The equine endometrium and its multiple connections, interrelationships and clinical effects in aged mares

Mares, which make up 90% of animals requiring reproductive assistance in commercial equine production systems, are subjected to strong breeding and reproductive efficiency pressure throughout their lives, but the effects of aging on overall and reproductive systems in particular; it often means that we are forcing the natural homeostasis mechanisms under pressure over time. The objective of this brief communication is to summarize some concepts related to the role and importance of equine endometrium, particularly in old mares, the most challenged category to achieve productive and efficiency goals established by humans. Endometritis is one of the most frequent and recurrent pathologies in equine gynecology and is responsible for enormous economic losses in the industry. Alterations of the microbiota, molecular signals and uterine endocrine microenvironment can lead to infertility, but degenerative phenomena associated with age and parity can lead to endometriosis altering maternal recognition of pregnancy and pregnancy maintenance. Maintaining horses in an adequate nutrition status and environment is essential to achieve pregnancy but also to obtain healthy offspring.(AU)

Efeitos da melatonina exógena na viabilidade embrionária e no ambiente uterino de ovelhas / Effects of exogenous melatonin on embryo viability and uterine environment of ewes

O objetivo deste artigo é revisar o efeito da melatonina na viabilidade embrionária e ambiente uterino em ovinos, tanto in vivo quanto in vitro, considerando as vias pelas quais esse hormônio pode ter influência no embrião ou o mecanismo de reconhecimento materno e estabelecimento de gravidez em ovelhas.(AU)

The aim of this article is to review the effect of melatonin on embryo viability and uterine environment in sheep, both in vivo and in vitro, considering the pathways by which this hormone could have influences at the embryo or the mechanism of maternal recognition and establishment of pregnancy in sheep.(AU)

Galea spixii embryos have potential to produce steroid hormones

Estrogens and progestogens are hormones produced by maternal organs and it is required for recognition and maintenance of pregnancy. In addition, the embryo may also be a source. For this, the aim was to identify steroidogenic expression on Galea spixii embryos early in the embryonic period. Embryos were collected on Days 10 and 15 of gestation; some were fixed in 4% paraformaldehyde for morphological and immunohistochemical analysis (P450arom), whereas others had RNA extracted to determine presence of CYP19a1 gene. In addition, for immunochemistry, maternal ovaries were collected as positive control tissues. Maternal tissues had positive staining for aromatase, whereas none of the embryos stained for P450 aromatase. Based on qPCR reactions, CYP19a1 gene were expressed in all embryos. Galea spixii embryos expressed steroidogenic genes during the post-implantation period, indicating they have the potential to produce steroid hormones.(AU)

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

Abstract The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.

Evaluation of interferon-stimulated gene 15 (ISG15) expression in blood neutrophils in beef cattle poisoned by Senecio spp

ABSTRACT: This study aimed to assess liver damage and interferon-stimulated gene 15 (ISG15) blood expression as a consequence of embryonic signaling on maternal recognition of pregnancy in beef cattle presenting natural ingestion of Senecio spp. Epidemiological aspects, as the presence of the plant, associated to gamma glutamyl transferase (GGT) activity can be used as Senecio spp. poisoning diagnosis. Maternal recognition of pregnancy period occurs when the embryo secretes interferon tau (IFNT) to signal its presence to the mother and eventually extend corpus luteum (CL) lifespan. In our study, liver damage was determined by concentration serum GGT, cytological and histopathological examinations. Reproductive status was evaluated by concentration of progesterone, CL diameter and ISG15 mRNA expression on Day 19 following fixed-time artificial insemination (FTAI). Cows were categorized into two groups based on concentration of GGT: Group 1 (GGT 30U/L) and 2 (GGT>31U/L). No difference on body condition scores was observed. All the cows presented liver damage based on cytology and histopathological exams. Cows from the Group 1 had higher pregnancy rate, presenting larger CL diameter and greater concentration of progesterone. Interestingly, ISG15 mRNA expression had no difference between Groups 1 and 2, even presenting difference in pregnancy status. These findings suggest embryonic loss beyond Day 19. It suggests late embryonic mortality may be associated to liver insufficiency. In conclusion, liver injury and/or concentration of GGT does not alter ISG15 expression on blood neutrophils, however cows presenting lower concentration of GGT ( 30U/L) had increased pregnancy status. Therefore, the concentration of GGT allow us to screen liver status and foresee a successful pregnancy in beef cattle.

