Quantitative morphological changes in the interplacentomal wall of the gravid uterine horn of cattle during pregnancy
© Albers et al.; licensee BioMed Central. 2015
Received: 27 October 2014
Accepted: 14 April 2015
Published: 18 April 2015
The interplacentomal wall of the gravid uterine horn in cattle is the subject of reports dealing mainly with specific aspects of early pregnancy or the peripartal period. Only a very limited number of early and descriptive studies includes the whole period of pregnancy. Thus, there is a gap concerning quantitative morphological data of the uterine wall during pregnancy. We hypothesized that the specific requirements of pregnancy are reflected by significant and characteristic morphologic changes.
Interplacentomal segments of the fetus-bearing horn of the uterus of 47 cows were collected at slaughter, assessed quantitatively by light microscopy, grouped into trimesters (trim), and data were analyzed statistically.
During pregnancy there were significant increases (p<0.05) in the measured parameters: heights of the endometrial surface epithelium (31 increased to 46 and 46 μm, in the 1st, 2nd and 3rd trim, respectively), glandular epithelium (19.6 to 22.4 and 25.4 μm, respectively), diameters of glands (94 to 166 to 239 μm, respectively) and glandular lumina (56 to 122 to 188 μm, respectively). Volume density of the glandular epithelium did not change, while that of glandular lumina increased significantly (8 to 26 to 40% in the 1st, 2nd and 3rd trim, respectively) and of endometrial stroma decreased with ongoing pregnancy (67 to 46 to 37%; p<0.05).
Diameters of myometrial smooth muscle cells (MSMC) (9.7 to 12.4 and 12.9 μm, respectively, for the 1st, 2nd and 3rd trim; p<0.05), and the volume fraction of myometrial stroma increased (6 to 10 to 13%; p<0.05), while decreases were observed in MSMC nuclear volume density (4.4 and 4.0 to 2.4%; p<0.05). The fraction of MSMC cytoplasm (89 to 85%) and the nucleus:cytoplasm ratio (0.05 to 0.03%) both decreased for the 1st vs. 3rd trim, respectively (p<0.05).
These results indicate that the interplacentomal wall of the gravid uterine horn is subjected to significant morphological changes during pregnancy, underlining the importance of endometrial surface epithelium and of gland hypertrophy for nourishment of the conceptus, of increased myometrial extracellular matrix for uterine tensile strength and of myometrial smooth muscle hypertrophy for expulsion of the fetus at term.
The interplacentomal wall of the gravid uterine horn in cattle has, besides many other important functions, three major tasks during pregnancy: secretion of uterine milk, provision of uterine tensile strength and mechanical stability, and expulsion of the fetus at term.
To meet these requirements, the uterus is supplied with endometrial glands (EG), which are essential, at least during early pregnancy, for nourishment of the growing fetus [1-3]. Fetal growth during pregnancy requires concomitant uterine enlargement and increasing tensile strength, which are paralleled by an increase in uterine mass [4-6]. In placentomes, the latter is accomplished predominantly by hyperplasia [6-10]. Within the interplacentomal uterine wall, however, hypertrophy is the main contributor to tissue gain, as revealed by qualitative, i.e., non-quantitative morphological, biochemical and histochemical studies [6,7,10-15]. Synthesis of interstitial matrix proteins at specific sites [16,17] and accumulation of contractile proteins [18-21] augment uterine wall tensile strength and contractile force. We therefore hypothesized that the specific requirements of pregnancy are reflected by significant and characteristic morphological changes and that the cause of the increased interplacentomal uterine mass, i.e., hypertrophy, is reflected by low mitotic indices.
Although some early measurements on uterine glands are available, made almost 50 years ago, they lack adequate statistical analysis  and no recent quantitative and thoroughly statistically evaluated data encompassing all structural elements of the uterine wall are available on the morphological changes occurring within the interplacentomal wall of the gravid uterine horn of cattle. In the present study, appropriate specimens were analysed morphometrically and also, for the first time, stereologically. The results are discussed in the light of histochemical findings obtained from the same samples [15,16,21] and from other reports published elsewhere using qualitative morphological and functional parameters [for references see below].
