites normally observed in the Lpar3((-/-)) females, increased the number of implantation sites detected on gestation day 4.5, and increased litter size at birth.
The thromboxane A(2) receptor agonist 11-deoxy PGF(2α) can partially alleviate embryo crowding in the Lpar3((-/-)) females and embryo crowding likely contributes to reduced litter size in the Lpar3((-/-)) females.
Fertility and sterility 03/2012; 97(3):757-63. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effects of bisphenol A (BPA) on embryo and uterine factors in embryo implantation, timed pregnant C57BL6 females were treated subcutaneously with 0, 0.025, 0.5, 10, 40, and 100mg/kg/day BPA from gestation days 0.5-3.5. In 100mg/kg/day BPA-treated females, no implantation sites were detected on day 4.5 but retention of embryos in the oviduct and delayed embryo development were detected on day 3.5. When untreated healthy embryos were transferred to pseudopregnant females treated with 100mg/kg/day BPA, no implantation sites were detected on day 4.5. In 40 mg/kg/day BPA-treated females, delayed implantation and increased perinatal lethality of their offspring were observed. Implantation seemed normal in the rest BPA-treated groups or the female offspring from 40 mg/kg/day BPA-treated group. These data demonstrate the adverse effects of high doses of BPA on processes critical for embryo implantation: embryo transport, preimplantation embryo development, and establishment of uterine receptivity.
Reproductive Toxicology 09/2011; 32(4):434-41. · 3.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the precise timing of progesterone receptor (PR) disappearing from the uterine luminal epithelium (LE) to help understand the significance of the dynamic PR expression in the LE during embryo implantation.
Experimental rodent models.
University research laboratories.
Mice and hamsters.
Pseudopregnancy and artificial decidualization.
Blue dye injection for detecting embryo attachment; immunohistochemistry, immunofluorescence, and in situ hybridization for detecting gene expression.
Progesterone receptor remained expressed in the LE up to 6 hours after the initial detection of blue dye reaction in mice (day 3, 22:00 hours), but disappeared first from LE cells at the implantation site and subsequently from the entire LE layer by day 4, 06:00 hours, when uterine stromal decidualization had become obvious. Progesterone receptor remained highly expressed in the LE of day 4 at 11:00 hours in pseudopregnant mice, but it disappeared from the entire LE layer by day 4 at 06:00 hours in artificially decidualized pseudopregnant mice.
Progesterone receptor disappears from the LE after implantation has initiated and before the histologic decidualization manifests, suggesting an active role of continued PR expression in the LE for the initial implantation process. The disappearance of PR expression in the LE is regulated by uterine factor(s) produced upon embryo attachment.
Fertility and sterility 03/2011; 95(6):2087-93. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine factors differentiating LPA3 from other lysophospholipid (LP) receptors for its role in embryo implantation.
Experimental mouse models.
Institute/university research laboratories.
Wild-type, Lpar3(-/-), Lpar1(-/-)Lpar2(-/-), and S1pr2(-/-)S1pr3(-/-) mice.
Ovariectomy.
Blue dye injection for determining implantation sites on gestation day 4.5. Real-time polymerase chain reaction for measuring gene expression in whole uterus and separated uterine layers. In situ hybridization for detecting progesterone (P)-induced Lpar3 expression in the uterine luminal epithelium (LE).
Normal implantation was observed in Lpar1(-/-)Lpar2(-/-) and S1pr2(-/-)S1pr3(-/-) females. Temporal expression showed peak expression of Lpar3 in the preimplantation uterus and constitutive expression of the other nine LP receptors in the periimplantation uterus. Spatial localization revealed main expression of Lpar3 in the LE and broad expression of the remaining LP receptors in all three main uterine layers: LE, stromal, and myometrial layers. Hormonal regulation in ovariectomized uterus indicated up-regulation of Lpar3 but down-regulation or no effect of the remaining nine LP receptors by P, and down-regulation of most LP receptors, including Lpar3, by 17β-estradiol.
LE localization and up-regulation by P differentiate LPA3 from the other nine LP receptors and may underlie its essential role in embryo implantation.
Fertility and sterility 03/2011; 95(6):2107-13, 2113.e1-4. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lpar3 is upregulated in the preimplantation uterus, and deletion of Lpar3 leads to delayed uterine receptivity in mice. Microarray analysis revealed that there was higher expression of Col3a1 and Col6a3 in the Preimplantation Day 3.5 Lpar3(-/-) uterus compared to Day 3.5 wild-type (WT) uterus. Since extracellular matrix (ECM) remodeling is indispensable during embryo implantation, and dynamic spatiotemporal alteration of specific collagen types is part of this process, this study aimed to characterize the expression of four main uterine collagen types: fibril-forming collagen (COL) I and COL III, basement membrane COL IV, and microfibrillar COL VI in the peri-implantation WT and Lpar3(-/-) uterus. An observed delay of COL III and COL VI clearance in the Lpar3(-/-) uterus may be associated with higher preimplantation expression of Col3a1 and Col6a3. There was also delayed clearance of COL I and delayed deposition of COL IV in the decidual zone in the Lpar3(-/-) uterus. These changes were different from the effects of 17beta-estradiol and progesterone on uterine collagen expression in ovariectomized WT uterus, indicating that the altered collagen expression in Lpar3(-/-) uterus is unlikely to be a result of alterations in ovarian hormones. Decreased expression of several genes encoding matrix-degrading metallo- and serine proteinases was observed in the Lpar3(-/-) uterus. These results demonstrate that pathways downstream of LPA3 are involved in the dynamic remodeling of ECM in the peri-implantation uterus.
Biology of Reproduction 02/2011; 84(2):255-65. · 4.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Proline-rich acidic protein 1 mRNA is highly expressed in the uterine luminal epithelium (LE) of day 0.5 mouse uterus, disappears in the preimplantation day 3.5 uterus, and reappears abundantly in the LE after embryo implantation has occurred or upon artificial decidualization. In ovariectomized uterus, Prap1 is down-regulated by P, transiently down-regulated by E(2) treatment for 6 hours, but dramatically induced by E(2) treatment for 3 days.
Fertility and sterility 12/2010; 94(7):2808-11.e1. · 3.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pregnant mice (n = 3) were exposed to BPA by intraperitoneal injection, from gestation day 9.5 until end of lactation. Male offspring were evaluated for cytokine production at 20 wk-of-age. One pregnant control mouse produced no males, precluding statistical analysis. However, recurring shifts in cytokines were suggested in the adult BPA offspring. Serum showed a numeric increase in 16 of 21 basal cytokine levels. ConA-stimulated splenocytes showed a numeric increase in 17 of 21 cytokines, and LPS-stimulated splenocytes an increase in 18 of 21 cytokines. The cytokine profile was one of T(H)1 up-regulation more than T(H)2, and with skewing toward T(H)17 responses.
International Journal of Environmental Research and Public Health 07/2010; 7(7):2845-52. · 1.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transthyretin (TTR), a carrier for thyroxine and retinol, has its messenger RNA (mRNA) expressed in the glandular endometrial epithelium and its protein detected in the glandular endometrial epithelium and the uterine lumen. TTR mRNA is dramatically up-regulated in the preimplantation mouse uterus as well as the P-treated ovariectomized mouse uterus, and in both situations the up-regulation of TTR is blocked by treatment with the P receptor antagonist RU486.
Fertility and sterility 02/2010; 93(8):2750-3. · 3.97 Impact Factor
