Messenger RNA Expression of Selected Factors at Different Sites of the Bovine Endometrium Associated With Uterine Health.

Recent studies have elucidated the role of several pro-inflammatory factors as mediators of inflammatory processes in the bovine endometrium. Only few studies, however, have analyzed samples collected from different regions of the uterus of the same animal. In this study, we tested the hypothesis that on a molecular level, clinical endometritis is characterized by inflammatory responses spread over the entire endometrium. Furthermore, we assume that subclinical endometritis is described by an inflammation of local regions of the uterus. Therefore, the objective of this study was to assess the mRNA expression of uterus-associated pro-inflammatory factors at five pre-defined endometrial sites, i.e., corpus uteri, left horn base, left horn tip, right horn base, and right horn tip, in cows with clinical and subclinical endometritis and in healthy controls. We analyzed the mRNA expression of interleukin 1 alpha, interleukin 1 beta, C-X-C motif chemokine ligand 8, prostaglandin-endoperoxide synthase 2, protein tyrosine phosphatase receptor type C, carcinoembryonic antigen related cell adhesion molecule 1, and mucin 4 and 16. Based on vaginoscopy and endometrial cytology (≥ 5% polymorphonuclear neutrophils) between 28 to 34 days in milk, 18 Simmental cows were categorized in clinical endometritis group (n = 7), subclinical endometritis group (n = 4), and healthy group (n = 7). In general, the analyses revealed a great variation of mRNA expression between sites and animals. Differences were found between different uterine health statuses, but the variation between the sampling sites within the groups was not significant (P > 0.05). This indicates that inflammatory processes at the end of the postpartum period can be regarded as multi-focal or spread throughout the uterus independent from the uterine health status.

Streptococcus uberis strains originating from bovine uteri provoke upregulation of pro-inflammatory factors mRNA expression of endometrial epithelial cells in vitro.

Streptococcus uberis is an opportunistic pathogen involved in various infections of cattle. It is a well-known etiological agent of bovine mastitis and has recently also been linked to postpartum endometritis in dairy cows. S. uberis is frequently isolated from the uterus of postpartum cows but its actual contribution to host pathophysiology is unknown and information on S. uberis virulence factors potentially involved in the disease is lacking. To gain first insights into the role of S. uberis in the pathology of bovine endometritis, a cell-culture-based infection model was employed to study inflammatory host responses and investigate cytotoxic effects. A comprehensive strain panel, comprising 53 strains previously isolated from bovine uteri, was compiled and screened for known virulence factor genes. Isolates showing distinct virulence gene patterns were used to study their impact on cellular viability and influence on mRNA expression of pro-inflammatory factors in endometrial epithelial cells. Our study revealed that S. uberis negatively impacts the viability of endometrial epithelial cells and provokes an upregulation of specific pro-inflammatory factors, although with certain strains having a greater effect than others. Especially, mRNA expression of IL1A and CXCL8 as well as CXCL1/2 and PTGS2 was found to be stimulated by S. uberis. These results suggest that S. uberis might indeed contribute to the establishment of bovine endometritis.

Formation of Surface Deposits on Steel and Titanium Aviation Fuel Tubes under Real Operating Conditions.

In this study, stainless steel and titanium (Ti) tubes obtained from a turbofan engine after the end of its lifetime were analyzed in order to compare the amount of pyrolytic coke present and its influence on the parent, base material. Various analytical techniques including microhardness and topographical evaluations, optical emission spectrometry (OES), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) were applied. On steel surfaces, a thick pyrolytic coke deposition layer consisting of carbon and oxygen and also containing elements from the tube material, fuel, and fuel additives was found. The concentration of elements from the pyrolytic coke continuously decreased with distance from the surface of the deposit, while the concentrations of elements from the tube material continuously increased, with the concentrations of elements from the fuel and the fuel additives being relatively constant. With ultrasonic cleaning in distilled water, most of the deposits could be removed. Only carbon-rich patches with a thickness of more than 300 nm remained adhered to the surface and/or had diffused into the original material. On Ti surfaces, the thickness of the C-rich fuel deposit layer was significantly thinner as compared to that on the stainless steel; however, the surface was covered with an ∼3 µm-thick oxide layer, which consisted of elements from the fuel additives. It is believed that the beneficial properties of Ti covered with a thin layer of TiO2, such as low adhesion and/or surface energy, have promoted different deposition mechanisms compared to those of stainless steel and thus prevented pyrolytic coke deposition and the related material deterioration observed on stainless steel.

