Aspects of embryo-maternal communication in establishment of pregnancy in cattle

Establishment of pregnancy in mammals requires reciprocal molecular communication between the conceptus and endometrium that modifies the endometrial transcriptome and uterine luminal milieu to support pregnancy. Due to the small size of the early embryo and elongating conceptus relative to the volume of the uterine lumen, collection of endometrium adjacent to the developing conceptus is difficult following conventional uterine flushing methods in cattle. Use of endometrial explants in culture can overcome this challenge and reveal information about the dialogue between the developing embryo and the uterus. The aim of this short review is to summarize some of our recent findings in relation to embryo maternal interaction during bovine pregnancy establishment and to put them in the wider context of fertility in cattle.

Aspects of embryo-maternal communication in establishment of pregnancy in cattle

Establishment of pregnancy in mammals requires reciprocal molecular communication between the conceptus and endometrium that modifies the endometrial transcriptome and uterine luminal milieu to support pregnancy. Due to the small size of the early embryo and elongating conceptus relative to the volume of the uterine lumen, collection of endometrium adjacent to the developing conceptus is difficult following conventional uterine flushing methods in cattle. Use of endometrial explants in culture can overcome this challenge and reveal information about the dialogue between the developing embryo and the uterus. The aim of this short review is to summarize some of our recent findings in relation to embryo maternal interaction during bovine pregnancy establishment and to put them in the wider context of fertility in cattle.(AU)

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.

Cellular events during ovine implantation and impact for gestation

The establishment of pregnancy in sheep includes elongation of the blastocyst into a filamentous conceptus, pregnancy recognition, production of histotroph, attachment of the conceptus to the endometrium for implantation, and development of synepitheliochorial placentation. These processes are complex, and this review describes some of the molecular events that underlie and support successful pregnancy. The free-floating sheep blastocyst elongates into a filamentous conceptus and metabolizes, or is responsive to, molecules supplied by the endometrium as histotroph. Amongst these molecules are SPP1, glucose and fructose, and arginine that stimulate the MTOR nutrient sensing system. The placental trophectoderm of elongating conceptuses initiate pregnancy recognition and implantation. The mononucleate cells of the trophectoderm secrete IFNT, which acts on the endometrial LE to block increases in estrogen receptor α to preclude oxytocin receptor expression, thereby preventing oxytocin from inducing luteolytic pulses of PGF2α. In addition, IFNT increases expression of IFN stimulated genes in the endometrial stroma, including ISG15, a functional ubiquitin homologue. Implantation is the initial step in placentation, and includes sequential pre-contact, apposition, and adhesion phases. Implantation in sheep includes downregulation of Muc1 and interaction of GLYCAM1, galectin 15 (LGALS15) and SPP1 with lectins and integrins (αvβ3). Sheep have synepitheliochorial placentation in which mononucleate trophectoderm cells fuse to form binucleate cells (BNCs). BNCs migrate and fuse with endometrial LE cells to form trinucleate syncytial cells, and these syncytia enlarge through continued BNC fusion to form syncytial plaques that form the interface between endometrial and placental tissues within the placentome. The placentae of sheep organize into placentomal and interplacentomal regions. In placentomes there is extensive interdigitation of endometrial and placental tissues to provide hemotrophic nutrition to the fetus. In interplacentomal regions there is epitheliochorial attachment of endometrial LE to trophectoderm, mediated through focal adhesion assembly, and areolae that take up histotroph secreted by endometrial GE.

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)

