Neonatal estradiol exposure alters uterine morphology and endometrial transcriptional activity in prepubertal gilts

While uterotrophic effects of relaxin are well documented, the mechanism through which relaxin promotes uterine growth is incompletely understood. Studies in rats suggest that relaxin-stimulated uterine edema depends on estrogen receptor (ER) activation. Here, neonatal pigs were used to investigate the interaction between relaxin and ER signaling pathways. Gilts were treated either at birth (postnatal day (PND) 0) (study 1) before the onset of endometrial ERa expression, or on PND 12 (study 2) after the onset of ERa expression. In study 1, gilts were treated with estradiol-17b or porcine relaxin for two days and uteri were collected on PND 2. In study 2, PND 12 gilts were treated with a single injection of the ER antagonist ICI 182,780 (ICI) or vehicle. Two hours later, gilts were given either estradiol-17b or porcine relaxin for two days. When administered for two days from birth (study 1), neither estradiol-17b nor relaxin affected uterine weight or protein content. However, uterine luminal epithelial height was greater in relaxin-than in vehicle-treated gilts. In contrast, in study 2, both estradiol and relaxin increased uterine weight, protein content and uterine luminal epithelial height on PND 14. These effects were inhibited by pre-treatment with ICI in both estradiol-and relaxin-treated gilts. The results indicate that uterotrophic effects of relaxin in the neonatal pig are related to age and to both the relative presence and state of activation of the ER system in developing uterine tissues between birth and PND 14.

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

“…Moreover, aberrant activation of the ER system can have lasting consequences for FRT morphology and function (Miller et al 1998, Markey et al 2005. In the pig, this is supported by evidence that the neonatal uterus: i) is ERanegative at birth (Tarleton et al 1998); ii) develops sensitivity to estrogen between birth (postnatal dayZPND 0) and PND 15 that is associated with the appearance and proliferation of endometrial glands and the expression of ERa in the stroma and glandular epithelium (Tarleton et al 1998(Tarleton et al , 2001; and iii) responds to transient estrogen exposure from birth with affects on adult phenotype, uterine responses to conceptus signals, and uterine capacity to support pregnancy (Tarleton et al 2001(Tarleton et al , 2003.…”

Section: Introductionmentioning

confidence: 98%

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

Yan¹,

Chen²,

Wiley³

et al. 2008

The porcine female reproductive tract undergoes estrogen receptor (ER) a-dependent development after birth (postnatal dayZPND 0), the course of which can determine adult uterine function. Uterotrophic effects of relaxin (RLX) in the porcine neonate are age specific and may involve ER activation. Here, objectives were to determine effects of RLX and estrogen administered from birth on uterine and cervical growth and expression of ERa, vascular endothelial growth factor (VEGF), and the RLX receptor (RXFP1). On PND 0, gilts were treated with the antiestrogen ICI 182 780 (ICI) or vehicle alone and, 2 h later, were given estradiol-17b (E) or porcine RLX for 2 days. Neither RLX nor E affected uterine wet weight or protein content on PND 2. However, RLX, but not E, increased cervical wet weight and protein content when compared with controls. Pretreatment with ICI did not inhibit RLX-stimulated cervical growth. Uterine and cervical ERa increased in response to RLX, but not E. Both RLX and E increased VEGF in the uterus and cervix on PND 2. Pretreatment with ICI increased VEGF in both tissues and increased RLX-induced cervical VEGF. In the uterus E, but not RLX, increased RXFP1 mRNA. In the cervix, E increased RXFP1 gene expression whereas RLX decreased it. Results indicate that the neonatal uterus and cervix are sensitive to E and RLX and that growth responses to RLX in these tissues differ by PND 2. Effects of RLX on uterine and cervical ERa and VEGF expression may be important for neonatal reproductive tract development. Reproduction (2008) 135 705-712

“…Histologically, the adult porcine cervix is lined by columnar luminal epithelium (LE) and contains epithelial crypts that penetrate the adluminal stroma (St; Eldridge-White et al 1989, Winn et al 1993. Features of neonatal porcine uterine development are defined more completely with respect to both patterns of endometrial histogenesis (Bartol et al 1993) and periods of postnatal life, during which disruption of the uterine developmental program can affect the organizational trajectory and, ultimately, phenotype of the endometrium (Tarleton et al 2001). For the porcine uterus, imposition of the lactocrine-null state for 48 h from birth (postnatal day 0 (PND0)), by feeding milk replacer in lieu of nursing, alters patterns of endometrial development .…”

Section: Introductionmentioning

confidence: 99%

Effects of age, nursing, and oral IGF1 supplementation on neonatal porcine cervical development

Camp¹,

Wiley²,

Boulos³

et al. 2014

Nursing supports neonatal porcine uterine and testicular development, however, lactocrine effects on cervical development are undefined. Studies were conducted to determine the effects of i) age and the imposition of the lactocrine-null state from birth (postnatal day 0 (PND0)) by milk replacer feeding on cervical histology; ii) imposition of the lactocrine-null state for 2 days from birth on cervical cell proliferation, as reflected by proliferating cell nuclear antigen immunostaining; and iii) a single feeding of colostrum or milk replacer, administered at birth, with or without oral IGF1, on cervical cell proliferation and phosphorylated AKT (pAKT) and B-cell lymphoma 2 (BCL2) protein levels at 12 h postnatal. Cervical crypt depth and height of luminal epithelium (LE) increased with age by PND14, when both responses were reduced in replacer-fed gilts. Cell proliferation was reduced in LE at PND2, and in crypt epithelium and stroma by PND14 in replacer-fed gilts. Returning replacer-fed gilts to nursing on PND2 did not rescue the cervical phenotype by PND14. A single feeding of colostrum, but not milk replacer, was sufficient to support cervical cell proliferation at 12 h postnatal. IGF1 supplementation induced cell proliferation in replacer-fed gilts, and increased cervical pAKT and BCL2 levels in colostrum-fed gilts and replacer-fed gilts at 12 h postnatal. Results indicate that age and nursing support porcine cervical development, support is initiated at first ingestion of colostrum, IGF1 may be lactocrine-active, and identification of lactocrine-active factors can be accomplished by 12 h postnatal using this bioassay system.