RESUMO: O objetivo deste estudo foi avaliar a lesão hepática e a expressão sanguínea do gene estimulado por interferon 15 (ISG15) durante a sinalização embrionária, no reconhecimento materno da gestação, em bovinos de corte apresentando ingestão natural de Senecio spp. Fatores epidemiológicos, como a presença da planta, associados à atividade da gama glutamil transferase (GGT) podem ser utilizados como diagnóstico da intoxicação por Senecio spp. O reconhecimento materno da gestação ocorre quando o embrião secreta interferon tau (IFNT) para sinalizar sua presença à mãe. Em nosso estudo, a lesão hepática foi determinada pela concentração sérica de GGT, pelos exames citológicos e histopatológicos. O estado reprodutivo foi avaliado pela concentração de progesterona, diâmetro de corpo lúteo (CL) e expressão de mRNA ISG15 no Dia 19 após a inseminação artificial em tempo fixo (IATF). As vacas foram separadas em dois grupos com base na concentração de GGT sanguíneo: Grupo 1 (GGT 30U/L) e Grupo 2 (GGT>31U/L). Não foi observada nenhuma diferença no escore de condição corporal entre os grupos. Na citologia e nos exames histopatológicos todas as vacas apresentaram lesão hepática. As vacas do Grupo 1 apresentaram maior taxa de prenhez, maior diâmetro do CL e maior concentração de progesterona. Diferente do esperado, a expressão do mRNA ISG15 não foi diferente entre os Grupos 1 e 2, mesmo apresentando diferença na taxa de prenhez. Esses achados sugerem perda embrionária após o Ddia 19. Isso demonstra que a mortalidade embrionária tardia pode estar associada à insuficiência hepática. Dessa forma, conclui-se que a lesão hepática e/ou concentração de GGT não altera a expressão de ISG15 nos neutrófilos sanguíneos, porém vacas com menor concentração de GGT ( 30U/L) apresentaram maiores taxas de prenhez. Assim, a concentração de GGT nos permite avaliar a saúde hepática e prever uma gestação bem-sucedida em bovinos de corte.

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.(AU)

Evaluation of interferon-stimulated gene 15 (ISG15) expression in blood neutrophils in beef cattle poisoned by Senecio spp / Avaliação da expressão do gene estimulado por interferon 15 (ISG15) em neutrófilos sanguíneos em bovinos de corte intoxicados por Senecio spp

This study aimed to assess liver damage and interferon-stimulated gene 15 (ISG15) blood expression as a consequence of embryonic signaling on maternal recognition of pregnancy in beef cattle presenting natural ingestion of Senecio spp. Epidemiological aspects, as the presence of the plant, associated to gamma glutamyl transferase (GGT) activity can be used as Senecio spp. poisoning diagnosis. Maternal recognition of pregnancy period occurs when the embryo secretes interferon tau (IFNT) to signal its presence to the mother and eventually extend corpus luteum (CL) lifespan. In our study, liver damage was determined by concentration serum GGT, cytological and histopathological examinations. Reproductive status was evaluated by concentration of progesterone, CL diameter and ISG15 mRNA expression on Day 19 following fixed-time artificial insemination (FTAI). Cows were categorized into two groups based on concentration of GGT: Group 1 (GGT<30U/L) and 2 (GGT>31U/L). No difference on body condition scores was observed. All the cows presented liver damage based on cytology and histopathological exams. Cows from the Group 1 had higher pregnancy rate, presenting larger CL diameter and greater concentration of progesterone. Interestingly, ISG15 mRNA expression had no difference between Groups 1 and 2, even presenting difference in pregnancy status. These findings suggest embryonic loss beyond Day 19. It suggests late embryonic mortality may be associated to liver insufficiency. In conclusion, liver injury and/or concentration of GGT does not alter ISG15 expression on blood neutrophils, however cows presenting lower concentration of GGT (<30U/L) had increased pregnancy status. Therefore, the concentration of GGT allow us to screen liver status and foresee a successful pregnancy in beef cattle.(AU)

