Endometrial Development and Adenogenesis in the Neonatal Pig: Effects of Estradiol Valerate and the Antiestrogen ICI 182,7801

Tarleton, Becky J.; Wiley, Anne A.; Bartol, Frank F.

doi:10.1095/biolreprod61.1.253

Cited by 68 publications

(65 citation statements)

References 36 publications

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“…Neonatal porcine uterine development is both ESR1 dependent and estrogen sensitive (Bartol et al 1993, Tarleton et al 1999, 2003, Chen et al 2010. Therefore, it was important to determine the extent to which uterine ESR1 expression might be regulated via a lactocrine mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Between birth and PND 3, the porcine endometrium undergoes an important morphogenetic transition, as glandular epithelium differentiates from luminal epithelium and nascent uterine glands begin to penetrate underlying stroma (Masters et al 2007). These events are both ER dependent and estrogen sensitive (Bartol et al 1993, Tarleton et al 1999, 2003, Chen et al 2010. Data support the idea that factors affecting patterns of porcine uterine ESR1 expression and ER activation during early postnatal life define both the developmental program and trajectory of developing uterine tissues with lasting consequences in adults.…”

Section: Introductionmentioning

confidence: 91%

“…Development of the neonatal porcine uterine wall is marked by age-dependent expression of estrogen receptor-a (ESR1), which is low to undetectable at birth (postnatal dayZPND 0; Yan et al 2006a), evident in nascent endometrial glandular epithelium and underlying stroma by PND 2 (Yan et al 2008), and develops in an endometrial cell compartment-specific manner during the first 2 weeks of postnatal life (Tarleton et al 1999). Between birth and PND 3, the porcine endometrium undergoes an important morphogenetic transition, as glandular epithelium differentiates from luminal epithelium and nascent uterine glands begin to penetrate underlying stroma (Masters et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Milk-borne lactocrine-acting factors affect gene expression patterns in the developing neonatal porcine uterus

Chen¹,

Frankshun²,

Wiley³

et al. 2011

Reproduction

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Lactocrine communication of milk-borne bioactive factors (MbFs) from mother to offspring through nursing can affect neonatal development with lasting consequences. Relaxin (RLX), a lactocrine-active peptide found in porcine colostrum, stimulates estrogen receptor-a (ESR1) expression required for uterine development shortly after birth (postnatal dayZPND 0). Whether other MbFs or cooperative lactocrine mechanisms affect the neonatal uterine developmental program is unknown. To determine the effects of age, nursing, and exogenous RLX on gene expression associated with uterine development, gilts (nZ4-5/group) were assigned to nurse ad libitum or to receive milk replacer, with or without exogenous RLX (20 mg/kg BW i.m./6 h for 48 h), from birth to PND 2 when uteri were collected. Body weight and uterine weight increased (P!0.05) similarly from birth to PND 2 in all gilts. However, colostrum consumption was required for normal uterine ESR1, vascular endothelial growth factor (VEGFA), matrix metalloproteinase 9 (MMP9), and RLX receptor (RXFP1) protein and/or transcript expression on PND 2. Uterine ESR1, VEGFA, and MMP9 protein levels were below (P!0.01) the assay sensitivity in replacer-fed gilts. Supplemental RLX increased (P!0.05) uterine ESR1 protein and mRNA in nursed gilts, as well as VEGFA protein in nursed and VEGFA mRNA in both nursed and replacer-fed gilts. RLX treatment did not affect uterine MMP9 mRNA levels. When compared with replacer-fed gilts on PND 2, uterine RXFP1 mRNA was reduced (P!0.05) in nursed gilts and in RLX-supplemented replacer-fed gilts. These results constitute the first evidence that establishment of the neonatal porcine uterine developmental program requires maternal lactocrine support.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Milk-borne lactocrine-acting factors affect gene expression patterns in the developing neonatal porcine uterus

Chen¹,

Frankshun²,

Wiley³

et al. 2011

Reproduction

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“…In contrast to the partial estrogen receptor antagonist tamoxifen, ICI 182,780 is an exclusive antiestrogen due to its lack of estrogen-like activity (45)(46)(47)(48). Furthermore, ICI 182,780 causes disassociation of receptor-associated proteins, an impaired receptor dimerization and increased receptor degradation (49,50).…”