Cellular events during ovine implantation and impact for gestation

The establishment of pregnancy in sheep includes elongation of the blastocyst into a filamentous conceptus, pregnancy recognition, production of histotroph, attachment of the conceptus to the endometrium for implantation, and development of synepitheliochorial placentation. These processes are complex, and this review describes some of the molecular events that underlie and support successful pregnancy. The free-floating sheep blastocyst elongates into a filamentous conceptus and metabolizes, or is responsive to, molecules supplied by the endometrium as histotroph. Amongst these molecules are SPP1, glucose and fructose, and arginine that stimulate the MTOR nutrient sensing system. The placental trophectoderm of elongating conceptuses initiate pregnancy recognition and implantation. The mononucleate cells of the trophectoderm secrete IFNT, which acts on the endometrial LE to block increases in estrogen receptor α to preclude oxytocin receptor expression, thereby preventing oxytocin from inducing luteolytic pulses of PGF2α. In addition, IFNT increases expression of IFN stimulated genes in the endometrial stroma, including ISG15, a functional ubiquitin homologue. Implantation is the initial step in placentation, and includes sequential pre-contact, apposition, and adhesion phases. Implantation in sheep includes downregulation of Muc1 and interaction of GLYCAM1, galectin 15 (LGALS15) and SPP1 with lectins and integrins (αvβ3). Sheep have synepitheliochorial placentation in which mononucleate trophectoderm cells fuse to form binucleate cells (BNCs). BNCs migrate and fuse with endometrial LE cells to form trinucleate syncytial cells, and these syncytia enlarge through continued BNC fusion to form syncytial plaques that form the interface between endometrial and placental tissues within the placentome. The placentae of sheep organize into placentomal and interplacentomal regions. In placentomes there is extensive interdigitation of endometrial and placental tissues to provide hemotrophic nutrition to the fetus. In interplacentomal regions there is epitheliochorial attachment of endometrial LE to trophectoderm, mediated through focal adhesion assembly, and areolae that take up histotroph secreted by endometrial GE.(AU)

Programação da receptividade uterina e fertilidade em vacas de corte / Uterine receptivity and fertility programming in beef cows

Em bovinos de corte, ocorre significativa mortalidade embrionária durante as três primeiras semanas degestação. Durante esse período, o desenvolvimento de zigoto a concepto depende exclusivamente das secreçõesovidutais e uterinas. O processo de secreção, bem como a qualidade dessas secreções são programados pelaexposição sequencial do trato reprodutivo ao estradiol (E2) durante o proestro/estro e à progesterona (P4)durante o diestro inicial. Estratégias visando a otimização da qualidade dos ambientes ovidutal e uterino para odesenvolvimento embrionário serão discutidas e incluem o gerenciamento do crescimento do folículo pré-ovulatório, a suplementação de E2 no proestro, a suplementação de P4 no diestro inicial e combinações entreelas. Ao final, discute-se a intrigante possibilidade do embrião bovino programar o funcionamento doendométrio já na primeira semana de gestação.(AU)

In beef cattle, there is significant embryonic mortality during the three initial weeks of pregnancy.During this period, the development from zygote to conceptus depends exclusively on secretions from the oviductand uterus. The process of secretion as well as the quality of such secretions are programmed by the sequentialexposure of the reproductive tract to estradiol (E2), during proestrus and estrus, and to progesterone (P4),during early diestrus. Strategies that aim to optimize the quality of the oviductal and the uterine environmentstowards embryo development are discussed. Strategies include managing growth of the pre-ovulatory follicle,E2 supplementation at proestrus, P4 supplementation during early diestrus and combinations. Last but not least,we discuss the intriguing possibility of bovine embryo programming endometrial function as early as the firstweek of gestation.(AU)

Programação da receptividade uterina e fertilidade em vacas de corte / Uterine receptivity and fertility programming in beef cows

Em bovinos de corte, ocorre significativa mortalidade embrionária durante as três primeiras semanas degestação. Durante esse período, o desenvolvimento de zigoto a concepto depende exclusivamente das secreçõesovidutais e uterinas. O processo de secreção, bem como a qualidade dessas secreções são programados pelaexposição sequencial do trato reprodutivo ao estradiol (E2) durante o proestro/estro e à progesterona (P4)durante o diestro inicial. Estratégias visando a otimização da qualidade dos ambientes ovidutal e uterino para odesenvolvimento embrionário serão discutidas e incluem o gerenciamento do crescimento do folículo pré-ovulatório, a suplementação de E2 no proestro, a suplementação de P4 no diestro inicial e combinações entreelas. Ao final, discute-se a intrigante possibilidade do embrião bovino programar o funcionamento doendométrio já na primeira semana de gestação.

