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Reproductive problems in cattle are frequent and have an important impact on production. In addition, inflammatory, traumatic and other diseases may be followed by the development of tumours, which are a cause of culling of breeding males. The main types of tumours diagnosed in the bull penis are fibropapilloma and squamous cell carcinoma. The aim of this study was to characterize a case of a tumour in the glans penis of a bull from a dairy farm in Santa Fe, Argentina. The neoplastic tissue was stained with haematoxylin and eosin and then analysed by immunohistochemistry to reveal its characteristic phenotype. Results showed positivity to vimentin, neuron specific enolase, proliferating cell nuclear antigen, S100 and glial fibrillary acidic protein. This suggested that the tumour was a neoplasm of neural origin, classified as neurofibrosarcoma, a peripheral nerve sheath tumour, here reported in the penis of a bull for the first time., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship of publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim was to evaluate the effect of ACTH on the mechanisms involved in peripheral blood mononuclear cells (PBMCs) infiltration into the ovary during dairy cattle proestrus. Regarding this, proper expression pattern of adhesion molecules must take place both in PBMCs and in endothelial cells. Argentinian Holstein cows (n = 12) were treated with 100 IU of ACTH every 12 h for 4 days before ovulation when ovariectomy was performed (day 18). Blood samples were taken on day 15 (0 h) and immediately before (72 h) and after (74 h) the last ACTH administration. In PBMCs, flow cytometry was performed to analyze CD44, CD11b and CD62-L expression along with gene expression of chemokines' receptors. Interleukin (IL)-4 and tumor necrosis factor-α (TNF-α) production was analyzed by flow cytometry after exposing PBMCs to autologous follicular fluid. In ovarian blood vessels, expression of the vascular endothelium cell adhesion-1 (VCAM-1) and the platelet endothelial cell adhesion molecule-1 was evaluated by immunohistochemistry. In T-lymphocytes, the expression of CD44 and CD11b was lower at 72 h in ACTH-treated cows (P < 0.05). In monocytes, the expression of CD11b and CD62-L was lower at 72 h in ACTH-treated cows (P < 0.05). Also, the percentage of IL-4 + cells was higher in ACTH-treated cows, meanwhile, the percentage TNF-α + cells was lower in ACTH-treated cows (P < 0.05). Finally, in the vessels associated with the preovulatory follicle VCAM-1 immunoexpression was lower in ACTH-treated cows (P < 0.05). Here, we present novel insights into the effect of stress during the preovulatory period on the inflammatory pathway necessary for ovulation., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge., (© 2023. Springer Nature Limited.)

Before ovulation, the ovary exhibits signs of local inflammation. However, the effects of adrenocorticotropin (ACTH) on the complexity of this inflammatory response are not yet well described. Thus, the aim of this study was to evaluate the effects of ACTH administered to dairy cows during the preovulatory period on the local distribution of different subsets of leukocytes infiltrated in the ovary, along with the gene expression of relevant chemokines (C-C motif chemokine ligand-2 (CCL2), C-X-C motif chemokine ligand-8 (CXCL8), CCL25 and CXCL1) involved in leukocyte chemotaxis and blood perfusion on the follicular wall of dominant follicles. Also, the direct effect of ACTH on chemokine gene expression was addressed in cultured antral follicular walls. For this purpose, both an in vivo and an in vitro experiment were performed. For the in vivo experiment, exogenous ACTH (100 IU) was administered intramuscularly to Holstein cows (n = 12) during proestrus every 12 h for four days before ovulation, when ovariectomy was performed (day 18). Daily ovarian Doppler ultrasonography was used to evaluate the percentage of irrigated area, the pulsatility index and the resistance index in the dominant follicles. The distribution of monocytes-macrophages (CD14), T- (CD2) and B-lymphocytes (CD79a) and granulocytes (CH138A) in the ovary was analyzed by immunohistochemistry. In follicular wall samples, gene expression of CCL2, CXCL8, CXCL1 and CCL25 was evaluated, whereas IL-17A expression was analyzed by Western blot. The total number of CD14, CD79a and CD2 infiltrated cells was lower in the ACTH-treated group than in the control group (p < 0.05). Chemokine gene expression showed lower mRNA of CCL2, CCL25 and CXCL1 (p < 0.05) in the ACTH-treated group. Meanwhile, IL-17A protein expression and hemodynamic parameters were similar between groups (p > 0.05). In the in vitro assay, antral