Implicación del receptor mu opioide (MOR) en la maduración ovocitaria, la capacitación de espermatozoides y el endometrio durante el ciclo menstrual.

213 p.El sistema opioide está involucrado en la mayor parte de los procesos implicados en la reproducción y una desregulación de cualquiera de sus componentes, tanto por agentes exógenos como por patologías propias, podría provocar una disfuncionalidad del aparato reproductor. Por ello es importante conocer en qué procesos los opioides ejercen una regulación y las vías por las cuales la llevan a cabo. El objetivo de esta tesis es contribuir al conocimiento del sistema opioide, en concreto del receptor mu opioide (MOR), en el sistema reproductor haciendo una aproximación tanto descriptiva como funcional en tres procesos clave de la reproducción: la maduración de los ovocitos, la capacitación de los espermatozoides y el ciclo endometrial. Los resultados obtenidos en esta tesis indican que MOR está presente e involucrado en la regulación de la maduración ovocitaria, la capacitación de los espermatozoides y el ciclo endometrial. En cada uno de estos eventos, tanto la presencia/localización como la regulación ejercida por MOR varía, sugiriendo una regulación en su función dependiendo del proceso en el que actúe e incluso del momento del ciclo reproductivo. Estos resultados son de gran importancia debido a la amplia exposición a fármacos opiáceos frente a la que nos encontramos hoy en día. Además, abren nuevas vías de investigación en la prevención de la esterilidad, en el desarrollo de nuevas técnicas terapéuticas parapatologías en las que el sistema opioide esté relacionado y en la mejora de las técnicas de reproducción asistida actuales

Delta and kappa opioid receptors in human endometrium during the menstrual cycle: Expression and localization

Objective Endogenous opioid peptides were reported to be involved in the regulation of reproductive physiology and their precursors and receptors were described in many of the male and female reproductive tissues. Mu opioid receptor (MOR) was described in human endometrial cells and its expression and localization changed during the menstrual cycle. However, there is no data from the distribution of the other opioid receptors: Delta (DOR) and Kappa (KOR). The objective of the present work was to analyze the dynamics of expression and localization of DOR and KOR in human endometrium throughout the menstrual cycle. Study design Human endometrial samples from different menstrual cycle phases were analyzed by immunohistochemistry. Results DOR and KOR were present in all samples analyzed and the protein expression and localization changed throughout the menstrual cycle. Both receptor expression increased during the late proliferative phase and decreased during the late secretory-one, especially in the luminal epithelium. DOR expression was generally higher than KOR expression in all cell compartments. Conclusions The presence of DOR and KOR in human endometrium and their dynamic changes during the menstrual cycle join the results previously obtained in MOR suggesting a possible role of opioids in reproduction events related to the human endometrium.The authors thank Leire Andrés (Cruces University Hospital) and Edurne Alonso (UPV/EHU) for help in the discussion on endometrial histology. This work received financial support from the University of the Basque Country (Grant PPGA19/04). E.O. carried out all the experimentation without any public or private financial help. L.T. acknowledges the financial support given by University of the Basque Country (PIF15/149). The authors also thank Ane Portillo for technical help in analysing the results

Obozitoak in vitro heltzeko teknika (IVM): enbrioiaren garapen egokirako erronka

Oocyte’s maturation is a very important process in fertility because it is necessary for subsequent fertilization. In addition, maturation process influences the embryo, since the quality of the developing embryo is directly related to the maturity and the quality of the oocyte. This growth culminates just prior to ovulation during oocyte maturation. Adequate nuclear and cytoplasmic changes associated with maturation process of oocytes are fundamental for correct ovulation and subsequent fertilization. One of the main challenges is to determine the molecular pathways that regulate that maturation process. In addition, to better understanding female reproductive physiology, we could help to optimize the reproductive techniques by modulating the process of oocyte in vitro maturation, through the IVM technique. This technique consists in turning immature oocytes to mature exogenously in a culture media supplemented with different molecules to promote maturation. The most important advantage of IVM method is that could be the only hope or, at least, an alternative for a high number of patients unable to tolerate high doses of gonadotropins. Among the ARTs, the in vitro maturation oocytes (IVM) is less developed than other techniques, but its implementation would entail a qualitative advance.; Ugaztun emeen obozitoen heltze-prozesua ugalkortasunean garrantzi handia duen prozesua da, obulua ernaldua izateko ezinbestekoa delako. Gainera, heltze-prozesuak baldintzatzen du sortu behar den izaki berria, garapen-bidean dagoen enbrioiaren kalitatea zuzenean lotuta baitago obozitoaren heldutasunarekin eta kalitatearekin. Izan ere, obozitoen heltze-prozesuarekin erlazionatutako aldaketa nuklear eta zitoplasmatiko egokiak funtsezkoak dira obulazio eta haren ondorengo ernalketa zuzen baterako. Erronka nagusietariko bat da, beraz, heltze-prozesuan garrantzitsuak diren seinaleztapen-bidezidorrak eta elkarrekintza konplexuak zehaztea. Horrela, emakumezkoen ugal-fisiologia hobeto ulertzeaz gain, obozitoen in vitro heltze-prozesua modulatuz, lagunduriko ugalketa-teknikak optimizatzen lagundu genezakeelako: besteak beste, obozitoak in vitro heltzeko (IVM) teknika. Teknika horren bidez, pazienteari oraindik helduta ez dauden obozitoak erauzten zaizkio eta exogenoki heltzen dira hazkuntza-inguruneetan. Modu horretan, albo-kalte ugari eragiten dituen gonadotropinak hartzea saihesten da, eta hormonazioa kontraindikaturik daukaten emakumeentzat haurdun geratzeko aukera bakarrenetarikoa da. Teknika horren ezarpenak aurrerapen ugari dakartzan arren (esaterako, albo-kalte eta kostu ekonomiko gutxiago), oraindik gutxi erabiltzen da, beste ugal-tekniken arrakasta-mailara heldu ez delako