In beef cattle, there is significant embryonic mortality during the three initial weeks of pregnancy.During this period, the development from zygote to conceptus depends exclusively on secretions from the oviductand uterus. The process of secretion as well as the quality of such secretions are programmed by the sequentialexposure of the reproductive tract to estradiol (E2), during proestrus and estrus, and to progesterone (P4),during early diestrus. Strategies that aim to optimize the quality of the oviductal and the uterine environmentstowards embryo development are discussed. Strategies include managing growth of the pre-ovulatory follicle,E2 supplementation at proestrus, P4 supplementation during early diestrus and combinations. Last but not least,we discuss the intriguing possibility of bovine embryo programming endometrial function as early as the firstweek of gestation.

Progesterone and conceptus-derived factors important for conceptus survival and growth

Progesterone (P4) from the corpus luteum (CL) is critical for the establishment and maintenance of pregnancy and plays a major role in regulating endometrial secretions essential for stimulating and mediating changes in conceptus growth and differentiation throughout early pregnancy in ruminants. Numerous studies have demonstrated an association between elevated P4 and acceleration in conceptus elongation. A combination of in vivo and in vitro experiments found that the effects of P4 on conceptus elongation are indirect and mediated through P4- induced effects in the endometrium. Despite effects on elongation, data on the impact of post-insemination supplementation of P4 on pregnancy rates are conflicting and typically only result in a modest improvement, if any, in fertility. Differences in conceptus length on the same day of gestation would suggest that factors intrinsic to the blastocysts transferred regulate development, at least in part, and would be consistent with the hypothesis that the quality of the oocyte regulates developmental competence. This paper will review recent knowledge on the effect of P4 on conceptus development in cattle and summarize strategies that have been undertaken to manipulate post fertilization P4 concentrations to increase fertility.

Progesterone and conceptus-derived factors important for conceptus survival and growth

Progesterone (P4) from the corpus luteum (CL) is critical for the establishment and maintenance of pregnancy and plays a major role in regulating endometrial secretions essential for stimulating and mediating changes in conceptus growth and differentiation throughout early pregnancy in ruminants. Numerous studies have demonstrated an association between elevated P4 and acceleration in conceptus elongation. A combination of in vivo and in vitro experiments found that the effects of P4 on conceptus elongation are indirect and mediated through P4- induced effects in the endometrium. Despite effects on elongation, data on the impact of post-insemination supplementation of P4 on pregnancy rates are conflicting and typically only result in a modest improvement, if any, in fertility. Differences in conceptus length on the same day of gestation would suggest that factors intrinsic to the blastocysts transferred regulate development, at least in part, and would be consistent with the hypothesis that the quality of the oocyte regulates developmental competence. This paper will review recent knowledge on the effect of P4 on conceptus development in cattle and summarize strategies that have been undertaken to manipulate post fertilization P4 concentrations to increase fertility.(AU)

Maternal immune responses to conceptus signals during early pregnancy in ruminants

Pregnancy is an immunological paradox created by the hospitable interaction between the maternal immune system and the allogeneic concept us in the gravid uterus. The mother is not immune - suppressed during early pregnancy, nor is the conceptus immune-privileged, shielding itself from maternal immune detection by an immunologically inert placenta. Rather, what is becoming clear is that the conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functioning placenta. In this regard, conceptual thinking derived from immune cell–pathogen interactions inadequately describe the unique homeorhetic mechanisms mediating early conceptus-maternal interactions. Nonetheless, evidence is mounting that conceptus signals induce a tolerogenic (Th2) bias in immune cell function at the fetal-maternal interface. This is accompanied by tissue remodeling and angiogenesis facilitated by tissue-resident immune cells that sets the trajectory for placental growth and, ultimately, fetal growth. Perturbations in these interactions, including systemic inflammation and various stressors at the earliest stages of pregnancy can interfere with communication between the conceptus and uterus , reducing conception rates and resulting in poor pregnancy outcomes.