Bovine Endometrial Epithelial Cells Scale Their Pro-inflammatory Response In vitro to Pathogenic Trueperella pyogenes Isolated from the Bovine Uterus in a Strain-Specific Manner.

Among different bacteria colonizing the bovine uterus, Trueperella pyogenes is found to be associated with clinical endometritis (CE). The ability of cows to defend against T. pyogenes infections depends on the virulence of invading bacteria and on the host's innate immunity. Therefore, to gain insights into bacterial factors contributing to the interplay of this host pathogen, two strains of T. pyogenes were included in this study: one strain (TP2) was isolated from the uterus of a postpartum dairy cow developing CE and a second strain (TP5) was isolated from a uterus of a healthy cow. The two strains were compared in terms of their metabolic fingerprints, growth rate, virulence gene transcription, and effect on bovine endometrial epithelial cells in vitro. In addition, the effect of the presence of peripheral blood mononuclear cells (PBMCs) on the response of endometrial epithelial cells was evaluated. TP2, the strain isolated from the diseased cow, showed a higher growth rate, expressed more virulence factors (cbpA, nanH, fimE, and fimG), and elicited a higher mRNA expression of pro-inflammatory factors (PTGS2, CXCL3, and IL8) in bovine endometrial epithelial cells compared with TP5, the strain isolated from the healthy cow. The presence of PBMCs amplified the mRNA expression of pro-inflammatory factors (PTGS2, CXCL3, IL1A, IL6, and IL8) in bovine endometrial epithelial cells co-cultured with live TP2 compared with untreated cells, especially as early as after 4 h. In conclusion, particular strain characteristics of T. pyogenes were found to be important for the development of CE. Furthermore, immune cells attracted to the site of infection might also play an important role in up-regulation of the pro-inflammatory response in the bovine uterus and thus significantly contribute to the host-pathogen interaction.

mRNA expression pattern of selected candidate genes differs in bovine oviductal epithelial cells in vitro compared with the in vivo state and during cell culture passages.

BACKGROUND: The mammalian oviduct provides the optimal environment for gamete maturation including sperm capacitation, fertilization, and development of the early embryo. Various cell culture models for primary bovine oviductal epithelial cells (BOEC) were established to reveal such physiological events. The aim of this study was to evaluate 17 candidate mRNA expression patterns in oviductal epithelial cells (1) in transition from in vivo cells to in vitro cells; (2) during three consecutive cell culture passages; (3) affected by the impact of LOW or HIGH glucose content media; and (4) influenced by different phases of the estrous cycle in vivo and in vitro. In addition, the release of a metabolite and proteins from BOEC at two distinct cell culture passage numbers was estimated to monitor the functionality. METHODS: BOEC from 8 animals were isolated and cultured for three consecutive passages. Total RNA was extracted from in vivo and in vitro samples and subjected to reverse transcription quantitative polymerase chain reaction to reveal mRNA expression of selected candidate genes. The release of prostaglandin E2 (PGE2), oviduct-specific glycoprotein 1 (OVGP1) and interleukin 8 (IL8) by BOEC was measured by EIA or ELISA after 24 h. RESULTS: Almost all candidate genes (prostaglandin synthases, enzymes of cellular metabolism and mucins) mRNA expression pattern differed compared in vivo with in vitro state. In addition, transcription of most candidate genes was influenced by the number of cell culture passages. Different glucose medium content did not affect mRNA expression of most candidate genes. The phase of the estrous cycle altered some candidate mRNA expression in BOEC in vitro at later passages. The release of PGE2 and OVGP1 between passages did not differ. However, BOEC in passage 3 released significantly higher amount of IL8 compared with cells in passage 0. CONCLUSION: This study supports the hypothesis that candidate mRNA expression in BOEC was influenced by transition from the in vivo situation to the new in vitro environment and during consecutive passages. The consequence of cell culture passaging on BOEC ability to release bioactive compounds should be considered.

Increased mRNA expression of selected pro-inflammatory factors in inflamed bovine endometrium in vivo as well as in endometrial epithelial cells exposed to Bacillus pumilus in vitro.