O objetivo deste estudo foi avaliar a lesão hepática e a expressão sanguínea do gene estimulado por interferon 15 (ISG15) durante a sinalização embrionária, no reconhecimento materno da gestação, em bovinos de corte apresentando ingestão natural de Senecio spp. Fatores epidemiológicos, como a presença da planta, associados à atividade da gama glutamil transferase (GGT) podem ser utilizados como diagnóstico da intoxicação por Senecio spp. O reconhecimento materno da gestação ocorre quando o embrião secreta interferon tau (IFNT) para sinalizar sua presença à mãe. Em nosso estudo, a lesão hepática foi determinada pela concentração sérica de GGT, pelos exames citológicos e histopatológicos. O estado reprodutivo foi avaliado pela concentração de progesterona, diâmetro de corpo lúteo (CL) e expressão de mRNA ISG15 no Dia 19 após a inseminação artificial em tempo fixo (IATF). As vacas foram separadas em dois grupos com base na concentração de GGT sanguíneo: Grupo 1 (GGT<30U/L) e Grupo 2 (GGT>31U/L). Não foi observada nenhuma diferença no escore de condição corporal entre os grupos. Na citologia e nos exames histopatológicos todas as vacas apresentaram lesão hepática. As vacas do Grupo 1 apresentaram maior taxa de prenhez, maior diâmetro do CL e maior concentração de progesterona. Diferente do esperado, a expressão do mRNA ISG15 não foi diferente entre os Grupos 1 e 2, mesmo apresentando diferença na taxa de prenhez. Esses achados sugerem perda embrionária após o Ddia 19. Isso demonstra que a mortalidade embrionária tardia pode estar associada à insuficiência hepática. Dessa forma, conclui-se que a lesão hepática e/ou concentração de GGT não altera a expressão de ISG15 nos neutrófilos sanguíneos, porém vacas com menor concentração de GGT (<30U/L) apresentaram maiores taxas de prenhez. Assim, a concentração de GGT nos permite avaliar a saúde hepática e prever uma gestação bem-sucedida em bovinos de corte.(AU)

Evaluation of interferon-stimulated gene 15 (ISG15) expression in blood neutrophils in beef cattle poisoned by Senecio spp / Avaliação da expressão do gene estimulado por interferon 15 (ISG15) em neutrófilos sanguíneos em bovinos de corte intoxicados por Senecio spp

This study aimed to assess liver damage and interferon-stimulated gene 15 (ISG15) blood expression as a consequence of embryonic signaling on maternal recognition of pregnancy in beef cattle presenting natural ingestion of Senecio spp. Epidemiological aspects, as the presence of the plant, associated to gamma glutamyl transferase (GGT) activity can be used as Senecio spp. poisoning diagnosis. Maternal recognition of pregnancy period occurs when the embryo secretes interferon tau (IFNT) to signal its presence to the mother and eventually extend corpus luteum (CL) lifespan. In our study, liver damage was determined by concentration serum GGT, cytological and histopathological examinations. Reproductive status was evaluated by concentration of progesterone, CL diameter and ISG15 mRNA expression on Day 19 following fixed-time artificial insemination (FTAI). Cows were categorized into two groups based on concentration of GGT: Group 1 (GGT<30U/L) and 2 (GGT>31U/L). No difference on body condition scores was observed. All the cows presented liver damage based on cytology and histopathological exams. Cows from the Group 1 had higher pregnancy rate, presenting larger CL diameter and greater concentration of progesterone. Interestingly, ISG15 mRNA expression had no difference between Groups 1 and 2, even presenting difference in pregnancy status. These findings suggest embryonic loss beyond Day 19. It suggests late embryonic mortality may be associated to liver insufficiency. In conclusion, liver injury and/or concentration of GGT does not alter ISG15 expression on blood neutrophils, however cows presenting lower concentration of GGT (<30U/L) had increased pregnancy status. Therefore, the concentration of GGT allow us to screen liver status and foresee a successful pregnancy in beef cattle.(AU)