Maternal immune responses to conceptus signals during early pregnancy in ruminants

Pregnancy is an immunological paradox created by the hospitable interaction between the maternal immune system and the allogeneic concept us in the gravid uterus. The mother is not immune - suppressed during early pregnancy, nor is the conceptus immune-privileged, shielding itself from maternal immune detection by an immunologically inert placenta. Rather, what is becoming clear is that the conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functioning placenta. In this regard, conceptual thinking derived from immune cell–pathogen interactions inadequately describe the unique homeorhetic mechanisms mediating early conceptus-maternal interactions. Nonetheless, evidence is mounting that conceptus signals induce a tolerogenic (Th2) bias in immune cell function at the fetal-maternal interface. This is accompanied by tissue remodeling and angiogenesis facilitated by tissue-resident immune cells that sets the trajectory for placental growth and, ultimately, fetal growth. Perturbations in these interactions, including systemic inflammation and various stressors at the earliest stages of pregnancy can interfere with communication between the conceptus and uterus , reducing conception rates and resulting in poor pregnancy outcomes. (AU)

Mechanisms involved in maintaining the corpus luteum during the first two months of pregnancy

A progesterona (P4) produzida pelo corpo lúteo (CL) é essencial para a manutenção da gestação. Por sua vez, o interferon tau (IFNT) produzido pelo embrião durante o processo de alongamento, além de ser o sinal primário para reconhecimento e manutenção da gestação também é responsável pela manutenção do CL durante a gestação inicial. A presença de receptores de ocitocina (OXTR) no endométrio no momento esperado da luteólise é determinante para liberação uterina de prostaglandina F2 (PGF), a qual é responsável pela regressão do CL. O IFNT evita a ocorrência da luteólise por meio da supressão da expressão de OXTR no endométrio. Entretanto, durante o segundo mês de gestação, CLs acessórios, principalmente contralaterais são capazes de regredir, indicando que ocorre liberação de PGF pelo útero conforme a gestação avança, e os mecanismos que iniciam a luteólise são restabelecidos. Portanto, falhas na manutenção do CL podem causar luteólise e perdas gestacionais de 30 para 60 dias, um dos importantes problemas de eficiência reprodutiva em bovinos, principalmente quando embriões produzidos in vitro (PIV) são transferidos. Dois estudos foram delineados para estudar estes fatores, com foco em determinar o momento em que o útero gravídico retoma a liberação de PGF, e identificar prováveis diferenças entre estes mecanismos em gestações de embriões PIV ou de inseminação artificial (IA). O primeiro estudo avaliou a concentração circulante do metabólito de PGF (PGFM) após desafio com ocitocina durante os primeiros dois meses de gestação em vacas Holandesas lactantes. O tratamento com ocitocina não afetou a concentração de PGFM em vacas de d11 prenhes (P) e não-prenhes (NP), no d18 apresentou um ligeiro aumento em vacas P, enquanto aumentou cerca de duas vezes em relação ao nível basal em vacas NP. O aumento de PGFM induzido por ocitocina em vacas P no dia 25 foi maior que P em d18, entretanto foi menor que vacas P nos dias 53 e 60. Os dias 32, 39 e 46 da gestação tiveram resposta intermediária. O segundo estudo avaliou a PGFM circulante em resposta a ocitocina em vacas Nelore prenhes de embriões PIV ou IA, nos dias 17 e 31 de gestação, e sua associação com fatores que podem impactar no sucesso da prenhes, como P4 circulante, tamanho de concepto no d18, e o tamanho de embrião no d32. Além disso, foi avaliada e localizada a expressão de OXTR e do gene estimulado por interferon 15 (ISG15) no endométrio uterino. O tamanho de embrião no dia 32 e a P4 circulante no dia 31 foram maiores no grupo IA. Vacas do grupo PIV d17 apresentaram menor resposta a ocitocina na concentração de PGFM do que as de IA no mesmo dia, contudo no dia 31 ambos os grupos tiveram maior resposta do que PIV d17. As vacas do d31 dos dois grupos tiveram aumento na PGFM similar às vacas não-inseminadas (NI). Os OXTR foram altamente suprimidosnas vacas prenhes do d18, especialmente no grupo PIV, mas com alta expressão em vacas NI e no dia 32 para os dois grupos, sendo a IA com maior expressão que a PIV neste dia. O gene ISG15 apresentou expressão irrelevante em NI e d32 para IA e PIV, mas apresentou expressão extremamente alta no d18 nos dois grupos prenhes. Conclui- se que o CL na gestação inicial é mantido pela supressão da liberação de PGF, enquanto que no segundo mês, ocitocina induz liberação de PGF, sugerindo que outros mecanismos regem a manutenção do CL a partir do dia 25. Além disso, nossos resultados demonstram que há diferenças entre a sinalização de gestações provenientes de embriões PIV e IA, que impactam no ambiente molecular e endócrino, influenciando a liberação de PGF nestes momentos.