Endometrial epithelium plays a crucial role in the first immune response to invading bacteria by producing cytokines and chemokines. The aim of this study was to investigate the first inflammatory response of the endometrium in vivo and in vitro. Gene expression of several pro-inflammatory factors and Toll-like receptors (TLR2, -4, -6) was determined in endometrial cytobrush samples obtained from healthy cows and cows with clinical or subclinical endometritis. Endometrial epithelial cells were co-cultured with an isolated autochthonous uterine bacterial strain Bacillus pumilus. Total RNA was extracted from in vivo and in vitro samples and subjected to real-time reverse transcription polymerase chain reaction. CXC ligands (CXCL) 1/2 and CXC chemokine receptor (CXCR) 2 mRNA expression was higher in cows with subclinical endometritis and CXCL3 mRNA expression was higher in cows with clinical endometritis compared with healthy cows. B. pumilus induced cell death of epithelial cells within 24h of co-culturing. The presence of B. pumilus resulted in significantly higher mRNA expression of interleukin 1α (IL1A), IL6, IL8, CXCL1-3 and prostaglandin-endoperoxide synthase 2 in co-cultured cells compared with untreated controls. The maximum increase was mainly detected after 2h. These results support the hypothesis that bacterial infection of endometrial cells might induce prompt synthesis of pro-inflammatory cytokines resulting in a local inflammatory reaction.

Detection and characterisation of Lactobacillus spp. in the bovine uterus and their influence on bovine endometrial epithelial cells in vitro.

Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro-inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals) were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively). Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h) total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL) IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F(2α) in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties.

Identification of differentially expressed proteins in ruminal epithelium in response to a concentrate-supplemented diet.

Ruminal epithelium adapts to dietary change with well-coordinated alterations in metabolism, proliferation, and permeability. To further understand the molecular events controlling diet effects, the aim of this study was to evaluate protein expression patterns of ruminal epithelium in response to various feeding regimes. Sheep were fed with a concentrate-supplemented diet for up to 6 wk. The control group received hay only. Proteome analysis with differential in gel electrophoresis technology revealed that, after 2 days, 60 proteins were significantly modulated in ruminal epithelium in a comparison between hay-fed and concentrate-fed sheep (P < 0.05). Forty proteins were upregulated and 20 proteins were downregulated in response to concentrate diet. After 6 wk of this diet, only 14 proteins were differentially expressed. Among these, 11 proteins were upregulated and 3 downregulated. To identify proteins that were modulated by dietary change, two-dimensional electrophoresis was coupled with liquid chromatography electrospray ionization mass spectrometry. The differential expression of selected proteins, such as esterase D, annexin 5, peroxiredoxin 6, carbonic anhydrase I, and actin-related protein 3, was verified by immunoblotting and/or mRNA analysis. The identified proteins were mainly associated with functions related to cellular stress, metabolism, and differentiation. These results suggest new candidate proteins that may contribute to a better understanding of the signaling pathways and mechanisms that mediate rumen epithelial adaptation to high-concentrate diet.

Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum.

BACKGROUND: Inflammatory processes and infections of the uterine wall must be accepted as a physiological event in dairy cows after calving. This might result in clinical or subclinical endometritis which is assumed to impair reproductive performance in the current lactation. Several cytokines and acute phase proteins have been discussed as local and systemic mediators of these inflammatory processes. The aim of the present study was to investigate the endometrial mRNA expression of the chemokine CXC ligand 5 (CXCL5), interleukin 1ß (IL1B), IL6, IL8, tumour necrosis factor alpha (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2) and haptoglobin (HP) in the postpartum period. METHODS: Endometrial samples were obtained from primiparous cows (n = 5) on days 10, 17, 24, 31, 38 and 45 postpartum (pp) using the cytobrush technique. Cytological smears were prepared from cytobrush samples to determine the proportion of polymorphonuclear neutrophils (PMN). Total RNA was extracted from endometrial samples, and real-time RT-PCR was performed. RESULTS: A time-dependent mRNA expression of the investigated factors was found for the course of the postpartum period. In detail, a significantly higher expression of these factors was observed on day 17 pp compared to day 31 pp. Furthermore, the proportion of PMN peaked between days 10-24 pp and decreased thereafter to low percentages (< 5%) on day 31 pp and thereafter. In addition, CXCL5, IL1B, IL8 and HP mRNA expression correlated significantly with the proportion of PMN (P < 0.05). A significantly higher CXCL5, IL1B, IL6, IL8, PTGS2 and TNF mRNA content was observed in samples from cows with an inflamed endometrium compared with samples from cows with a healthy endometrium (P < 0.05). CONCLUSIONS: These results show that inflammatory cytokines and acute phase proteins are expressed in the bovine endometrium in a time-related manner during the postpartum period, with a significant expression peak on day 17 pp as a possible mucosal immune response in the uterus. The evaluation of the expression patterns of such candidate genes may reveal more information than only determining the percentage of PMN to judge the severity of an inflammation.

Selected pro-inflammatory factor transcripts in bovine endometrial epithelial cells are regulated during the oestrous cycle and elevated in case of subclinical or clinical endometritis.