O objetivo deste estudo foi avaliar a lesão hepática e a expressão sanguínea do gene estimulado por interferon 15 (ISG15) durante a sinalização embrionária, no reconhecimento materno da gestação, em bovinos de corte apresentando ingestão natural de Senecio spp. Fatores epidemiológicos, como a presença da planta, associados à atividade da gama glutamil transferase (GGT) podem ser utilizados como diagnóstico da intoxicação por Senecio spp. O reconhecimento materno da gestação ocorre quando o embrião secreta interferon tau (IFNT) para sinalizar sua presença à mãe. Em nosso estudo, a lesão hepática foi determinada pela concentração sérica de GGT, pelos exames citológicos e histopatológicos. O estado reprodutivo foi avaliado pela concentração de progesterona, diâmetro de corpo lúteo (CL) e expressão de mRNA ISG15 no Dia 19 após a inseminação artificial em tempo fixo (IATF). As vacas foram separadas em dois grupos com base na concentração de GGT sanguíneo: Grupo 1 (GGT<30U/L) e Grupo 2 (GGT>31U/L). Não foi observada nenhuma diferença no escore de condição corporal entre os grupos. Na citologia e nos exames histopatológicos todas as vacas apresentaram lesão hepática. As vacas do Grupo 1 apresentaram maior taxa de prenhez, maior diâmetro do CL e maior concentração de progesterona. Diferente do esperado, a expressão do mRNA ISG15 não foi diferente entre os Grupos 1 e 2, mesmo apresentando diferença na taxa de prenhez. Esses achados sugerem perda embrionária após o Ddia 19. Isso demonstra que a mortalidade embrionária tardia pode estar associada à insuficiência hepática. Dessa forma, conclui-se que a lesão hepática e/ou concentração de GGT não altera a expressão de ISG15 nos neutrófilos sanguíneos, porém vacas com menor concentração de GGT (<30U/L) apresentaram maiores taxas de prenhez. Assim, a concentração de GGT nos permite avaliar a saúde hepática e prever uma gestação bem-sucedida em bovinos de corte.(AU)

Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy

As the main signal for the maternal recognition in ruminants, interferon-tau (IFNT) stimulates expression of interferon-stimulated genes (ISGs) in uterus and many extrauterine tissues. However, it is unclear that early pregnancy induces expression of signal transducer and activator of transcription 1 (STAT1), myxovirusresistance 1 (Mx1), interferon-gamma-inducible protein 10 (IP-10) and ubiquitin activating enzyme E1-like protein (UBE1L) in maternal thymus. In this study, ovine thymuses were sampled on day 16 of the estrous cycle and on days 13, 16 and 25 of gestation, and the expression of STAT1, Mx1, IP-10 and UBE1L was detected by real-time quantitative PCR, Western blot and immunohistochemistry. The results revealed that the expression of STAT1 and IP-10 reached peaks on day 16 of pregnancy, and expression of Mx1 was enhanced on day 25 of pregnancy, and STAT1 protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. However, expression of UBE1L was declined during early pregnancy. In conclusion, early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep.

Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy

As the main signal for the maternal recognition in ruminants, interferon-tau (IFNT) stimulates expression of interferon-stimulated genes (ISGs) in uterus and many extrauterine tissues. However, it is unclear that early pregnancy induces expression of signal transducer and activator of transcription 1 (STAT1), myxovirusresistance 1 (Mx1), interferon-gamma-inducible protein 10 (IP-10) and ubiquitin activating enzyme E1-like protein (UBE1L) in maternal thymus. In this study, ovine thymuses were sampled on day 16 of the estrous cycle and on days 13, 16 and 25 of gestation, and the expression of STAT1, Mx1, IP-10 and UBE1L was detected by real-time quantitative PCR, Western blot and immunohistochemistry. The results revealed that the expression of STAT1 and IP-10 reached peaks on day 16 of pregnancy, and expression of Mx1 was enhanced on day 25 of pregnancy, and STAT1 protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. However, expression of UBE1L was declined during early pregnancy. In conclusion, early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep.(AU)

Uterine infusion of conceptus fragments changes the protein profile from cyclic mares

This experiment aimed to compare at day seven after ovulation, the protein profile of uterine fluid in cyclic mares with mares infused two days before with Day 13 conceptus fragments. Experimental animals were ten healthy cyclic mares, examined daily to detect ovulation (Day 0) as soon as estrus was confirmed. On day seven, after ovulation, uterine fluid was collected, constituting the Cyclic group (n = 10). The same mares were examined in the second cycle until ovulation was detected. On day five, after ovulation, fragments from a previously collected concepti were infused into each mare's uterus. Two days after infusion, uterine fluid was collected, constituting the Fragment group (n = 10). Two-dimensional electrophoresis technique processed uterine fluid samples. A total of 373 spots were detected. MALDI-TOF/TOF and NanoUHPLC-QTOF mass spectrometry identified twenty spots with differences in abundance between the Cyclic and Fragment group. Thirteen proteins were identified, with different abundance between groups. Identified proteins may be related to embryo-maternal communication, which involves adhesion, nutrition, endothelial cell proliferation, transport, and immunological tolerance. In conclusion, conceptus fragments signalized changes in the protein profile of uterine fluid seven days after ovulation in comparison to the observed at Day 7 in the same cyclic mares.