follicular walls were stimulated with ACTH to corroborate the gene expression profile of chemokines. mRNA expression of CCL2 tended to be lower in the stimulated follicular walls (p = 0.092). Our results suggest that exogenous ACTH stimulus during the preovulatory period reduces the number of infiltrated leukocytes in the bovine ovary and this could be due to a lower chemotaxis capacity of the ovary., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The objective of this study was to describe a case of a granulosa cell tumour (GCT) of incipient formation and to characterize it by its immunohistochemical pattern and hormonal profile. The case presented corresponds to a 7-year-old Holstein cow without reproductive disorders. No alterations were observed at rectal palpation, neither in the ultrasonography nor in the hormonal profile. A GCT concomitant with normal follicular development was diagnosed. Through a panel of immunohistochemical markers, a highly differentiated pattern could be determined in the GCT, which preserves the expression of steroid receptors (ESR1, ESR2 and PR) typical of granulosa cells, but does not express the enzymes for the synthesis of androgens (CYP17A1) and oestrogens (CYP19A1). In addition, the expression of co-regulators of steroid hormone receptors and neuroendocrine markers was described for the first time in a GCT in cattle. These results increase the information about GCTs in cattle before the ovarian function is compromised., (© 2021 Wiley-VCH GmbH.)

We describe the functional capability of a cross-linked hydrogel composed of sulfated glycosaminoglycans and a cationic cellulose by conducting trials on experimental animal models using intra-articular implants to treat an articular disease called osteoarthritis. Forty-eight mature New Zealand white rabbits were divided into three experimental groups: A, B, and C. Group A and B underwent unilateral anterior cruciate ligament transection (ACLT) of the right knee. Subsequently, both knees of group A were treated with the injectable formulation under study. Meanwhile, group B was treated with sterile PBS (placebo). The animals of group C were surgically operated in both knees: Commercial hyaluronic acid (HA) was implanted in the left knee, and the formulation under study was implanted in the right knee. After implantation, all specimens underwent several evaluations at 3, 6, and 12 months postoperatively. At 6 months, no significant differences were detected between the right and left knees of the different groups. However, significant differences were observed between both knees at 12 months in group C, with less cartilage damage in the right knees implanted with our hydrogel. Therefore, in vivo studies have demonstrated hydrogel safety, superior permanence, and less cartilage damage for long-term follow up 12 months after implantation for the formulation under study compared with commercial HA.

Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, reducing fertility by interfering with the mechanisms that regulate the timing of events within the follicular phase of the estrous cycle. In the HPA axis, melanocortin 2 receptor (MC2R) mediates responses to adrenocorticotropic hormone (ACTH) in concert with melanocortin receptor accessory protein 2 (MRAP2). The aims of the present study were: (1) to evaluate the effects of ACTH administered in cows in the preovulatory period on the expression of the MC2R/MRAP2 complex in the dominant follicle; and (2) to analyze the involvement of Extracellular signal Regulated Kinase 1 (ERK1) signaling in the activation of MC2R and the expression of key enzymes involved in the biosynthesis of glucocorticoids (GCs) in the dominant follicle. To this end, 100 IU ACTH was administered to Holstein cows from a local dairy farm during pro-estrus every 12 h for four days until ovariectomy, which was performed before ovulation. Protein immunostaining of MC2R was higher in the dominant follicles of ACTH-treated cows (p < 0.05). Also, Western blot analysis showed higher activation of the ERK1 signaling pathway in ACTH-treated cows (p < 0.05). Finally, immunohistochemistry performed in the dominant follicles of ACTH-treated cows detected higher expression of CYP17A1 and CYP21A2 (p < 0.05). These results suggest that the bovine ovary is able to respond locally to ACTH as a consequence of stress altering the expression of relevant steroidogenic enzymes. The results also confirm that the complete GC biosynthesis pathway is present in bovine dominant follicle and therefore GCs could be produced locally., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cattle undergo numerous environmental and management stressors that reduce fertility and affect ovulation. The extracellular matrix of the follicle wall can be altered by matrix metalloproteinases (MMPs), the activities of which are regulated by interleukins and tissue-specific inhibitors of metalloproteinases (TIMPs), especially during ovulation. The aims of the present study were to: (1) evaluate changes in the hormone milieu, the localisation and activity of MMP2 and MMP9 and the localisation of MMP14, TIMP1 and TIMP2 in response to adrenocorticotrophic hormone (ACTH) during the preovulatory period in cows; and (2) determine the direct effects of ACTH on the mRNA expression of MMP2 and MMP9 in the cultured follicle wall of bovine ovaries obtained from an abattoir. 