Endometrial cells take part in embryo-maternal communication, as well as supporting the immune system in defending against invading pathogens. The aim of the present study was to examine the mRNA expression of factors that have been suggested to be involved in both events in the bovine endometrial epithelium, namely bovine granulocyte chemotactic protein 2 (CXCL5), interleukin-1 beta (IL1B), IL6, IL8, tumour necrosis factor (TNF), cyclooxygenase 2 (PTGS2) and haptoglobin (HP). Samples were collected in vivo from cows on Days 21-27 postpartum by the cytobrush method to evaluate the correlation between inflammatory factors and uterine health (cows with signs of clinical or subclinical endometritis and healthy cows). Bovine uteri were collected at the abattoir to investigate oestrous cycle-dependent mRNA expression patterns. Real-time reverse transcription-polymerase chain reaction revealed that the expression of CXCL5, IL1B, IL8 and TNF mRNA was significantly higher in cows with subclinical or clinical endometritis compared with healthy cows. The expression of CXCL5, IL1B and IL8 mRNA was increased around ovulation compared with the luteal phase. There was no indication of either oestrous cycle-dependent expression or a correlation with uterine health for IL6, PTGS2 and HP transcripts. These results suggest that CXCL5, IL1B, IL8 and TNF may represent potential marker genes for the detection of cows with subclinical endometritis and for monitoring new therapeutic approaches.

Vascular endothelial growth factor A is a putative paracrine regulator in seasonally controlled spermatogenesis: insights from a ruminant model, the roe deer.

Vascular endothelial growth factor A (VEGFA) influences spermatogenesis, but its impact on seasonally regulated sperm production is still not fully understood. Thus, we investigated both expression levels and localisation of VEGFA and its receptors VEGFR1 and 2 in roe buck testis via real-time reverse transcription polymerase chain reaction and immunohistochemistry in relation to seasonal changes in the cellular composition of the testis. VEGFA was expressed by interstitial cells while its receptors were found on endothelial and perivascular cells. Inside the tubules, VEGFA was located in spermatogonia and spermatocytes, VEGFR1 was present on elongating spermatids and VEGFR2 on Sertoli cells. VEGFR1 mRNA was expressed tenfold lower than VEGFR2 and VEGF mRNAs. Relative VEGF and VEGFR2 expression (divided by the number of VEGFA and VEGFR2 expressing cells) showed an increase towards the rut (July/August) and a decrease thereafter. The results suggest involvement of VEGFA in the adjustment of vascular permeability as well as in spermiogenesis and the proliferation of spermatogonia.

Intestinal expression of TFF and related genes during postnatal development in a piglet probiotic trial.

Trefoil factor family (TFF) peptides provide protective and reparative effects by enhancing epithelial integrity and promoting mucosal restitution. TFF peptide expression is induced after mucosal damage. These processes are of central physiological relevance during the postnatal intestinal development and are strongly influenced during the weaning period. In piglets, weaning at early maturation stages frequently causes mucosal inflammation. The aim of this study was to evaluate postnatal intestinal TFF expression in a piglet probiotic trial. Low intestinal TFF2 expression was measured at early maturation stages. Weaning, however, was associated with a distinct response of increased TFF2 expression, indicating an important role in enhancing mucosal integrity. In the distal jejunum and ileum weaning could as well be associated with increased TFF3 mRNA levels. Differential TFF1 expression was not detected. Furthermore, TFF2 localization studies in different intestinal loci were performed by means of immunohistochemistry. Expression of selected genes (TGFA, EGFR, Cox-2) known to promote TFF signaling showed differential expression pattern as well, thereby providing further functional background. Furthermore, the expression patterns of EGFR observed in this study contribute to an advanced view of previous findings of EGFR regulation mainly obtained in rodents. An upregulated EGFR expression during early postnatal development suggests a local relevance to porcine intestinal maturation. However, a feed supplementation with the probiotic strain Enterococcus faecium did not influence TFF expression.

Interleukin-4 supports interleukin-12-induced proliferation and interferon-gamma secretion in human activated lymphoblasts and T helper type 1 cells.