Section: Tlr7-induced Ifn-␣ Levels Are Not Influenced By Exogenous 17mentioning

confidence: 99%

TLR7 Ligands Induce Higher IFN-α Production in Females

Berghöfer

Frommer

Haley

et al. 2006

The Journal of Immunology

412

329

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IFN-α exercises multiple immune modulatory and antiviral activities and has been suggested to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) release IFN-α upon TLR7 and TLR9 ligation. With respect to the nine times higher incidence of SLE in women and the clinical use of synthetic TLR ligands as novel immune adjuvants, we analyzed IFN-α and TNF-α production in healthy human individuals. Blood samples were incubated with synthetic TLR7 and TLR9 ligands. In three independent groups (n1 = 120, n2 = 101, and n3 = 123), analysis revealed a capacity of female PBLs to produce significantly higher IFN-α levels after TLR7 stimulation (p1 < 0.0000001, p2 < 0.0000001, and p3 < 0.0001) compared with male PBLs. In contrast, no sex differences were evident after TLR9 stimulation. TNF-α production after TLR7 stimulation and also total pDC numbers were not different between females and males. X-inactivation escape of the TLR7 gene was investigated in monoclonal B cell lines and, independently, in pDCs after cell sorting and single-cell picking, indicating regular silencing of one TLR7 allele in females. Additionally, exogenous 17β-estrogen and estrogen receptor antagonism did not indicate a significant role on TLR7-induced IFN-α production. Our data reveal for the first time a profound sex-dependent pathway of TLR7-induced IFN-α with higher production in females. These findings may explain the higher prevalence of SLE in females and the reported decreased therapeutic efficacy of synthetic TLR7 ligands in male individuals.

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“…In the pig (Sus scrofa domesticus), uterine glands are absent at birth (postnatal day (PND) 0) and the uterus is estrogen receptor-a (ESR1) negative (Tarleton et al 1998, Yan et al 2006a. However, during the first 2 weeks of life, uterine glands differentiate and ESR1 expression is evident in both nascent glandular epithelium and endometrial stroma (Tarleton et al 1999). These events are ovary independent and estrogen-sensitive (Bartol et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Chen¹,

Wiley²,

Ho³

et al. 2010

Reproduction

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Disruption of estrogen-sensitive, estrogen receptor (ER)-dependent events during porcine uterine development between birth (postnatal dayZPND 0) and PND 14 affects patterns of uterine morphoregulatory gene expression in the neonate with lasting consequences for reproductive success. Uterine capacity for conceptus support is reduced in pregnant adult gilts exposed to estradiol valerate (EV) for 14 days from birth. Objectives here were to determine effects of EV exposure from birth through PND 13 on neonatal uterine and adult endometrial markers of growth, patterning, and remodeling. Targets included the relaxin receptor (RXFP1), estrogen receptor-a (ESR1) and vascular endothelial growth factor (VEGFA), morphoregulatory markers HOXA10 and WNT7A, and the matrix metalloproteinases (MMP)2 and MMP9. Gilts were treated daily with EV (50 mg/kg body weight per day, i.m.) or corn oil vehicle from birth through PND 13. Uteri were obtained from neonates on PND 14 and from adults on pregnancy day 12 (PxD 12). In neonates, EV exposure from birth increased uterine RXFP1 gene expression, and both ESR1 and VEGFA proteins. At PxD 12, endometrial RXFP1 mRNA remained elevated, while ESR1 protein was reduced. Early EV treatment decreased neonatal uterine WNT7A, but increased HOXA10 expression. WNT7A expression was reduced in EV-treated adults. Transient EV exposure increased MMP9 transcripts at PND 14, whereas both latent and active MMP9 activity was increased due to early EV treatment in adults on PxD 12. Results support the hypothesis that transient, estrogen-induced disruption of porcine uterine development from birth alters early programming events that lead to functional consequences in the adult.

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Endometrial Development and Adenogenesis in the Neonatal Pig: Effects of Estradiol Valerate and the Antiestrogen ICI 182,7801

Cited by 68 publications

References 36 publications

Milk-borne lactocrine-acting factors affect gene expression patterns in the developing neonatal porcine uterus

Milk-borne lactocrine-acting factors affect gene expression patterns in the developing neonatal porcine uterus

TLR7 Ligands Induce Higher IFN-α Production in Females

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

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