Proteomics of the human endometrium and uterine fluid: a pathway to biomarker discovery

Salamonsen, Lois A.; Edgell, Tracey A.; Rombauts, Luk; Stephens, Andrew N.; Robertson, David; Rainczuk, Adam; Nie, Guiying; Hannan, Natalie J.

doi:10.1016/j.fertnstert.2012.09.013

Cited by 86 publications

(68 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Emerging evidence over the last decade in humans points to roles for uterine glands and their secretory products in uterine receptivity, blastocyst implantation, and postimplantation conceptus (embryo/fetus and associated extraembryonic membranes or placenta) growth and development during the first trimester (56,60,61). Although for many decades the secretions of glands have been hypothesized to play an essential role in sustaining the conceptus before implantation (62,63), their potential role in postimplantation development of the embryo and placenta in humans was largely ignored until recently (60,64). The human conceptus undertakes interstitial implantation beginning around day 7 postfertilization that is completed by day 10-12 (60,65).…”

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

“…Thus, uterine glands continue to function during the first trimester and deliver their contents into the intervillous space where they may play important biological roles in placental development. Indeed, circumstantial evidence suggests that deficient glandular activity may be a causative factor in early pregnancy failure in humans (63,73).…”

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

See 1 more Smart Citation

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

126

177

View full text Add to dashboard Cite

Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.T he uterus is comprised of two tissue compartments, the endometrium and the myometrium. The endometrium contains three cell types, luminal epithelium (LE), glandular epithelium (GE), and stroma. In mice, the uterus becomes receptive to blastocyst implantation on gestational day (GD) 4 (with the observation of a postcoital vaginal plug designated GD 0.5); it is prereceptive on GD 1-3, and by the afternoon of GD 5 it becomes nonreceptive (refractory) (1-3). Dynamic changes in ovarian estrogen and progesterone production act via the uterus to regulate uterine receptivity, blastocyst implantation, and stromal cell decidualization necessary for the establishment of pregnancy (4-6). The implantation process, which is initiated by the attachment of the blastocyst trophectoderm to the receptive LE, occurs before or right after midnight in the evening of GD 4 and becomes more prominent by the morning of GD 5. By GD 6, the trophectoderm begins to contact directly stromal cells that then begin to differentiate into decidual cells, which are required for successful pregnancy because they regulate placental development and local maternal immune responses (7,8).The infertility observed in leukemia inhibitory factor (Lif)-null mice and uterine gland-knockout (UGKO) mice and sheep established ...

show abstract

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

126

177

View full text Add to dashboard Cite

show abstract

“…The histotroph contains proteins, amino acids and lipids essential for early embryo development (Ribeiro et al, 2016), and any induced change in the histotroph as a result of uterine sampling may subsequently adversely affect early placental development (Dorniak et al, 2013). However, aspiration of histotroph has been performed in women on the same day of ET without affecting PR (van der Gaast et al, 2003, Boomsma et al, 2009a, Salamonsen et al, 2013. Differences in attachment process between women and cattle may explain these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

63 Effect of Endometrial Biopsy on Uterine Health of Tropically Adapted Beef Cattle

Ramirez-Garzon

Satake

Lyons

et al. 2017

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

In cattle, early embryonic loss during the first two to three weeks after fertilisation is recognised as the major cause of reproductive failure, with consequent significant impacts on business performance of beef and dairy farms. Inadequate endometrial receptivity is considered an important cause of early embryonic mortality in cattle. A pilot experiment was conducted to compare the outcome of performing different endometrial sampling procedures in tropically adapted (Bos indicus x Bos taurus) heifers, and to select the most suitable method to collect samples for investigation of endometrial gene expression. Endometrial biopsy (EB) using a biopsy device with a diameter similar to an artificial insemination gun (10366L Karl Storz®, Germany) was found to be the most reliable method of collecting endometrial samples in these heifers, with the samples recovered yielding a mean concentration of RNA of 72.9 ±39.3 ng/µl and mean RNA integrity number (RIN) of 7.3 ±1.1.To assess the likely safety of conducting EB in cattle a systematic review of published information assessing the impact of EB on subsequent pregnancy rates was conducted. Using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol, online searches identified 1164 possible studies. After applying the exclusion criteria, six studies allowed the comparison of pregnancy rates between sampled (n= 1,208) and non-sampled cows (n=2,393). The results showed that EB can be performed before breeding without adversely affecting the likelihood of cows becoming pregnant.A major objective of the research was to determine whether EB and evaluation of endometrial gene expression could be used to identify tropically adapted embryo transfer (ET) recipients more likely to become pregnant. Three potential EB scenarios were investigated, 1) EB on Day 7 of the oestrous cycle prior to the cycle when ET would be performed, 2) EB on Day 4 of the oestrous cycle in which ET would be performed i.e. EB 3 days before ET, and 3) EB on the same day when ET would be performed.The first study assessed the morphological and inflammatory changes induced by endometrial biopsy. Pre-synchronised heifers underwent EB from the horn ipsilateral to the corpus luteum (CL) either at Day 7 of the previous cycle (Group 1 n=10) followed by administration of a luteolytic dose of prostaglandin F2α or at Day 4 (Group 2, n=7) of the present cycle. All heifers were slaughtered on Day 7 of the present cycle. The site of EB was visually evident in 40% (4/10) of Group 1 and 42% (3/7) of Group 2 heifers. Histological assessment revealed no evidence of changes indicative of endometritis in either the biopsied or non-biopsied horns in both groups. The histological iii changes observed included mild mononuclear infiltration of the epithelium and mild vascular changes associated with haemorrhage and congestion.Initial investigation of the endometrial expression of the pro-inflammatory cytokine IL1β and wound healing cytokine TGFβ genes found no significant difference betwe...

show abstract

“…Aberrant endometrial receptivity is one of the major causes of female infertility and ART failure and has justifiably gained attention as potential source of biomarkers to help reduce unsuccessful ART cycles (109). Proteomic profiling of human endometrium during the proliferative and secretory phase led to the identification of five proteins with altered expression, of which glutamate NMDA receptor subunit zeta 1 precursor and FRAT1 were differentially expressed in the secretory endometrium in the study of DeSouza et al (110).…”

Section: Proteomics and Endometrial Receptivitymentioning

confidence: 99%