The progesterone (P4) produced by the corpus luteum (CL) is essential for maintenance of pregnancy. On the other hand, the interferon tau (IFNT) produced by the embryo during elongation process, besides being the primary signal for recognition, also is responsible for maintenance of the CL during early pregnancy. The presence of oxytocin receptors (OXTR) in endometrium during expected time of luteolysis is determinant for trigger the uterine release of prostaglandin F2 (PGF), which is in charge of CL regression. The IFNT avoid the luteolysis by suppressing the OXTR appearance. However, during second month, accessory CLs are able to regress, indicating that the PGF release occurs with the advancing of the pregnancy and the mechanisms that initiated luteolysis are recovered. Therefore, failures in maintenance of the CL can cause luteolysis and pregnancy loss during this period of 30 to 60 days, which is one of the most important problems in reproductive efficiency in cattle, specially when in vitro produced (IVP) embryos are transferred. Two experiments were designed to study this factors, focused on point when uterus recover its PGF release during pregnancy and to identify possible differences between those mechanisms on pregnancies from IVP or artificial insemination (AI) embryos. The first study evaluated circulating PGF metabolite (PGFM) after an oxytocin challenge throughout first two months of pregnancy in lactating Holstein cows. Treatment with oxytocin did not affected PGFM concentration in d11 pregnant (P) and non-pregnant (NP), on d18 had a little increase in P cows, while increased 2-fold in NP cows. Oxytocin-induced PGFM in P cows on day 25 was greater than d18 P, however was lower than P cows on d53 and d60. Days 32, 39 and 46 of pregnancy had intermediate response. The second study evaluated the oxytocin-induced PGFM in Nelore cows pregnant from AI or IVP embryos on days 17 and 31, and its association with factors that can impact in success of the pregnancy, such as P4 levels, conceptus length on d18 and size of the embryo on d32. Also, OXTR and interferon-stimulated gene 15 (ISG15) gene expression were evaluated and located in uterine endometrium. Embryo size on d32 and P4 on d31, were higher in AI than IVP. Cows from IVP on d17 presented lower oxytocin-induced PGFM than AI in the same day, however, d31 for both groups had higher PGF release after oxytocin. On d31 there was similar PGFM increase in synchronized non-inseminated group (NI). The OXTR are highly suppressed on pregnant cows on d18, especially in IVP group, but were high expressed in NI cows and on d32 for both groups, AI being higher than IVP at this day. The ISG15 had irrelevant expression on NI and d32 groups, while had extremely high expression in d18 pregnant cows for both groups. Concluding, the CL in early pregnancy is maintained by PGF release suppression, while during second month there is oxytocin-induced PGF release, suggesting that other mechanisms are responsible for maintaining CL after d25. In addition, these results demonstrate there are signaling differences between IVP and AI pregnancies, impacting the molecular and endocrine environment that influences PGF release during these time points.

Biological roles of progesterone, prostaglandins, and interferon tau in endometrial function and conceptus elongation in ruminants