Uterine infusion of conceptus fragments changes the protein profile from cyclic mares

This experiment aimed to compare at day seven after ovulation, the protein profile of uterine fluid in cyclic mares with mares infused two days before with Day 13 conceptus fragments. Experimental animals were ten healthy cyclic mares, examined daily to detect ovulation (Day 0) as soon as estrus was confirmed. On day seven, after ovulation, uterine fluid was collected, constituting the Cyclic group (n = 10). The same mares were examined in the second cycle until ovulation was detected. On day five, after ovulation, fragments from a previously collected concepti were infused into each mare's uterus. Two days after infusion, uterine fluid was collected, constituting the Fragment group (n = 10). Two-dimensional electrophoresis technique processed uterine fluid samples. A total of 373 spots were detected. MALDI-TOF/TOF and NanoUHPLC-QTOF mass spectrometry identified twenty spots with differences in abundance between the Cyclic and Fragment group. Thirteen proteins were identified, with different abundance between groups. Identified proteins may be related to embryo-maternal communication, which involves adhesion, nutrition, endothelial cell proliferation, transport, and immunological tolerance. In conclusion, conceptus fragments signalized changes in the protein profile of uterine fluid seven days after ovulation in comparison to the observed at Day 7 in the same cyclic mares.(AU)

Actions of interferon tau during maternal recognition of pregnancy / Ações do interferon tau durante o reconhecimento materno da gestação

Maternal recognition of pregnancy in ruminants is a physiological process that requires an interaction between the conceptus and the mother in order to avoid luteal regression. Studies on 60s started to investigate the communication, and late on the 80s it was identified a Type I interferon called interferon tau. In the 90s the local action of interferon tau was described. It suppresses luteolytic pulses of prostaglandin F2 alpha inhibiting endometrial expression of estrogen and oxytocin receptors. Several studies presented the expression of interferonstimulated genes on extrauterine tissues. After, the endocrine action of interferon tau was described. This study revealed a greater interferon bioactivity in the serum of uterine vein from pregnant ewes when compared to nonpregnant ewes. Following a series of experiments were preformed to better understand the endocrine action of interferon tau in several extrauteine tissues. This review presents the endocrine action of interferon tau during maternal recognition of pregnancy period in ruminants.(AU)

O reconhecimento materno da gestação em ruminantes é um processo fisiológico que requer a interação entre o concepto e a mãe com o obejetivo de evitar a regressão luteal. Estudos na década de 1960 começaram a investigar essa comunicação entre concepto e mãe, e durante a década de 1980 foi identificado um tipo I de interferon que foi denominado interferon tau. Nos anos 1990, foi descrita a ação local do interferon tau. Essa ação suprime os pulsos luteolíticos de prostaglandina F2 alfa inibindo a expressão endometrial dos receptors de estrógeno e ocitocina. Muitos estudos têm apresentado a expressão dos genes estimulados por interferons nos tecidos extrauterinos. Posteriormente, a ação endócrina do interferon tau também foi descrita. Este estudo revelou uma maior bioatividade de interferon no soro da veia uterina de ovelhas prenhes quando comparada com ovelhas não gestantes. Após, uma série de experimentos foram realizados para melhor compreender a ação endócrina do interferon tau em vários tecidos extrauterinos. Esta revisão destaca a ação endócrina do interferon tau durante o período de reconhecimento materno da gestação em ruminantes.(AU)

Actions of interferon tau during maternal recognition of pregnancy / Ações do interferon tau durante o reconhecimento materno da gestação

Maternal recognition of pregnancy in ruminants is a physiological process that requires an interaction between the conceptus and the mother in order to avoid luteal regression. Studies on 60’s started to investigate the communication, and late on the 80’s it was identified a Type I interferon called interferon tau. In the 90’s the local action of interferon tau was described. It suppresses luteolytic pulses of prostaglandin F2 alpha inhibiting endometrial expression of estrogen and oxytocin receptors. Several studies presented the expression of interferonstimulated genes on extrauterine tissues. After, the endocrine action of interferon tau was described. This study revealed a greater interferon bioactivity in the serum of uterine vein from pregnant ewes when compared to nonpregnant ewes. Following a series of experiments were preformed to better understand the endocrine action of interferon tau in several extrauteine tissues. This review presents the endocrine action of interferon tau during maternal recognition of pregnancy period in ruminants.