The uteri of pregnant Holstein–Friesian cows were collected at an abattoir (Vosding, Gleidingen, Germany) and 5 to 6 organs for each of the months 1–9 of gestation were selected at random for the present study. Within 30 min after the animals were killed, they were eviscerated, the pregnant uteri opened and the crown-rump length of the 47 embryos or fetuses present was recorded to estimate fetal age, as follows: up to 1.5 cm, 1 month (n=4); 2–4 cm, 2 months (n=5); 6–8 cm, 3 months (n=5); 15–23 cm, 4 months (n=6); 26–32 cm, 5 months (n=6); 36–44 cm, 6 months (n=5); 48–55 cm, 7 months (n=6); 60–67 cm, 8 months (n=5); and 70–82 cm, 9 months (n=5) . In one case out of the four first month specimens, the tiny embryo was not found macroscopically, thus, the uterine contents of the early pregnant animal were examined histologically so that the embryonic tissues could be detected.
Tissue sampling and processing
A piece of the interplacentomal wall of the gravid uterine horn measuring 3 cm × 3 cm and the adherent allantochorion were excised from each animal. The tissues were cut into three strips of equal width and immersed in 4% neutral buffered formaldehyde solution (v/v) according to Lillie  for 24 h, rinsed in tap water, dehydrated in a graded series of ethanol and acetic acid-n-butyl ester (Riedel-de-Haën, Seelze, Germany) and embedded in Paraplast Plus(R) (Sherwood Medical, St. Louis, MO, USA).
Histological techniques and staining procedures
Tissues were cut at 5 μm (1140/Auto-cut(R), Reichert-Jung, Heidelberg, Germany), then sections were mounted onto glass slides and routinely stained with hematoxylin-eosin and Masson-Goldners trichrome stain .
All measurements were performed at a magnification of x400 using a computerized and calibrated measuring device (CUE 3(R), version 4.5, Galai Productions Ltd., Migdal Haemek, Israel). Slides, one per animal, were assessed on a video screen.
The following parameters were evaluated using point-to-point distance measurement with the computer mouse: (I) height of the endometrial surface epithelium (SE), (II) height of the epithelium of intermediate and deep endometrial glands (IGE, DGE, respectively), (III) diameter of intermediate and deep glands (IG, DG), respectively, (IV) diameter of the lumen of IG and DG, and (V) diameter of myometrial smooth muscle cells (MSMC). Epithelial heights were measured at 50 randomly selected locations for each slide. Gland and gland lumen diameters were assessed at 30 locations in randomly selected round profiles. MSMC diameter was measured in 50 round profiles per section, i.e., per animal.
To analyze the differential structural and cellular compositions of the interplacentomal uterine wall stereologically, volume densities (Vv) were estimated. For this, a transparent test lattice of point probes, each represented by the crossing of equidistant vertical and horizontal lines and representing 500 cross-points, was used. Cross-points situated exactly on the border between two adjacent structures accounted for the structure extending to the left and downwards from the cross-point. Three randomly selected endometrial and myometrial tissue fields, each representing 500 cross-points, were assessed for the following elements: (I) endometrial stroma, glandular epithelium, glandular lumen, and (II) myometrial stroma, MSMC cytoplasm and MSMC nuclei. These data were used to calculate Vv of these elements within the endometrium and myometrium, respectively. Finally, the nucleus:cytoplasm ratio (NCR) was assessed for SE and IGE/DGE by counting nuclear and cytoplasmic hits within the epithelia, each performed in 10 randomly selected microscopic fields and encompassing at least 500 cross-points as well as the NCR of MSMC.
Mean values of morphometric and stereologic data of a section, i.e., representing a single animal, were used for further analysis. Animals were grouped into trimesters (trim 1–3, i.e., months 1–3 (n=14), months 4–6 (n=17) and months 7–9 (n=16), respectively). Data were analyzed statistically using SAS(R) software (SAS Institute Inc., Gary, NC, USA). After checking for normal distribution, analysis of variance (ANOVA) and the Tukey test for post hoc analysis were used to evaluate the influence of time (i.e., trim). The Tukey test uses the experiment-wise error rate. Differences with a P-value < 0.05 were designated as significant.