A large majority of pregnancy loss in cattle occus during the firt three weeks afeer conception particularly during the pperi-implantation period. This review integrantes established and new information on the biological role of ovarian progesterone (P4), prostaglandina (PGs) and interferon tau (IFNT) in endometrial function and conceptus elongation during the peri-implantation period of pregnancy in ruminants. Progesterone is secreted by the ovarian corpus luteum (CL) and is the u nequivocal hormone of pregnancy. Prostaglandins are produced from both the endometrium as well as conceptus trophectoderm during early pregnancy. Interferon tau is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signal that inhibits production of luteolytic pulses of PG F2α by the endometrium to maintain the CL and thus production of P4. Conceptus endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in endometrial gene expression during pregnancy. Available results support the idea that the individual, interactive, and coordinated actions of P4, PGs, and IFNT regulate uterine receptivity to conceptus implantation by controlling expression of genes in t he endometrium and that their actions are essential for conceptus elongation. One outcome of gene expression changes in the endometrial epithelia is alterations in lumenal secretions that govern conceptus elongation via effects on the trophectoderm. An increased knowledge of conceptus endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent pregnancy loss and to provide a basis for new strategies to improve fertility, pregnancy outcomes and thus reproductive efficiency.

Biological roles of progesterone, prostaglandins, and interferon tau in endometrial function and conceptus elongation in ruminants

A large majority of pregnancy loss in cattle occus during the firt three weeks afeer conception particularly during the pperi-implantation period. This review integrantes established and new information on the biological role of ovarian progesterone (P4), prostaglandina (PGs) and interferon tau (IFNT) in endometrial function and conceptus elongation during the peri-implantation period of pregnancy in ruminants. Progesterone is secreted by the ovarian corpus luteum (CL) and is the u nequivocal hormone of pregnancy. Prostaglandins are produced from both the endometrium as well as conceptus trophectoderm during early pregnancy. Interferon tau is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signal that inhibits production of luteolytic pulses of PG F2α by the endometrium to maintain the CL and thus production of P4. Conceptus endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in endometrial gene expression during pregnancy. Available results support the idea that the individual, interactive, and coordinated actions of P4, PGs, and IFNT regulate uterine receptivity to conceptus implantation by controlling expression of genes in t he endometrium and that their actions are essential for conceptus elongation. One outcome of gene expression changes in the endometrial epithelia is alterations in lumenal secretions that govern conceptus elongation via effects on the trophectoderm. An increased knowledge of conceptus endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent pregnancy loss and to provide a basis for new strategies to improve fertility, pregnancy outcomes and thus reproductive efficiency.(AU)

Role of diestrus progesterone on endometrial function and conceptus development in cattle

Successful growth and development of the post-hatching blastocyst and pregnancy establishment are a result of the interaction between a competent embryo and a receptive uterine environment. Progesterone (P4) plays a key role in reproductive events associated with establishment and maintenance of pregnancy through its action on the uterine endometrium. Elevated concentrations of circulating P4 in the immediate post conception period have been associated with an ement of conceptus elongation, an increase in interferontau production and higher pregnancy rates in cattle. The potential beneficial effects of exogenous P4 supplementation on fertility have been acknowledged for a long time but results of supplementation have been inconsistent and may be related to the strategy used to achieve high P4 endogenous concentrations in the animal. This review summarizes recent data highlighting the role of progesterone in regulating uterine function and embryo development in cattle.

Role of diestrus progesterone on endometrial function and conceptus development in cattle

Successful growth and development of the post-hatching blastocyst and pregnancy establishment are a result of the interaction between a competent embryo and a receptive uterine environment. Progesterone (P4) plays a key role in reproductive events associated with establishment and maintenance of pregnancy through its action on the uterine endometrium. Elevated concentrations of circulating P4 in the immediate post conception period have been associated with an ement of conceptus elongation, an increase in interferontau production and higher pregnancy rates in cattle. The potential beneficial effects of exogenous P4 supplementation on fertility have been acknowledged for a long time but results of supplementation have been inconsistent and may be related to the strategy used to achieve high P4 endogenous concentrations in the animal. This review summarizes recent data highlighting the role of progesterone in regulating uterine function and embryo development in cattle.(AU)