100IU ACTH was administered during pro-oestrus every 12h until ovariectomy, which was performed before ovulation. Cortisol concentrations in the plasma and follicular fluid (FF) of preovulatory follicles were higher in ACTH-treated than control cows. Progesterone presented subluteal concentrations in plasma of ACTH-treated cows (P<0.05). MMP2 immunostaining and activity in ovaries were higher in ACTH-treated than control cows (P<0.05), whereas MMP9 immunostaining was similar between the two groups. However, unlike in control cows, MMP9 activity was absent in the FF of ACTH-treated cows. These results suggest that the administration of ACTH during the preovulatory period in cows could cause changes that culminate in modifications in the content and activation of MMPs and TIMPs in the ovary, which could interfere with the ovulation process.

Cystic ovaries (CO) characterize a disorder frequently found in dairy cattle. However, despite the contributions by several researchers, the mechanism that leads to ovulatory failure has not yet been completely elucidated. Thus, the aim of this study was to examine the mRNA expression of bovine vascular endothelial growth factor (VEGFA)-164, VEGFA-164b and VEGF receptors (VEGFR1 and VEGFR2) by real-time PCR and protein expression by immunohistochemistry, immunofluorescence and Western blot in follicular fluid from dairy cows with spontaneous CO and in an experimental model of follicular persistence induced by prolonged treatment with progesterone. Results showed that both VEGFA isoforms and receptors were coexpressed in granulosa and theca interna cells and in follicular fluid of ovaries from all the groups evaluated. VEGFA-164, VEGFA-164b and VEGFR2 protein expression was higher in theca cells of persistent follicles from group P0 (expected time of ovulation) than in those from dominant follicles (as reference structure) from the control group (p < 0.05). Also, VEGFA-164 expression was higher in theca cells of cysts than in those of dominant follicles of the control group (p < 0.05). In follicular fluid, VEGFA-164 expression was higher in persistent follicles from group P5 (5 days of follicular persistence) than in the control, P0 and P15 groups, and higher in cysts than in dominant follicles from the control group (p < 0.05). This study provides evidence of an altered expression of VEGFA-164, VEGFA-164b and VEGFR2 during the formation of persistent follicles and cysts in cows. Together, these results evidence that early development of CO in cows is concurrent with an altered expression of these growth factors and that these alterations may contribute to the follicular persistence, angiogenic dysregulation and ovulatory failure found in cows with follicular cysts., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A common reproductive disease in dairy cattle is Cystic Ovarian Disease. To study its development, there was use of an experimental model of follicular persistence to detect hemodynamic changes occurring in ovaries by using Doppler ultrasonography. After estrous synchronization, control cows received no additional treatment and were evaluated at proestrus (CG), whereas treated cows (PG) received sub-luteal doses of progesterone for 15 days and were evaluated at proestrus, and after 0, 5, 10 and 15 days of follicular persistence. Spectral Doppler was used to evaluate blood flow in the ovarian artery, and power Doppler for evaluation of blood flow in the ovarian parenchyma and follicular wall of persistent and dominant preovulatory follicles. Findings using power Doppler signals indicated there were no differences between groups in the parenchyma of both right (P =  0.455) and left (P =  0.762) ovaries. In contrast, power Doppler signals of blood flow were less in walls of persistent follicles from day 0 to 15 when there was follicular persistence than in dominant follicles of the CG (P <  0.001). Blood flow in ovarian arteries was less (P <  0.05) in diastolic velocity and time averaged maximum velocity in all PG groups than in the CG. Peak systolic velocity was less (P <  0.05) in all PG than