O embrião equino apresenta um desenvolvimento dinâmico por um longo período entre a fertilização, sua entrada no útero, fixação e posterior invasão trofoblástica após o 36º dia da gestação. Durante todo este período o concepto é sustentado pelo histotrofo endometrial. Estas características dos equídeos favorecem o seu uso com modelo experimental in vivo para estudos nos desenvolvimentos e interações fetal e maternal. Os estudos em endométrio equino tiveram foco em eventos fisiológicos nas diferentes fases do ciclo estral, enquanto os estudos aos primeiros momentos da gestação são escassos. O entendimento do processo de remodelação e morfofisiologia do endométrio após a entrada do embrião no útero não é completamente entendido. O objetivo deste trabalho foi estudar a morfofisiologia endometrial da gestação na égua envolvendo os períodos pós-fixação e peri-implantação, por histologia e microscopia eletrônica de varredura. A característica mais marcante da transformação ou adaptação endometrial à gestação foi o quase total desaparecimento das células ciliadas na superfície epitelial em ambos cornos uterinos. A capacidade de secreção das células microvilosas também passou por mudanças com o avanço gestacional. Muitas células secretórias ingurgitadas e protusas formam a maioria da população do epitélio, onde o histotrofo se acumula, e apresentaram erosões em sua superfície, provavelmente pela secreção apócrina de vesículas. A superfície epitelial apresentou pleomorfismo celular e pseudoestratificação, promovida por intensa hiperplasia celular, acompanhada de adensamento das glândulas endometriais, desde o 21º dia da gestação diminuído após o 36º dia. Linfócitos, provavelmente uNK, foram encontrados no epitélio luminal do endométrio já aos 21 dias de gestação em ambos cornos, gravídico e não gravídico. Foi evidenciado o septamento no epitélio luminal, com sulcos formados aos 35 e 36 dias, tornando-se mais profundos aos 42 dias de gestação. Toda esta evolução e adaptação contínua aconteceram principalmente no corno gravídico acompanhados em menor intensidade pelo corno não gravídico. / The equine embryo plays a dynamic development for a long period between fertilization, its entry into the uterus, fixes and subsequent trophoblastic invasion after day 36 of gestation. Throughout this period, the conceptus is supported by endometrial histotrophe. These equids characteristics favor their use as an in vivo experimental model for studying the changes and interactions in fetal and maternal development. Studies in equine endometrium were focused on physiological events in the different phases of the estrous cycle, while studies in early moments of pregnancy are scant. The process of endometrial remodeling and morphophysiology after the maternal recognition of pregnancy is not completely understood. The objective of this work was to study the endometrial morphophysiology in the mare comprising post-fixation and peri-implantation periods, by histology and scanning electron microscopy. The most striking feature of endometrial transformation or adaptation to pregnancy was the almost total ciliated cells disappearance of the epithelial surface in both uterine horns. In addition, the secretory capacity of microvillus cells underwent changes with gestational age. Many engorged and protruded secretory cells were the majority epithelium population where histotroph accumulates, and showed erosions on its surface, probably by apocrine vesicle secretion. The epithelial surface also showed cellular pleomorphic and pseudostratified epithelium as a result of intense cell hyperplasia. It was accompanied by thickening of the endometrial glands from day 21 of gestation, then decreasing after the 36th day. Lymphocytes, probably uNK, were found in the luminal epithelium of the endometrium since 21st day of gestation in both pregnant and not pregnant horns. Septation was evidenced in the luminal epithelium, with sulci formed at 35 days, becoming deeper at 42 days of pregnancy. All this continued evolution and adaptation occurred mainly in the gravid horn accompanied in less intensity by non-gravid horn.