Morphometry and stereology
Morphometric and stereologic data of the interplacentomal uterine wall in cattle during pregnancy (mean value ± SD)
1st trimester (n=14)
2nd trimester (n=17)
3rd trimester (n=16)
height of SE (μm)
31.26 +/− 11.87a
46.31 +/− 8.40b
45.61 +/− 5.63b
NCR of SE
0.42 +/− 0.08a
0.51 +/− 0.15a
0.51 +/− 0.09a
height of IGE/DGE (μm)
19.59 +/− 3.41a
22.42 +/− 2.02b
25.43 +/− 3.09c
NCR of IGE/DGE
0.58 +/− 0.11a
0.44 +/− 0.07b
0.54 +/− 0.12a
diameter of IG/DG (μm)
94.2 +/− 19.3a
166.0 +/− 36.6b
239.1 +/− 46.1c
lumen diameter of IG/DG (μm)
55.9 +/− 16.1a
122.4 +/− 35.8b
187.9 +/− 41.1c
Vv of EGE/EM (%)
24.6 +/− 5.5a
24.2 +/− 4.7a
22.9 +/− 5.5a
Vv of EGL/EM (%)
8.2 +/− 5.7a
26.1 +/− 10.8b
40.1 +/− 10.9c
Vv of ES/EM (%)
67.2 +/− 8.5a
46.1 +/− 6.7b
37.0 +/− 10.0c
diameter of MSMC (μm)
9.71 +/− 1.16a
12.43 +/− 1.37b
12.93 +/− 1.37b
NCR of MSMC
0.050 +/− 0.024a
0.047 +/− 0.017a
0.028 +/− 0.010b
Vv of MSMC nuclei/MM (%)
4.41 +/− 2.02a
4.00 +/− 1.41a
2.36 +/− 0.85b
Vv of MSMC cytoplasm/MM (%)
89.34 +/− 3.90a
86.34 +/− 3.29ab
85.00 +/− 5.01b
Vv of MS/MM (%)
6.11 +/− 3.03a
9.66 +/− 2.99ab
12.65 +/− 5.25b
The diameter of MSMC (Table 1) was significantly lower in the 1st trim compared to the 2nd and 3rd trim. MSMC NCR decreased significantly between the 2nd and 3rd trim. Vv of MSMC cytoplasm and nuclei decreased significantly during pregnancy, while Vv of myometrial stroma increased significantly towards term.
This morphometric study, for the first time also using stereological methods and an appropriate statistical analysis of the data obtained, clearly indicates that the various elements of the bovine interplacentomal wall of the gravid uterine horn, as we hypothesized, are subjected to profound histomorphological changes during pregnancy. These alterations, which were already visible at the light microscopic level (Figure 1), were quantified by measurements using a calibrated computerized microscope measuring device and were found to be significant for many of the parameters evaluated (see Table 1). For interpretation of absolute values, it has to be considered that potential shrinkage artefacts due to histological preparation cannot be excluded. However, since all groups were subjected to exactly the same methodology, it is likely that relative data as well as group comparisons and thus developmental changes during pregnancy were unaffected.
The important role of the uterine SE is underlined by its continuous presence as a lining throughout pregnancy. This is in contrast to an early report stating that the SE is completely lacking during early pregnancy in cattle . As evidenced by its expression of genes for many proteins, such as uterine milk proteins (UTMP) , glucose transporter-1 [26,27], calbindin D9k [28,29], transient receptor potential channel type 6 , MMP-2 and 9 , SOLD1 , TIMP-2 , EMMPRIN, an inducer of MMPs , galectins 3, 4, and 9 , and COX-2 [33,34], SE is involved in numerous functions during different phases of pregnancy, such as histiotrophic nourishment of the fetus, materno-fetal glucose and calcium transfer, endometrial restructuring, immunomodulation in favor of the fetus, and oxytocin-induced prostaglandin F2alpha production at term. The expression of receptors for estrogens [15,35] growth hormone , various elements of the IGF system , prostaglandins E and F2alpha [33,34], oxytocin  and glucocorticoids [15,35], sheds a light on various hormones and other factors of maternal and fetal origin influencing SE function during pregnancy. The lack of progesterone receptors in the SE during pregnancy is overcome by progesterone-sensitive subepithelial stromal cells producing paracrine-acting factors, such as growth factors , which in turn regulate SE function via their receptors expressed on SE and thus may also initiate SE hypertrophy and hyperplasia. Thus, the continuous presence of the SE is required during the whole of gestation. The highly active protein synthesis machinery and the secretion of uterine proteins [25,39] are reflected in the increasing SE height during early pregnancy, reaching a plateau by the 2nd trimester and maintaining this height until term. This pattern is in contrast to an early histomorphological description indicating no differences in SE height during pregnancy  and also to the maternal crypt epithelium of the bovine placentome, which becomes flattened and discontinuous towards term, a process named “placental maturation” . Desquamated apoptotic SE cells may also be engulfed by the chorion, and thus contribute to histiotrophe in a holocrine manner [15,41].