Interleukin-12 (IL-12) and IL-4 are known to differentially promote T helper (Th) cell differentiation. While IL-12 induces interferon-gamma (IFN-gamma) production and maturation of Th1 cells, IL-4 is thought to antagonize IL-12 and to favour Th2 development. Here we studied the combined action of various concentrations of common gamma-chain (gamma(c)-chain) cytokines, including IL-4 and the Th1 cytokine IL-12, in human activated lymphoblasts and Th1 cells. IL-4 and IL-7 potentiated IL-12-induced proliferation at every concentration tested (1-10 ng/ml) without increasing rescue from apoptosis, indicating that proliferation was directly affected by these cytokine combinations. With regards to cytokine secretion, IL-2 together with IL-12 initiated tumour necrosis factor-alpha synthesis, enhanced IFN-gamma production, and shedding of soluble IL-2 receptor alpha as expected. Importantly, combining IL-4 with IL-12 also enhanced IFN-gamma secretion in lymphoblasts and a Th1 cell line. Investigating signal transduction in lymphoblasts induced by these cytokines, we found that not only IL-2 but also IL-4 enhances signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation by IL-12. Tyrosine phosphorylations of janus kinase 2 (JAK-2), tyrosine kinase 2 (TYK2), extracellular signal-regulated kinase (ERK) and STAT4, STAT5 and STAT6 were not potentiated by combinations of these cytokines, suggesting specificity for increased STAT3 phosphorylation. In conclusion, two otherwise antagonizing cytokines co-operate in activated human lymphoblasts and Th1 cells, possibly via STAT3 as a converging signal. These data demonstrate that IL-4 can directly enhance human Th1 cell function independently of its known actions on antigen-presenting cells. These findings should be of importance for the design of cytokine-targeted therapies of human Th-cell-driven diseases.

[Postpartum reproductive failure in cattle: is the examination of gene expression in the endometrium a key to success?]. / Postpartale Fruchtbarkeitsstörungen beim Rind: Untersuchung der Genexpression im Endometrium als Schlüssel zum Erfolg?

High reproductive performance is required for successful management of dairy farms. After calving, especially endometritis is one of the main reasons for reproductive failure. However, subclinical endometritis remains undetected in many cases and causes a high financial loss. To elucidate the cellular processes in the endometrium, the acquisition of the gene expression will provide helpful information. In the literature, numerous cytokines and enzymes were discussed to play important roles in preparing the endometrium for implantation. This review gives an overview about our present understanding of the functions of cyclooxygenases 1 and 2 (COX-1/COX-2), tumor necrosis factor alpha (TNFalpha), the inducible nitric oxide synthase (iNOS), haptoglobin as well as the interleukins 1 and 6 (IL-1/IL-6). Their role is not only to regulate certain physiological processes in the bovine reproductive tract, but to act also as inflammatory mediators in infectious diseases. A better understanding of cellular processes may help to improve identification and treatment of postpartum reproductive failure.

Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II.

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

Tumor necrosis factor alpha in the bovine oviduct during the estrous cycle: messenger RNA expression and effect on secretion of prostaglandins, endothelin-1, and angiotensin II.

Tumor necrosis factor (TNF) alpha is an important physiological mediator of cell-to-cell communication. Recent observations suggest that TNFalpha is involved in the control of reproductive functions. The present study examined the role of TNFalpha in the secretion of factors involved in regulating smooth muscle contraction, such as prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), endothelin-1 (ET-1), and angiotensin II (Ang II), as it was in the original by the cow oviduct at different stages of the estrous cycle using an in vitro microdialysis system. Expression of mRNA for TNFalpha and its receptors (TNFalpha-R) was also evaluated. For microdialysis, the lumen of a portion (length, 10 cm) of the each oviductal segment was implanted with a dialysis capillary membrane, and TNFalpha (100 ng/ml) was infused for 4-8 h during a 16-h incubation period. The microdialysis system maintains cell-to-cell integrity and cell-to-cell communication, and it enables real-time observation of physiological changes in the luminal release of different substances. Concentrations of PG, ET-1, and Ang II in 4-h fractions were measured using second-antibody enzyme immunoassays. Infusion of TNFalpha stimulated oviductal secretion of PG, ET-1, and Ang II during the follicular and postovulatory stages, but not during the luteal stage. Expression of TNFalpha, TNFalpha-R type I, and TNFalpha-R type II mRNA was detected in the bovine oviduct by reverse transcription-polymerase chain reaction. High expression of both TNFalphaR types and ligands was detected during the follicular and postovulatory stages, whereas low expression was detected during the luteal stage. The results of the present study provide, to our knowledge, the first direct evidence that TNFalpha stimulates PG, ET-1, and Ang II secretion and that up-regulation of the TNFalpha system occurs in the cow oviduct during the periovulatory period. In conclusion, the TNFalpha system may optimize the release of contraction-related substances and modulate local contraction to regulate the oviductal transport of the gametes and embryo.