La neosporosis bovina y la toxoplasmosis ovina son dos enfermedades parasitarias que causan importantes pérdidas económicas en el sector ganadero debido al fallo reproductivo que ocasionan.
Estas enfermedades están causadas por Neospora caninum y Toxoplasma gondii, respectivamente, ambos son parásitos apicomplejos formadores de quistes estrechamente relacionados, y que comparten muchas características morfológicas y biológicas24,25.
La neosporosis bovina tiene una gran importancia en el ganado vacuno, ya que es una de las principales causas de aborto a nivel mundial, originando graves pérdidas económicas. El aborto es el principal signo clínico de la neosporosis bovina.
Los fetos de las madres infectadas por N. caninum pueden morir en el útero y ser reabsorbidos, momificados, sufrir autolisis o nacer muertos.
Las vacas de cualquier edad pueden abortar desde los 3 meses de gestación hasta su término, observándose la mayoría de los abortos a los 5-7 meses de gestación21.
Si la infección ocurre después de la mitad de la gestación pueden nacer terneros vivos con signos clínicos o clínicamente normales, pero persistentemente infectados.
El fallo reproductivo puede producirse también en otros rumiantes como ovejas, cabras y ciervos21,26,27.
 En la actualidad, no existen vacunas ni tratamientos eficaces contra la infección por N. caninum28,29 y las opciones de control se basan en el diagnóstico y en medidas de bioseguridad y manejo21. |
Por otro lado, la toxoplasmosis se considera una de las principales causas de pérdidas reproductivas en ovejas y cabras en todo el mundo22,30.
La infección durante la gestación suele provocar la muerte del feto (infección al principio de la gestación); el nacimiento de corderos muertos o débiles, a veces acompañados de un feto de tamaño más pequeño y momificado (infección a mitad de gestación); o el nacimiento de corderos sanos, pero infectados congénitamente (infecciones durante el último tercio de la gestación)31.
Es responsable del 10-23% de los abortos ovinos en Europa y EE.UU.32 y podría ser responsable de entre 680.000 y 1.360.000 abortos anuales en la UE.
La toxoplasmosis es además una importante zoonosis y los pequeños rumiantes pueden desempeñar un papel importante en su transmisión a los humanos33.
El control de la toxoplasmosis ovina se basa principalmente en la prevención de su transmisión horizontal y en el establecimiento de un programa de vacunación con una cepa viva atenuada S48 (Ovilis Toxovax®).
¿QUÉ TIENEN EN COMÚN N. caninum y T. gondii?
N. caninum y T. gondii comparten muchas características en sus ciclos biológicos, sin embargo, ambos difieren en su rango de hospedadores, el potencial zoonósico (demostrado sólo para T. gondii) y la relevancia de las vías de transmisión horizontal y vertical en el mantenimiento de las infecciones en la naturaleza21,34.
En ambos casos, los hospedadores definitivos son los únicos capaces de producir ooquistes, que son liberados con las heces, mientras que los hospedadores intermediarios desarrollan quistes tisulares repletos de bradizoítos en el tejido muscular y nervioso, donde se cronifica la infección.
 El ciclo biológico de N. caninum implica a l os cánidos como hospedadores definitivos, y a los rumiantes como los principales hospedadores intermediarios. |
N. caninum no se considera zoonósico, ya que no se ha detectado la presencia del parásito en los tejidos humanos35.
La infección postnatal por ingestión de ooquistes (transmisión horizontal) y el paso transplacentario del parásito de la madre al feto (transmisión vertical) son las únicas vías de transmisión demostradas para el ganado y otros hospedadores intermediarios.
A su vez, se han descrito dos formas distintas de transmisión transplacentaria en la neosporosis bovina:
Transmisión transplacentaria endógena: es la más frecuente, y se debe a la reactivación durante la gestación de los bradizoítos presentes en los en las madres persistentemente infectadas.
Transmisión transplacentaria exógena: es menos frecuente, y sucede cuando las madres se infectan por primera vez durante la gestación por ingestión de ooquistes.
La ingestión de bradizoítos contenidos en los quistes tisulares presentes en el hospedador intermediario es la fuente más probable de infección para el hospedador definitivo21.
Por otro lado, los gatos domésticos y otros félidos son los hospedadores definitivos de T. gondii.
La vía más importante de transmisión de T. gondii a los pequeños rumiantes es la horizontal, tras la ingestión oral de ooquistes esporulados que contaminan el forraje o el agua36.
Se estima que sólo el 2% de las ovejas se infectan de forma congénita y que el 4% de las ovejas infectadas de forma persistente transmiten la infección a sus crías37.
También se ha descrito la transmisión transplacentaria endógena del parásito en cabras38.
La interacción de estos parásitos con la placenta es de gran importancia y determina el curso de la infección, pudiendo ocasionar la muerte del feto o la transmisión del parásito a la descendencia. Sin embargo, no se conoce el mecanismo que produce el aborto y todavía hay importantes incógnitas por esclarecer.
| Los modelos animales de rumiantes siguen siendo una herramienta indispensable para proporcionar una visión global de la patogenia de estas enfermedades, pero su utilización conlleva importantes restricciones económicas y éticas. |
A continuación, resumiremos las características anatómicas y funcionales de la placenta de los rumiantes en este primer artículo para, en una segunda parte, describir las alternativas de los modelos posibles, junto con sus ventajas e inconvenientes, para el estudio de estos parásitos en la placenta.