Uterine environment and conceptus development in ruminants

Interferon tau (IFNT), the pregnancy recognition signal from trophectoderm cells of ruminant conceptuses abrogates the uterine luteolytic mechanism to ensure maintenance of functional corpora lutea for production of progesterone (P4). IFNT acts in concert with P4 to induce expression of genes for transport and/or secretion of histotroph that includes nutrients such as glucose and arginine that activate the mechanistic target of rapamycin (MTOR) nutrient sensing cell signaling pathway to stimulate proliferation, migration, differentiation and translation of mRNAs essential for growth and development of the conceptus. Arginine, leucine, glutamine and glucose increase in the uterine lumen during the peri-implantation period of pregnancy due to increased expression of their transporters by uterine luminal epithelium (LE) and superficial glandular epithelium (sGE) in response to P4 and IFNT. In day 16 ovine conceptus explant cultures, arginine increases GTP cyclohydrolase 1 mRNA, and IFNT, while arginine and glucose increase ornithine decarboxylase, nitric oxide synthase 2, and GCH1. Arginine can be metabolized to nitric oxide (NO) and polyamines which stimulate proliferation of ovine trophectoderm (oTr) cells. Secreted phosphoprotein 1 (SPP1, also known as osteopontin) in uterine histotroph increases focal adhesion assembly as a prerequisite for adhesion and migration of oTr cells through activation and cross-talk between MTOR, MAPK, and myosin II motor pathways. Glucose, arginine, leucine and glutamine stimulate MTOR signaling, proliferation and mRNA translation by oTr cells. Further, glucose and fructose were equivalent in stimulating proliferation and synthesis of hyaluronic acid via the hexosamine pathway in oTr and pig Tr cells. These mechanisms allow select nutrients and SPP1 to act coordinately to affect synthesis of proteins involved in cell signaling affecting conceptus growth, development, and survival during the peri-implantation period of pregnancy.

Uterine environment and conceptus development in ruminants

Interferon tau (IFNT), the pregnancy recognition signal from trophectoderm cells of ruminant conceptuses abrogates the uterine luteolytic mechanism to ensure maintenance of functional corpora lutea for production of progesterone (P4). IFNT acts in concert with P4 to induce expression of genes for transport and/or secretion of histotroph that includes nutrients such as glucose and arginine that activate the mechanistic target of rapamycin (MTOR) nutrient sensing cell signaling pathway to stimulate proliferation, migration, differentiation and translation of mRNAs essential for growth and development of the conceptus. Arginine, leucine, glutamine and glucose increase in the uterine lumen during the peri-implantation period of pregnancy due to increased expression of their transporters by uterine luminal epithelium (LE) and superficial glandular epithelium (sGE) in response to P4 and IFNT. In day 16 ovine conceptus explant cultures, arginine increases GTP cyclohydrolase 1 mRNA, and IFNT, while arginine and glucose increase ornithine decarboxylase, nitric oxide synthase 2, and GCH1. Arginine can be metabolized to nitric oxide (NO) and polyamines which stimulate proliferation of ovine trophectoderm (oTr) cells. Secreted phosphoprotein 1 (SPP1, also known as osteopontin) in uterine histotroph increases focal adhesion assembly as a prerequisite for adhesion and migration of oTr cells through activation and cross-talk between MTOR, MAPK, and myosin II motor pathways. Glucose, arginine, leucine and glutamine stimulate MTOR signaling, proliferation and mRNA translation by oTr cells. Further, glucose and fructose were equivalent in stimulating proliferation and synthesis of hyaluronic acid via the hexosamine pathway in oTr and pig Tr cells. These mechanisms allow select nutrients and SPP1 to act coordinately to affect synthesis of proteins involved in cell signaling affecting conceptus growth, development, and survival during the peri-implantation period of pregnancy.(AU)

Ultrasound evaluation of pregnancy in owl monkey (Aotus azarai infulatus)

Pregnancy in owl monkeys was monitored using u ltrasonography. The obstetric exams were performed using a 5 - 12 MHz linear probe. The measurements included the mean gestational sac diameter (MGSD) , crown - rump length (CRL), biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC ), head area (HA), abdominal circumference (AC), abdominal area (AA) and femur length (FL). The Pearson’s correlation coefficient showed highly significant positive correlations between most of the fetal growth variables (r > 0.90, P < 0.01). The AC x FL a nd AA x FL correlations did have correlation coefficients < 0.90, although this value was still highly significant (P < 0.01) . These results suggest that all of the fetal growth variables are strongly associated with each other.