EG play important roles during the entire course of pregnancy. This is reflected by significant increases in the height of the EG cells and in the lumen and gland diameters found in IG and DG in this study, objectifying earlier non-quantitative histomorphological descriptions and measurements that were inadequately statistically analysed [11,13]. Interestingly, as detected for the first time in this study, the Vv of EG cells did not change during pregnancy and this supports the concept of their consistent physiological relevance during all stages of pregnancy. The increase in IGE/DGE diameter and height therefore should be achieved by a reduction in their length. Endometrial secretions, called uterine milk (UTM) or histiotrophe, play an important role especially during early pregnancy, as demonstrated in the uterine gland knock-out ewe (UGKO), in which normal hatched blastocysts fail to undergo further development during the peri-implantation period since osteopontin and GlyCAM-1 are absent in uterine secretions of UGKO ewes. These proteins are essential for implantation in the ewe because they serve as ligands for integrins or as factors that affect their affinity state at the maternal-conceptus interface (see e.g., ). UTM proteins are important for blastocyst elongation [27,39] and contain immunosuppressive components protecting the embryo from attacks by the maternal immune system . They are secreted mainly by EG cells [25,43,44] during the entire pregnancy . The amount of secretions, however, decreases with ongoing gestation and is paralleled by in vitro endometrial oxygen consumption, which is higher than that observed in caruncular, cotyledonary and intercotyledonary chorioallantois tissues .
EG epithelial cells exhibit a decreasing immunohistochemical staining for progesterone receptors with ongoing pregnancy, together with low levels of estrogen receptor immunoreactivity, while glucocorticoid receptor staining increases with ongoing pregnancy in glandular openings . Furthermore, EG are also supplied with growth hormone receptors , IGF-I receptor [37,45] and prostaglandin E and F2alpha receptors [33,34] and thus are regulated directly by progesterone plus the same hormones and factors as the SE. Proteins expressed by the SE such as uterine milk proteins (UTMP) , glucose transporter-1 [26,27], calbindin D9k [28,29], transient receptor potential channel type 6 , MMP-2 and 9 , TIMP-2 , galectins 3, 4, and 9 , COX-2 [33,34], which have all been detected immunohistochemically in EG epithelia, indicate that EG are, similar to the SE, also involved in histiotrophic nourishment of the fetus, materno-fetal calcium transfer, endometrial restructuration, immunomodulation, and oxytocin-induced prostaglandin F2alpha production at term.
As for the SE, hyperplasia seems to play a minor role in glandular increases in diameter since small numbers of mitoses could be detected in only a few specimens and apoptosis is a sporadic event. This is supported by earlier, non-quantitative histomorphological [11,13] and semi-quantitative Ki-67 immunohistochemical studies  and is also reflected by generally low numbers of mitotic cells in the endometrium detected by flow cytometry .
The formation of a subepithelial mesh of connective tissue and the tremendous increase in diameter of the IGE and DGE necessitates a massive remodelling of the endometrial connective tissue, which is reflected by the expression of MMP-2 and −9 . MMP-2 was localized immunohistochemically within the subepithelial mesh and in periglandular regions, while MMP-9 and TIMP-2 were detected in the SE and EG cells . The mesh increases in thickness during pregnancy months 1 to 5 and possibly constricts glandular openings, which therefore cannot increase in diameter, as do IG and DG. It was analysed immunohistochemically and found to be composed mainly of collagen type I and III fibres and therefore should increase the tensile strength of the uterine wall . Stromal cells within this layer also contained smooth muscle actin and were surrounded by collagen type IV, implying transformation of these cells to myofibroblasts . During pregnancy, endometrial stromal cells express receptors for progesterone and are thus the main cell type mediating progesterone action within the endometrium. Secretions of EG, which are supplied with minimal amounts of progesterone receptors, or even completely lacking them, are activated and sustained via a servomechanism including progesterone-sensitive periglandular stromal cells producing paracrine factors, such as growth factors [2,37,45]. Estrogens, glucocorticoids [15,35], PGs E and F2α [33,34] and growth hormone  directly regulate endometrial stromal function via their receptors. In this study, endometrial stroma Vv decreased significantly with ongoing pregnancy (67.2 vs. 37.0%), reflecting the five-fold increase in EG lumen Vv (8.2 vs. 40.1%). Thus, the endometrial stroma distribution pattern profoundly changes during the first half of pregnancy.