in the CG, with the exception of P15 (P >  0.05). These findings indicate there are marked changes in blood irrigation area of walls of persistent follicles during the 15 days of follicular persistence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The objective of this study was to examine the expression of transforming growth factor beta receptor (TGFBR)1, TGFBR2, TGFBR3, activin receptor (ACVR)1B and ACVR2B in ovaries of cows with cystic ovarian disease (COD). The expression of the selected receptors was determined by immunohistochemistry in sections of ovaries from cows with ACTH-induced and spontaneous COD. Expression of TGFBR1 and TGFBR3 was higher in granulosa cells of cysts from cows with spontaneous COD than in tertiary follicles from the control group. Additionally, TGFBR3 expression was higher in granulosa cells of cysts from cows with ACTH-induced COD than in those from the control group and lower in theca cells of spontaneous and ACTH-induced cysts than in tertiary control follicles. There were no changes in the expression of TGFBR2. ACVR1B expression was higher in granulosa cells of tertiary follicles of cows with spontaneous COD than in the control group, whereas ACVR2B expression was higher in cysts of the spontaneous COD group than in tertiary follicles from the control group. The alterations here detected, together with the altered expression of the ligands previously reported, indicate alterations in the response of the ligands in the target cells, modifying their actions at cellular level., (© 2018 Blackwell Verlag GmbH.)

Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. The main signs of this infertility are ovulation failure and follicular persistence. The aim of this study was to examine the expression of the cytokines IL-1β, IL-1RI, IL-1RII, IL-1RA and IL-4 in ovarian follicular structures at different times of persistence in a model of follicular persistence induced by prolonged administration of progesterone in dairy cows. Protein expression of IL-1β, IL-1RI, IL-1RII, IL-1RA and IL-4 was evaluated by immunohistochemistry. Additionally, IL-1β and IL-4 concentrations in follicular fluid and serum were determined by ELISA. In granulosa cells, IL1-RII and IL-4 expression was higher in follicles with different persistence times than in the control dominant follicles. IL-1RA expression was higher in persistent follicles of the P15 group (15 days of follicular persistence) than in those of the control group. In theca cells, IL-1RII expression was higher in persistent follicles of the P0 group (expected time of ovulation) than in dominant follicles from the control group (p < .05) and the other persistence groups, whereas IL-4 expression was higher in persistent follicles of groups P0 and P15 than in the dominant follicles of the control group (p < .05). Differences between serum and follicular fluid within each group were detected only in P0 for IL-1β, and in the control, P10 and P15 groups for IL-4 (p < .05). These results complement previous results, evidencing that early development of COD in cows is concurrent with an altered expression of cytokines in different ovarian follicular structures and may contribute to the follicular persistence and ovulation failure found in cattle with follicular cysts., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein expressed exclusively in the gonads. This hormone is an important regulator of the early growth of follicles through inhibitory effects on the recruitment of primordial follicles into the pool of growing follicles and on granulosa cell proliferation. Cystic ovarian disease (COD) is an important disorder affecting the fertility of dairy cattle. In the present study, we evaluated the expression of AMH in granulosa cells and AMH secretion into follicular fluid in pre-ovulatory follicles from control cows, animals with spontaneously arising COD and during the development of the disease, at 5, 10 and 15 days of follicular persistence. To this end, after an oestrous synchronization protocol, low doses of progesterone was administered for 5, 10 and 15 days after the expected day of ovulation (day 0 of follicular persistence) in treated cows (groups P5, P10 and P15, respectively), using an intravaginal progesterone-releasing device. Results showed a decrease in the expression of AMH in granulosa cells throughout folliculogenesis (P <0.05) and in the spontaneously arising follicular cysts and persistent follicles related to the control group (P <0.05). There was also a higher concentration of AMH in the follicular fluid of persistent follicles at 10 and 15 days of follicular persistence (P <0.05). Together, these results may indicate an alteration in AMH expression and secretion, which occurs early in