O reconhecimento materno da gestação em ruminantes é um processo fisiológico que requer a interação entre o concepto e a mãe com o obejetivo de evitar a regressão luteal. Estudos na década de 1960 começaram a investigar essa comunicação entre concepto e mãe, e durante a década de 1980 foi identificado um tipo I de interferon que foi denominado interferon tau. Nos anos 1990, foi descrita a ação local do interferon tau. Essa ação suprime os pulsos luteolíticos de prostaglandina F2 alfa inibindo a expressão endometrial dos receptors de estrógeno e ocitocina. Muitos estudos têm apresentado a expressão dos genes estimulados por interferons nos tecidos extrauterinos. Posteriormente, a ação endócrina do interferon tau também foi descrita. Este estudo revelou uma maior bioatividade de interferon no soro da veia uterina de ovelhas prenhes quando comparada com ovelhas não gestantes. Após, uma série de experimentos foram realizados para melhor compreender a ação endócrina do interferon tau em vários tecidos extrauterinos. Esta revisão destaca a ação endócrina do interferon tau durante o período de reconhecimento materno da gestação em ruminantes.

Physiological and cellular requirements for successful elongation of the preimplantationconceptus and the implications for fertility in lactating dairy cows

Elongation of the preimplantation conceptus is a prerequisite for maternal recognition of pregnancy and implantation in ruminants. Failures in this phase of development likely contribute for the subfertility of lactating dairy cows. This review will discuss our current understanding of the physiological and cellular requirements for successful elongation of the preimplantation conceptus and their potential deficiency in subfertile lactating dairy cows. Major requirements include the priming of the endometrium by ovarian steroids, reprogramming of trophectoderm cells at the onset of elongation, and intensification of the crosstalk between elongating conceptus and endometrium. Conceptus elongation and survival in dairy cows does not seem to be affected by lactation per se but seem to be altered in subgroups of cows with endocrine, metabolic and nutritional imbalances or deficiencies. These subgroups of cows include those suffering diseases postpartum, anovular cows enrolled in synchronization programs, and cows with low concentration of circulating steroids and IGF1. Success of conceptus elongation starts long before breeding and entails optimization of health and nutrition programs, especially during the transition period, and might be extended to the supplementation of endocrine and nutritional shortages at the time of breeding. Genetic selection will eventually become more important as researchers unravel the molecular control of reproduction and develop new fertility traits focused on pregnancy survival.

Physiological and cellular requirements for successful elongation of the preimplantationconceptus and the implications for fertility in lactating dairy cows

Elongation of the preimplantation conceptus is a prerequisite for maternal recognition of pregnancy and implantation in ruminants. Failures in this phase of development likely contribute for the subfertility of lactating dairy cows. This review will discuss our current understanding of the physiological and cellular requirements for successful elongation of the preimplantation conceptus and their potential deficiency in subfertile lactating dairy cows. Major requirements include the priming of the endometrium by ovarian steroids, reprogramming of trophectoderm cells at the onset of elongation, and intensification of the crosstalk between elongating conceptus and endometrium. Conceptus elongation and survival in dairy cows does not seem to be affected by lactation per se but seem to be altered in subgroups of cows with endocrine, metabolic and nutritional imbalances or deficiencies. These subgroups of cows include those suffering diseases postpartum, anovular cows enrolled in synchronization programs, and cows with low concentration of circulating steroids and IGF1. Success of conceptus elongation starts long before breeding and entails optimization of health and nutrition programs, especially during the transition period, and might be extended to the supplementation of endocrine and nutritional shortages at the time of breeding. Genetic selection will eventually become more important as researchers unravel the molecular control of reproduction and develop new fertility traits focused on pregnancy survival.(AU)

The role of cytokines in immune regulation of female reproductive physiology / O papel das citocinas na imunorregulação da fisiologia reprodutiva da fêmea