The main changes in myometrial histomorphology, i.e., significant increase in MSMC diameter and significant decrease in nucleus:cytoplasm ratio of MSMC, besides the absence of mitoses in MSMC, strongly suggest hypertrophy and not hyperplasia of these cells during pregnancy. This is in agreement with early microscopic descriptions, which were not verified by measurements [11,12], and a study using Ki-67 immunohistochemistry . These results are, however, in contrast to the rat myometrium, which exhibits a proliferative phase lasting from gestational days 6 to 14 . In sheep and rat, the increase in MSMC cytoplasm is reflected by increases in actin and in smooth muscle myosin heavy chain SM2 protein and other contraction-associated proteins [18-20,48]. Structural elements of the MSMC cytoskeleton parallel these events , which are completed by an increase in gap junction-forming connexin 43 protein immediately preterm . This final step transforms the myometrium into an electrical syncytium capable of synchronized contractions, i.e., exhibiting a parturient pattern of myometrial activity, and expulsion of the fetus [50,51]. Besides the increase in size of MSMC because of the cytoplasmic accumulation of cytoskeletal and contraction-associated proteins, the synthesis of these proteins and of ECM materials, of receptors for ovarian steroids and other hormones and the secretion of prostaglandins may to varying degrees also contribute to the enlargement of these cells [15,33,37,47,48,52-55].
There was a continuous increase in myometrial stroma Vv in the cows of this study. Collagen types I and III slightly increase with ongoing pregnancy . It was shown in the rat that, besides elastin, collagen types I and III are continuously synthesized until the preterm fall in progesterone, when basement membrane proteins such as collagen type IV and laminin ß2 are synthesized together with fibronectin and integrins [17,47,49], thus coupling the contractile apparatus via cytoskeleton and basement membrane to the fibrillar collagens of the myometrial stroma, resulting in a system of great tensile strength and contractile force.
The results of this study indicate that the structural elements of the interplacentomal uterine wall, assessed quantitatively and appropriately analysed statistically for the first time, exhibit changes during pregnancy characteristic of hypertrophy, reflecting the needs of the growing fetus and its expulsion at term. They also emphasize the role of the interplacentomal uterine wall, in particular its SE and EG.
The kind support of Dres. V. Janssen, J. Kohtes, and A. Stelljes, Institute of Anatomy, University of Veterinary Medicine Hannover Foundation, for collecting and processing the tissues is acknowledged. Authors are grateful to Dr. Barry Bavister for careful editing of the manuscript.
- Gray CA, Abbey CA, Beremand PD, Choi Y, Farmer JL, Adelson DL, et al. Identification of endometrial genes regulated by early pregnancy, progesterone, and interferon tau in the ovine uterus. Biol Reprod. 2006;74(2):383–94. doi:10.1095/biolreprod.105.046656.View ArticlePubMedGoogle Scholar
- Spencer TE, Bazer FW. Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front Biosci. 2002;7:d1879–98.View ArticlePubMedGoogle Scholar
- Spencer TE, Gray CA. Sheep uterine gland knockout (UGKO) model. Methods Mol Med. 2006;121:85–94.PubMedGoogle Scholar
- Ferrell CL. Maternal and fetal influences on uterine and conceptus development in the cow: I. Growth of tissues of the gravid uterus. J Anim Sci. 1991;69(5):1945–53.PubMedGoogle Scholar
- Prior RL, Laster DB. Development of the bovine fetus. J Anim Sci. 1979;48(6):1546–53.PubMedGoogle Scholar
- Reynolds LP, Millaway DS, Kirsch JD, Infeld JE, Redmer DA. Growth and in-vitro metabolism of placental tissues of cows from day 100 to day 250 of gestation. J Reprod Fertil. 1990;89(1):213–22.View ArticlePubMedGoogle Scholar