O embrião equino apresenta um desenvolvimento dinâmico por um longo período entre a fertilização, sua entrada no útero, fixação e posterior invasão trofoblástica após o 36º dia da gestação. Durante todo este período o concepto é sustentado pelo histotrofo endometrial. Estas características dos equídeos favorecem o seu uso com modelo experimental in vivo para estudos nos desenvolvimentos e interações fetal e maternal. Os estudos em endométrio equino tiveram foco em eventos fisiológicos nas diferentes fases do ciclo estral, enquanto os estudos aos primeiros momentos da gestação são escassos. O entendimento do processo de remodelação e morfofisiologia do endométrio após a entrada do embrião no útero não é completamente entendido. O objetivo deste trabalho foi estudar a morfofisiologia endometrial da gestação na égua envolvendo os períodos pós-fixação e peri-implantação, por histologia e microscopia eletrônica de varredura. A característica mais marcante da transformação ou adaptação endometrial à gestação foi o quase total desaparecimento das células ciliadas na superfície epitelial em ambos cornos uterinos. A capacidade de secreção das células microvilosas também passou por mudanças com o avanço gestacional. Muitas células secretórias ingurgitadas e protusas formam a maioria da população do epitélio, onde o histotrofo se acumula, e apresentaram erosões em sua superfície, provavelmente pela secreção apócrina de vesículas. A superfície epitelial apresentou pleomorfismo celular e pseudoestratificação, promovida por intensa hiperplasia celular, acompanhada de adensamento das glândulas endometriais, desde o 21º dia da gestação diminuído após o 36º dia. Linfócitos, provavelmente uNK, foram encontrados no epitélio luminal do endométrio já aos 21 dias de gestação em ambos cornos, gravídico e não gravídico. Foi evidenciado o septamento no epitélio luminal, com sulcos formados aos 35 e 36 dias, tornando-se mais profundos aos 42 dias de gestação. Toda esta evolução e adaptação contínua aconteceram principalmente no corno gravídico acompanhados em menor intensidade pelo corno não gravídico. / The equine embryo plays a dynamic development for a long period between fertilization, its entry into the uterus, fixes and subsequent trophoblastic invasion after day 36 of gestation. Throughout this period, the conceptus is supported by endometrial histotrophe. These equids characteristics favor their use as an in vivo experimental model for studying the changes and interactions in fetal and maternal development. Studies in equine endometrium were focused on physiological events in the different phases of the estrous cycle, while studies in early moments of pregnancy are scant. The process of endometrial remodeling and morphophysiology after the maternal recognition of pregnancy is not completely understood. The objective of this work was to study the endometrial morphophysiology in the mare comprising post-fixation and peri-implantation periods, by histology and scanning electron microscopy. The most striking feature of endometrial transformation or adaptation to pregnancy was the almost total ciliated cells disappearance of the epithelial surface in both uterine horns. In addition, the secretory capacity of microvillus cells underwent changes with gestational age. Many engorged and protruded secretory cells were the majority epithelium population where histotroph accumulates, and showed erosions on its surface, probably by apocrine vesicle secretion. The epithelial surface also showed cellular pleomorphic and pseudostratified epithelium as a result of intense cell hyperplasia. It was accompanied by thickening of the endometrial glands from day 21 of gestation, then decreasing after the 36th day. Lymphocytes, probably uNK, were found in the luminal epithelium of the endometrium since 21st day of gestation in both pregnant and not pregnant horns. Septation was evidenced in the luminal epithelium, with sulci formed at 35 days, becoming deeper at 42 days of pregnancy. All this continued evolution and adaptation occurred mainly in the gravid horn accompanied in less intensity by non-gravid horn.

Uterine NK (uNK) cells are a distinct subset of NK cells in the decidua of humans and rodents during pregnancy, which are essential for remodelling of the spiral arteries supplying the feto-placental unit. Similarly to peripheral NK cells, uNK cells express Natural Killer receptors (NKRs) that engage MHC class I molecules. Evidence from human genetic association studies suggests that, in the presence of allogeneic cognate paternal MHC class I ligands, inhibitory uterine NKRs are associated with disorders of pregnancy arising from impaired decidual vascular remodelling. Conversely, enhancement of human uNK cell activity through activating NKRs is associated with high birth weight. Evidence from mouse models corroborates that uNK cell activity is modulated by interactions between NKRs and MHC class I, but has largely focussed on the effect of paternal MHC. In this study, the contribution of maternal immunogenetic regulation of NK cell function to reproductive outcome was assessed independently of parental MHC disparity in mice. To evaluate the role of NKR genes in isolation, I used congenic B6.BALB-TC1 (TC1) mice that differ from C57BL/6 (B6) mice only within the region of chromosome six encoding NKRs that recognise MHC class I. Absence of a major inhibitory NKR for self-MHC, Ly49I, in TC1 mice causes a compensatory shift in the NKR repertoire expressed and preserves a majority subpopulation of educated NK cells. B6 and TC1 splenic and uterine NK cells are similarly functionally reactive and mature, and no significant differences could be detected in spiral arterial remodelling or fetal growth between these strains in MHC-syngeneic matings. This supports data from human immunogenetic studies showing that maternal uterine NKRs are not associated with differences in pregnancy outcome in the absence of novel paternal MHC class I ligands, and highlights the importance of maternal and paternal co-regulation of uNK cell activity during pregnancy. No mouse models of uNK cell activation are currently available with which to corroborate human immunogenetic associations between activating uterine NKRs and high birth weight. Male m157-transgenic (m157-Tg) mice, which ubiquitously express viral m157 glycoprotein ligands for the activating NKR Ly49H, were mated with B6 females. Exclusive expression of m157 glycoprotein by trophoblast improved placental efficiency, but did not enhance fetal growth. Some fertility clinics surmise that uNK cell activation initiates the pathogenesis of spontaneous abortion. It has been suggested that this may occur due to reduced expression by human uNK cells of miR-483-3p, which stimulates endogenous insulin-like growth factor (IGF)-1 production and uNK cell cytotoxicity in vitro. It is demonstrated here that neither miR-483-3p nor IGF-1 regulate murine NK cell development, maturation or function. No discernible reproductive phenotype is evident in miR-483 deficient females. It can be inferred that post-transcriptional control by miR-483 is not biologically relevant to murine NK cell function. Although m157-Tg mice may provide an interesting model to further study uNK cell-mediated placental adaptations, it remains important to identify a murine model of enhanced uNK cell function to corroborate human immunogenetic associations with high birth weight and to challenge the supposition that uNK cell activation is harmful to pregnancy.