folliculogenesis and incipiently during the development of COD, and which could contribute to the recurrence of this disease in cattle., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In dairy cattle, cystic ovarian disease (COD) is an important cause of subfertility, and two of the main signs are ovulation failure and follicular persistence. The aim of this study was to examine the expression of the cytokines IL-1α, IL-6, IL-8 and TNF-α in ovarian follicular structures at different times of persistence in a model of follicular persistence induced by prolonged treatment with progesterone in dairy cows. Protein expression of IL-1α, IL-6, IL-8 and TNF-α was evaluated by immunohistochemistry. Additionally, IL-6 concentration in follicular fluid and serum was determined by ELISA. IL-1α, IL-6, IL-8 and TNF-α expression was increased in follicles with different persistence times in relation to the control dominant follicles, in granulosa cells. For IL-6, IL-8 and TNF-α, this increase was detected early (P0: expected time of ovulation and/or P5: 5 days of follicular persistence). Additionally, theca cells showed an increase in IL-6 in antral (groups P10 and P15) and persistent follicles (group P10) related to dominant follicles from the control group (p < 0.05). Serum concentration of IL-6 was higher in groups P5, P10 and P15 than in control cows (p < 0.05). The results show evidence that early development of COD in cows is concurrent with altered expression of these cytokines in different ovarian follicular structures and may contribute to the follicular persistence and endocrine changes found in cattle with follicular cysts., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Glucocorticoids (GCs) such as cortisol and corticosterone are important steroid hormones with different functions in intermediate metabolism, development, cell differentiation, immune response and reproduction. In response to physiological and immunological stress, adrenocorticotropic hormone (ACTH) acts on the adrenal gland by stimulating the synthesis and secretion of GCs. However, there is increasing evidence that GCs may also be synthesized by extra-adrenal tissues. Here, we examined the gene and protein expression of the enzyme 11β-hydroxylase P450c11 (CYP11B1), involved in the conversion of 11-deoxycortisol to cortisol, in the different components of the bovine ovary and determined the functionality of CYP11B1 in vitro CYP11B1 mRNA was expressed in granulosa and theca cells in small, medium and large antral ovarian follicles, and CYP11B1 protein was expressed in medium and large antral follicles. After stimulation by ACTH, we observed an increased secretion of cortisol by the wall of large antral follicles. We also observed a concentration-dependent decrease in the concentration of cortisol in response to metyrapone, an inhibitor of CYP11B1. This decrease was significant at 10 -5  µM metyrapone. In conclusion, this study demonstrated for the first time the presence of CYP11B1 in the bovine ovary. This confirms that there could be a local synthesis of GCs in the bovine ovary and therefore a potential endocrine responder to stress through these hormones., (© 2017 Society for Reproduction and Fertility.)

The most important regulators of tissue remodelling during ovarian follicular growth, development, ovulation and atresia are gonadotropins, steroid hormones, growth factors and different proteolytic enzymes. Matrix metalloproteinases (MMPs) such as collagenase or gelatinase (i.e. MMP-1, -8, -2 and -9) and associated tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) control connective tissue remodelling during follicular rupture. In this study, we hypothesized that an imbalance in the MMP-TIMP system may be an intra-ovarian component that contributes to the pathogenesis of cystic ovarian disease (COD) in cows. Taking into account that the control of MMP activity by TIMPs could determine their effects in both physiological and pathological conditions, MMP and TIMP mRNA and protein expression was examined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively, in ovaries from control cows and cows with COD. Expression of mRNA encoding MMP-2, TIMP-1 and TIMP-2 was lower in follicular cysts than in control pre-ovulatory follicles, while the results by IHC showed this imbalance only for TIMP-2 protein expression. Additional analysis by zymography to evaluate the gelatinase activity of MMP-2 and MMP-9 demonstrated higher MMP-2 activity in follicular fluid (FF) of cysts than in FF of pre-ovulatory follicles. On the other hand, MMP-9 activity was increased in follicular cysts and absent in the FF of pre-ovulatory follicles. These findings suggest that the altered mRNA expression and activities of the