- Zheng J, Johnson ML, Redmer DA, Reynolds LP. Estrogen and progesterone receptors, cell proliferation, and c-fos expression in the ovine uterus during early pregnancy. Endocrinology. 1996;137(1):340–8. doi:10.1210/endo.137.1.8536633.PubMedGoogle Scholar
- Schuler G, Wirth C, Klisch K, Failing K, Hoffmann B. Characterization of proliferative activity in bovine placentomes between day 150 and parturition by quantitative immunohistochemical detection of Ki67-antigen. Reprod Domest Anim. 2000;35(3–4):157–62. doi:10.1046/j.1439-0531.2000.00231.x.View ArticleGoogle Scholar
- Boos A, Janssen V, Mulling C. Proliferation and apoptosis in bovine placentomes during pregnancy and around induced and spontaneous parturition as well as in cows retaining the fetal membranes. Reproduction. 2003;126(4):469–80.View ArticlePubMedGoogle Scholar
- Facciotti PR, Rici RE, Maria DA, Bertolini M, Ambrosio CE, Miglino MA. Patterns of cell proliferation and apoptosis by topographic region in normal Bos taurus vs. Bos indicus crossbreeds bovine placentae during pregnancy Reprod Biol Endocrinol. 2009;7:25. doi:10.1186/1477-7827-7-25.View ArticleGoogle Scholar
- Müller E. Schwangerschaftsveränderungen am Uterus des Rindes. Leipzig: University of Leipzig; 1933.Google Scholar
- Hatch RD. Anatomic changes in the bovine uterus during pregnancy. Am J Vet Res. 1941;2:411–6.Google Scholar
- Yamauchi S, Kakishita T, Kotera K. Histological study of the pregnant uterus in the cow. II. General histological study on the uterine glands. Bull Osaka Prefect Univ. Ser B Agric Life Sci. 1969;21:147–66.Google Scholar
- King GJ, Atkinson BA. The bovine intercaruncular placenta throughout gestation. Anim Reprod Sci. 1987;12(4):241–54.View ArticleGoogle Scholar
- Boos A, Kohtes J, Janssen V, Mulling C, Stelljes A, Zerbe H, et al. Pregnancy effects on distribution of progesterone receptors, oestrogen receptor alpha, glucocorticoid receptors, Ki-67 antigen and apoptosis in the bovine interplacentomal uterine wall and foetal membranes. Anim Reprod Sci. 2006;91(1–2):55–76. doi:10.1016/j.anireprosci.2005.03.012.View ArticlePubMedGoogle Scholar
- Boos A, Stelljes A, Kohtes J. Collagen types I, III and IV in the placentome and interplacentomal maternal and fetal tissues in normal cows and in cattle with retention of fetal membranes. Cells Tissues Organs. 2003;174(4):170–83. doi:10.1159/000072720.View ArticlePubMedGoogle Scholar
- Shynlova O, Mitchell JA, Tsampalieros A, Langille BL, Lye SJ. Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium. Biol Reprod. 2004;70(4):986–92. doi:10.1095/biolreprod.103.023648.View ArticlePubMedGoogle Scholar
- Arens Y, Kamm KE, Rosenfeld CR. Maturation of ovine uterine smooth muscle during development and the effects of parity. J Soc Gynecol Investig. 2000;7(5):284–90.View ArticlePubMedGoogle Scholar
- Ipson MA, Rosenfeld CR, Magness RR, Kamm KE. Alterations in myometrial stress during ovine pregnancy and the puerperium. Am J Physiol. 1996;271(2 Pt 2):R446–54.PubMedGoogle Scholar
- Shynlova O, Tsui P, Dorogin A, Chow M, Lye SJ. Expression and localization of alpha-smooth muscle and gamma-actins in the pregnant rat myometrium. Biol Reprod. 2005;73(4):773–80. doi:10.1095/biolreprod.105.040006.View ArticlePubMedGoogle Scholar
- Walter I, Boos A. Matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitor-2 of matrix metalloproteinases (TIMP-2) in the placenta and interplacental uterine wall in normal cows and in cattle with retention of fetal membranes. Placenta. 2001;22(5):473–83. doi:10.1053/plac.2001.0633.View ArticlePubMedGoogle Scholar
- Schnorr B, Kressin M. Embryologie der Haustiere. 6th ed. Stuttgart: Enke; 2011.Google Scholar
- Böck P. Romeis Mikroskopische Technik. Munich: Urban and Schwarzenberg; 1989.Google Scholar
- Björkman N. Morphological studies on the epithelia of the intercotyledonary component of the bovine placenta. Acta Morphol Neerl Scand. 1956;1(1):41–51.PubMedGoogle Scholar