Cytokines act as protein mediators of the immune system and exert pleiotropic effects on the source cells and/or on target cells. Cytokines are formed in a cascade, bind to specific receptors, and influence the activity, differentiation, proliferation, and survival of immune cells of both T helper 1 (Th1) type (which has proinflammatory properties) and Th2 type (with an anti-inflammatory function). The female reproductive system is regulated by the immune system via cytokines at various physiological stages: during the ovarian cycle, maternal recognition, embryo implantation, gestation, and birth, participating in homeostasis and protection from pathogens. These processes interact under the hormonal influence of the hypothalamic–pituitary–gonadal axis. This review is aimed at addressing the involvement of some cytokines in female reproductive physiology, highlighting the maternal recognition of the embryo and implantation as immunologically important steps for fetal survival. The scientific knowledge on the role of cytokines in female reproduction processes, such as the Th1/Th2 balance and immune tolerance should advance the research in various fields of assisted reproduction in humans and animals, such as artificial insemination, embryo transfer, and in vitro fertilization. The same is true for the development of contraceptive methods and understanding of pathological processes such as uterine infections and autoimmune diseases.(AU)

Citocinas funcionam como mediadores proteicos do sistema imunológico, que exercem efeitos pleiotrópicos nas próprias células e/ou em células-alvo; formadas em cascata e ligando-se a receptores específicos, influenciam a atividade, diferenciação, proliferação e sobrevida da célula imunológica, tanto tipo Th1 (Thelper1), de ação pró-inflamatória, quanto tipo Th2 (Thelper2), de ação anti-inflamatória. O sistema reprodutivo das fêmeas é imunorregulado pelas citocinas em seus diversos estágios fisiológicos: ciclos ovarianos, reconhecimento materno e implantação do embrião, avanço da gestação e parto, auxiliando na homeostase e prevenção contra patógenos, interagindo sob influência hormonal do eixo hipotalâmico-hipofisário-gonadal. Esta revisão tem como objetivo abordar o envolvimento de algumas citocinas na fisiologia reprodutiva feminina, destacando o reconhecimento materno do embrião e a implantação como etapas imunologicamente importantes à sobrevida fetal. É possível constatar que o conhecimento científico sobre as citocinas na reprodução de fêmeas, como o balanço Th1/Th2 e a imunotolerância, permite um sólido avanço de pesquisas nas áreas de Reprodução Assistida em humanos e animais, a exemplo da inseminação artificial, transferência de embriões e fertilização in vitro, bem como no desenvolvimento de métodos contraceptivos e compreensão de processos patológicos, como infecções uterinas e doenças auto-imunes.(AU)

Pregnancy recognition signals in mammals: the roles of interferons and estrogens

Reproduction is a highly complex biologicalprocess requiring a dialogue between the developingconceptus (embryo-fetus and associated placentalmembranes) and maternal uterus which must beestablished during the peri-implantation period forpregnancy recognition signaling and regulation of geneexpression by uterine epithelial and stromal cells. Theuterus provide a microenvironment in which moleculessecreted by uterine epithelia or transported into theuterine lumen represent histotroph or the secretomerequired for growth and development of the conceptusand receptivity of the uterus to implantation by theconceptus. Pregnancy recognition signaling as related tosustaining the functional lifespan of the corpora lutea(CL) which produce progesterone; the hormone ofpregnancy essential for uterine functions that supportimplantation and placentation required for successfuloutcomes of pregnancy. It is within the periimplantationperiod that most embryonic deaths occur inmammals due to deficiencies attributed to uterinefunctions or failure of the conceptus to developappropriately, signal pregnancy recognition and/orundergo implantation and placentation. The endocrinestatus of the pregnant female and her nutritional status arecritical for successful establishment and maintenance ofpregnancy. The challenge is to understand the complexityof key mechanisms that are characteristic of successfulreproduction and to use that knowledge to enhancefertility and reproductive health of animals includingnonhuman primates. It is important to translateknowledge gained from studies of animals to addressissues of fertility and reproductive health in humans.