MMP-TIMP system may be related to the failure in ovulation and follicular development observed in COD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The objective of this work was to evaluate proliferation and apoptosis in the bovine ovary in a model of follicular persistence induced by low levels of progesterone to detect incipient changes during cystic ovarian disease development on the expected day of ovulation (day 0) and after 5, 10, and 15 days of follicular persistence. We analyzed cell proliferation by evaluating the expression of Ki-67 and apoptosis by evaluating caspase-3, BAX, and BCL2 expression. Proliferation was similar in the granulosa and theca cells of antral follicles in the P0 group (treated with progesterone up to the expected day of ovulation) and in the control group. A decrease in cell proliferation was detected after 5 days of persistence (P5) in relation to P0 (p < 0.05). Similar changes were found in the granulosa cells of the persistent follicles in relation to the control group (p < 0.05). Caspase-3 expression was similar in granulosa cells of antral follicles at early stages of persistence, with an increase after 15 days of persistence (p < 0.05). In the granulosa cells of group P10 (10 days of persistence), caspase-3 expression was reduced relative to that of antral follicles from the control group (p < 0.05). BCL2 expression was higher in granulosa cells of the persistent follicles of group P0 relative to the control follicles, with no changes in BAX expression, which was increased in persistent follicles of group P15 (p < 0.05). Similar results were observed in theca cells at initial stages of persistence. The results show that, initially, proliferation is maintained with low apoptosis and an increase in cell survival., (© 2017 S. Karger AG, Basel.)

Cystic ovarian disease (COD) is an important cause of subfertility in dairy cattle. Bone morphogenetic proteins (BMPs), mainly BMP2, BMP4 and BMP6, play a key role in female fertility. In this study, we hypothesized that an altered BMP system is associated with ovarian alterations contributing to COD pathogenesis. Therefore, we examined the expression of BMP2, BMP4 and BMP6 and BMP receptor 1B (BMPR1B) in the ovaries of animals with spontaneous or ACTH-induced COD, as well as during the development of the disease, in a model of follicular persistence induced by low doses of progesterone (at 5, 10 and 15 days of follicular persistence). Results showed changes in BMP2, BMP4 and BMP6 expression during folliculogenesis, in granulosa and theca cells in the COD groups, as well as at different stages of follicular persistence. Results also showed changes in BMPR1B expression in developing follicles in animals with COD, and at the initial stages of follicular persistence (P5). Comparison between groups showed significant differences, mainly in BMP4 and BMP6 expression, in granulosa and theca cells of different follicular categories. The expression of these BMPs also increased in cystic and persistent follicles, in relation to antral follicles of the control group. BMPR1B showed high expression in cystic follicles. Together, these results may indicate an alteration in BMPs, especially in BMP4 and BMP6, as well as in BMPR1B, which occurs early in folliculogenesis and incipiently during the development of COD, which could be a major cause of recurrence of this disease in cattle.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/early/2016/08/01/REP-15-0315/suppl/DC1., (© 2016 Society for Reproduction and Fertility.)

A growing body of evidence suggests that ovulation shares many of the features of an inflammatory reaction and that cytokines play many diverse and important roles in reproductive biology. The aim of this study was to examine the expression of the pro-inflammatory cytokines interleukin (IL)-1α, IL-6 and tumour necrosis factor (TNF)-α in ovarian cells from cows with cystic ovarian disease (COD) as compared with that in ovarian structures from regularly cycling cows. Expression of genes encoding IL-1α, IL-6 and TNF-α was detected by real-time polymerase chain reaction in follicular cells from ovaries from healthy cows and cows with COD with no significant differences. However, immunohistochemistry showed increased expression of IL-1α, IL-6 and TNF-α in cystic follicles, suggesting that this expression may be related to the persistence of follicular cysts. The effect of COD was evident for IL-1α and TNF-α, and a follicular structure-disease interaction was observed in the expression of all the cytokines evaluated. Thus, altered expression of these proinflammatory cytokines may be related to ovulation failure and development of follicular cysts., (Copyright © 2015 Elsevier Ltd. All rights reserved.)