- Ulbrich SE, Frohlich T, Schulke K, Englberger E, Waldschmitt N, Arnold GJ, et al. Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen. Biol Reprod. 2009;81(4):795-805. doi:10.1095/biolreprod.108.075184.View ArticlePubMedGoogle Scholar
- Wooding FB, Fowden AL, Bell AW, Ehrhardt RA, Limesand SW, Hay WW. Localisation of glucose transport in the ruminant placenta: implications for sequential use of transporter isoforms. Placenta. 2005;26(8–9):626–40. doi:10.1016/j.placenta.2004.09.013.View ArticlePubMedGoogle Scholar
- Forde N, Spencer TE, Bazer FW, Song G, Roche JF, Lonergan P. Effect of pregnancy and progesterone concentration on expression of genes encoding for transporters or secreted proteins in the bovine endometrium. Physiol Genomics. 2010;41(1):53–62. doi:10.1152/physiolgenomics.00162.2009.View ArticlePubMedGoogle Scholar
- Nikitenko L, Morgan G, Kolesnikov SI, Wooding FB. Immunocytochemical and In situ hybridization studies of the distribution of calbindin D9k in the bovine placenta throughout pregnancy. J Histochem Cytochem. 1998;46(5):679–88.View ArticlePubMedGoogle Scholar
- Sprekeler N, Kowalewski MP, Boos A. TRPV6 and Calbindin-D9k-expression and localization in the bovine uterus and placenta during pregnancy. Reprod Biol Endocrinol. 2012;10:66. doi:10.1186/1477-7827-10-66.View ArticlePubMed CentralPubMedGoogle Scholar
- Awad M, Kizaki K, Takahashi T, Hashizume K. Dynamic expression of SOLD1 in bovine uteroplacental tissues during gestation. Placenta. 2013;34(8):635–41. doi:10.1016/j.placenta.2013.05.004.View ArticlePubMedGoogle Scholar
- Mishra B, Kizaki K, Koshi K, Ushizawa K, Takahashi T, Hosoe M, et al. Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its expected roles in the bovine endometrium during gestation. Domest Anim Endocrinol. 2012;42(2):63–73. doi:10.1016/j.domaniend.2011.09.004.View ArticlePubMedGoogle Scholar
- Froehlich R, Hambruch N, Haeger JD, Dilly M, Kaltner H, Gabius HJ, et al. Galectin fingerprinting detects differences in expression profiles between bovine endometrium and placentomes as well as early and late gestational stages. Placenta. 2012;33(3):195–201. doi:10.1016/j.placenta.2011.12.016.View ArticlePubMedGoogle Scholar
- Arosh JA, Banu SK, Chapdelaine P, Fortier MA. Temporal and tissue-specific expression of prostaglandin receptors EP2, EP3, EP4, FP, and cyclooxygenases 1 and 2 in uterus and fetal membranes during bovine pregnancy. Endocrinology. 2004;145(1):407–17. doi:10.1210/en.2003-1007.View ArticlePubMedGoogle Scholar
- Wehbrink D, Hassig M, Ritter N, Zerbe H, Bleul U, Boos A. Immunohistochemical demonstration of cyclooxygenase-2 (COX-2) and prostaglandin receptors EP2 and FP expression in the bovine intercaruncular uterine wall around term. Anim Reprod Sci. 2008;106(3–4):241–54. doi:10.1016/j.anireprosci.2007.04.016.View ArticlePubMedGoogle Scholar
- Schaubli M, Ritter N, Hassig M, Zerbe H, Bleul U, Boos A. Progesterone receptors, oestrogen receptor alpha and glucocorticoid receptors in the bovine intercaruncular uterine wall around parturition. Anim Reprod Sci. 2008;103(3–4):215–27. doi:10.1016/j.anireprosci.2006.12.015.View ArticlePubMedGoogle Scholar
- Kolle S, Sinowatz F, Boie G, Lincoln D, Waters MJ. Differential expression of the growth hormone receptor and its transcript in bovine uterus and placenta. Mol Cell Endocrinol. 1997;131(2):127–36.View ArticlePubMedGoogle Scholar
- Robinson RS, Mann GE, Gadd TS, Lamming GE, Wathes DC. The expression of the IGF system in the bovine uterus throughout the oestrous cycle and early pregnancy. J Endocrinol. 2000;165(2):231–43.View ArticlePubMedGoogle Scholar
- Leung ST, Wathes DC. Regulatory effect of steroid hormones and fetal tissues on expression of oxytocin receptor in the endometrium of late pregnant ewes. J Reprod Fertil. 1999;115(2):243–50.View ArticlePubMedGoogle Scholar