Pregnancy recognition signals in mammals: the roles of interferons and estrogens

Reproduction is a highly complex biologicalprocess requiring a dialogue between the developingconceptus (embryo-fetus and associated placentalmembranes) and maternal uterus which must beestablished during the peri-implantation period forpregnancy recognition signaling and regulation of geneexpression by uterine epithelial and stromal cells. Theuterus provide a microenvironment in which moleculessecreted by uterine epithelia or transported into theuterine lumen represent histotroph or the secretomerequired for growth and development of the conceptusand receptivity of the uterus to implantation by theconceptus. Pregnancy recognition signaling as related tosustaining the functional lifespan of the corpora lutea(CL) which produce progesterone; the hormone ofpregnancy essential for uterine functions that supportimplantation and placentation required for successfuloutcomes of pregnancy. It is within the periimplantationperiod that most embryonic deaths occur inmammals due to deficiencies attributed to uterinefunctions or failure of the conceptus to developappropriately, signal pregnancy recognition and/orundergo implantation and placentation. The endocrinestatus of the pregnant female and her nutritional status arecritical for successful establishment and maintenance ofpregnancy. The challenge is to understand the complexityof key mechanisms that are characteristic of successfulreproduction and to use that knowledge to enhancefertility and reproductive health of animals includingnonhuman primates. It is important to translateknowledge gained from studies of animals to addressissues of fertility and reproductive health in humans.(AU)

Regressão espontânea do corpo lúteo em bovinos - revisão / Spontaneous corpus luteum regression in cattle: review

O conhecimento do processo de luteólise dentro da fisiologia reprodutiva se torna importante para que ocorra a compreensão do reconhecimento materno da gestação e seja possível formular estratégias anti-luteolíticas que visem manter esta fase conferindo aumentos na eficiência reprodutiva e produtiva. Durante o processo de luteólise, o tecido luteal sofre mudanças bruscas na capacidade esteroidogênica, vascularização e remodelamento, resultando em substituição da glândula por tecido conjuntivo, sendo a PGF2α o principal determinante na indução espontânea da luteólise em bovinos. Simultaneamente, ocorre um íntimo processo entre as relações anatômicas que compreende o ovário, útero e suas vascularizações. A exposição do útero à interação coordenada entre P4, E2 e ocitocina aliada à expressão de seus receptores são essenciais para a secreção pulsátil de PGF2α pelo endométrio a qual induzirá a luteólise. Nesta regressão do corpo lúteo (CL), estão envolvidos ainda os hormônios (LH, prolactina, cortisol) e várias substâncias vasoativas (óxido nítrico, VEGF, EG-VEGF, bFGF, END-1, AngII). A concentração de PGF2α pode ser representada pela mensuração sanguínea da concentração de seu metabólito 13,14-dihidro-15-ceto- PGF2α (PGFM) sendo a pulsatilidade da secreção de PGF2α durante os períodos pré-luteolítico, luteolítico e pós-luteolítico mensurável pelo aumento na concentração de PGFM. Neste artigo de revisão, será possível compreender e discutir os principais aspectos endócrinos e moleculares que ocorrem com as mudanças morfofuncionais no CL durante o processo de luteólise fisiológica em fêmeas bovinas.

The knowledge of the luteolysis process within reproductive physiology becomes important to occur the understanding of maternal recognition of gestation being possible to formulate anti-luteolytic strategies aimed at maintaining this phase conferring increases in reproductive and productive efficiency. During the luteolysis process, luteal tissue undergoes abrupt changes in steroidogenic capacity, vascularization and remodeling, resulting in replacement of the gland by connective tissue, and PGF2α is the main determinant in the spontaneous induction of luteolysis in cattle. Simultaneously, an intimate process occurs between the anatomical relationships that comprise the ovary, uterus and its vascularizations. The exposure of the uterus to the coordinated interaction between P4, E2 and oxytocin, together with the expression of its receptors, are essential for the pulsating secretion of PGF2α by the endometrium, which will induce luteolysis. In this regression of the corpus luteum (CL), hormones (LH, prolactin, cortisol) and various vasoactive substances (nitric oxide, VEGF, EG-VEGF, bFGF, END-1, AngII) are also involved. The concentration of PGF2α can be represented by the blood measurement of the concentration of its metabolite 13,14-dihydro-15-keto-PGF2α (PGFM),being the pulsatility of PGF2α secretion during the pre-luteolytic, luteolytic and post-luteolytic measured by the increased concentration of PGFM. In this review article, it will be possible to understand and discuss the main endocrine and molecular aspects that occur with the morphofunctional changes in CL during the physiological luteolysis process in bovine females.