LA PLACENTA DE LOS RUMIANTES 
La placenta desempeña un papel fundamental en la patogenia de estas enfermedades, ya que es una barrera biológica que debe atravesar el parásito para infectar al feto. Además, desde el punto de vista inmunológico, en la placenta se produce una respuesta antiinflamatoria que permite:
- La implantación del embrión y garantizar su supervivencia (tolerancia inmunológica).
- A la vez, podría favorecer la multiplicación del parásito en la placenta y su transmisión al feto, comprometiendo su supervivencia.
Al mismo tiempo, las células de la placenta son capaces de defenderse frente a una infección produciendo una respuesta inflamatoria que podría ser potencialmente dañina para el feto e inducir el aborto1.
A pesar de ello, N. caninum y T. gondii son capaces de replicarse en los tejidos de la placenta, comprometiendo el éxito de la gestación.
En los mamíferos, el crecimiento y la supervivencia del feto dependen de la placenta, un órgano temporal formado por un entramado de tejidos maternos y fetales que mantiene a ambos individuos conectados (Figura 1).
Los rumiantes domésticos presentan placentas corioalantoideas, vellosas y cotiledonarias.
Estos términos se refieren a la fusión del corion y el alantoides en zonas discretas de la placenta fetal para formar proyecciones vellosas denominadas cotiledones.
En los rumiantes, el proceso de implantación comienza a los 16 (oveja) o 20 (vaca) días tras la cubrición, cuando el epitelio coriónico del embrión (formado por células del trofoblasto) desarrolla los cotiledones de origen fetal, los cuales se entrelazan con las carúnculas, cuyo origen es el endometrio materno.
La combinación de un cotiledón fetal y una carúncula materna se denomina placentoma, la unidad funcional de la placenta de los rumiantes (Figura 1A)3,6.
Por otra parte, las células del trofoblasto son componentes clave de la placenta, describiéndose dos poblaciones diferentes:
Células uninucleadas: forman la mayor parte de la interfaz feto-maternal y participan principalmente en el intercambio de nutrientes
Células binucleadas: participan en la síntesis de hormonas como el lactógeno placentario y la progesterona7,8 (Figura 1B)
La matriz extracelular (MEC) es otro componente importante de la placenta:
- Participa en la adhesión del trofoblasto al endometrio uterino Induce la diferenciación celular9
- Actúa como reservorio de factores de crecimiento10
- Sirve como vía por la que las células pueden migrar11
La MEC consiste en una mezcla de proteoglicanos, glicosaminoglicanos y componentes estructurales como diferentes tipos de colágeno, fibronectina y laminina, que son sintetizados principalmente por los fibroblastos.
Estas células también producen metaloproteinasas de la matriz (MMP), que degradan los componentes de la MEC y están reguladas por inhibidores tisulares de MMP; el desequilibrio de estas proteínas se ha asociado a diferentes condiciones patológicas y a la diseminación de determinados patógenos, entre ellos T. gondii, y de células infectadas a través de la barrera placentaria12,13.
| Tanto la gestación como el parto requieren una remodelación constante de la placenta que implica un delicado equilibrio entre la síntesis y la degradación de la MEC4. |
En cuanto a sus funciones, la placenta:
Forma una interfaz entre la circulación materna y la fetal, actuando así como sistema digestivo, respiratorio, de excreción, metabólico y endocrino del feto.
Secreta las hormonas necesarias para el mantenimiento de la gestación, la adaptación del metabolismo materno, el crecimiento fetal, el parto e incluso la lactancia.
Constituye una barrera física que protege al feto contra los gérmenes y fármacos que puedan circular por el torrente sanguíneo materno.
Sin embargo, algunos patógenos son capaces de atravesar esta barrera e infectar al feto debido a su reducido tamaño (p.ej., los virus), o a su capacidad de replicarse tanto en las células placentarias maternas como en las fetales (por ejemplo, T. gondii, N. caninum, Brucella abortus o Chlamydia abortus).
 El éxito de la gestación depende de una modulación inmunitaria precisa, capaz de proteger al feto de los agentes infecciosos, pero también de proporcionar un entorno receptivo para el desarrollo de un embrión semialogénico (que expresa antígenos extraños para la madre que son heredados por el padre).
|
No obstante, la modulación inmunitaria local que tiene lugar durante la gestación es un proceso complejo que todavía no se conoce completamente.Leer Interacciones placenta-patógeno en parásitos apicomplejos de rumiantes – Parte II
Adaptado y traducido del artículo original: “Modeling the ruminant placenta-pathogen interactions in apicomplexan parasites: current and future perspectives”, Pastor-Fernández I, Collantes-Fernández E, Jiménez-Pelayo L, Ortega-Mora LM and Horcajo P (2021); Front. Vet. Sci. 7:634458. doi: 10.3389/ fvets.2020.634458
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