- Forde N, Mehta JP, McGettigan PA, Mamo S, Bazer FW, Spencer TE, et al. Alterations in expression of endometrial genes coding for proteins secreted into the uterine lumen during conceptus elongation in cattle. BMC Genomics. 2013;14:321. doi:10.1186/1471-2164-14-321.View ArticlePubMed CentralPubMedGoogle Scholar
- Schulz LC, Merkt H. Morphologische Befunde an extirpierten Plazentomen, zugleich ein Beitrag zur Ätiologie der Retentio secundinarum beim Rind. Monatsh Veterinarmed. 1956;11:712–4.Google Scholar
- Yamauchi S, Kotera K, Kakishita T. Histological study of the pregnant uterus in the cow. I. General histology of the endometrium of the intercaruncular area. Anim Sci J. 1956;39:487–504.Google Scholar
- Segerson EC, Bazer FW. High molecular weight basic and acidic immunosuppressive protein components in uterine secretions of pregnant cows. Biol Reprod. 1989;41(6):1014–23.View ArticlePubMedGoogle Scholar
- Leslie MV, Hansen PJ. Progesterone-regulated secretion of the serpin-like proteins of the ovine and bovine uterus. Steroids. 1991;56(12):589–97.View ArticlePubMedGoogle Scholar
- Leslie MV, Hansen PJ, Newton GR. Uterine secretions of the cow contain proteins that are immunochemically related to the major progesterone-induced proteins of the sheep uterus. Domest Anim Endocrinol. 1990;7(4):517–26.View ArticlePubMedGoogle Scholar
- Wathes DC, Reynolds TS, Robinson RS, Stevenson KR. Role of the insulin-like growth factor system in uterine function and placental development in ruminants. J Dairy Sci. 1998;81(6):1778–89. doi:10.3168/jds.S0022-0302(98)75747-9.View ArticlePubMedGoogle Scholar
- Kizaki K, Ushizawa K, Takahashi T, Yamada O, Todoroki J, Sato T, et al. Gelatinase (MMP-2 and −9) expression profiles during gestation in the bovine endometrium. Reprod Biol Endocrinol. 2008;6:66. doi:10.1186/1477-7827-6-66.View ArticlePubMed CentralPubMedGoogle Scholar
- Shynlova O, Chow M, Lye SJ. Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch. Reprod Sci. 2009;16(10):960–9. doi:10.1177/1933719109338220.View ArticlePubMedGoogle Scholar
- Shynlova O, Tsui P, Jaffer S, Lye SJ. Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour. Eur J Obstet Gynecol Reprod Biol. 2009;144 Suppl 1:S2–10. doi:10.1016/j.ejogrb.2009.02.044.View ArticlePubMedGoogle Scholar
- Taggart MJ, Morgan KG. Regulation of the uterine contractile apparatus and cytoskeleton. Semin Cell Dev Biol. 2007;18(3):296–304. doi:10.1016/j.semcdb.2007.05.006.View ArticlePubMed CentralPubMedGoogle Scholar
- Garfield RE, Maner WL. Physiology and electrical activity of uterine contractions. Semin Cell Dev Biol. 2007;18(3):289–95. doi:10.1016/j.semcdb.2007.05.004.View ArticlePubMed CentralPubMedGoogle Scholar
- Taverne MM, de Schwartz NC, Kankofer M, Bevers MM, van Oord HA, Schams D, et al. Uterine responses to exogenous oxytocin before and after pre-partum luteolysis in the cow. Reprod Domest Anim. 2001;36(5):267–72.View ArticlePubMedGoogle Scholar
- Fuchs AR, Fields MJ, Freidman S, Shemesh M, Ivell R. Oxytocin and the timing of parturition. Influence of oxytocin receptor gene expression, oxytocin secretion, and oxytocin-induced prostaglandin F2 alpha and E2 release. Adv Exp Med Biol. 1995;395:405–20.PubMedGoogle Scholar
- Fuchs AR, Rust W, Fields MJ. Accumulation of cyclooxygenase-2 gene transcripts in uterine tissues of pregnant and parturient cows: stimulation by oxytocin. Biol Reprod. 1999;60(2):341–8.View ArticlePubMedGoogle Scholar
- Slonina D, Kowalik MK, Kotwica J. Expression of progesterone receptor membrane component 1, serpine mRNA binding protein 1 and nuclear progesterone receptor isoforms A and B in the bovine myometrium during the estrous cycle and early pregnancy. J Reprod Dev. 2012;58(3):288–94.View ArticlePubMedGoogle Scholar
- Slonina D, Kowalik MK, Subocz M, Kotwica J. The effect of ovarian steroids on oxytocin-stimulated secretion and synthesis of prostaglandins in bovine myometrial cells. Prostaglandins Other Lipid Mediat. 2009;90(3–4):69–75. doi:10.1016/j.prostaglandins.2009.08.006.View ArticlePubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.