Acción de la prolactina sobre la función ovárica durante la gestación de Lagostomus maximus (Rodentia: Chinchillidae)
The South America plains vizcacha, Lagostomus maximus, is an histricogmorph caviomorph rodent autochthonous of Argentina. The vizcacha has a biannual reproductive cycle and a gestation period of approximately 155 days. Its gestation is characterized by the implantation of 10 to 12 embryos, which und...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Ciencias Veterinarias
2021
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=avaposgra&cl=CL1&d=HWA_8080 https://repositoriouba.sisbi.uba.ar/gsdl/collect/avaposgra/index/assoc/HWA_8080.dir/8080.PDF |
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| Sumario: | The South America plains vizcacha, Lagostomus maximus, is an histricogmorph caviomorph rodent autochthonous of Argentina. The vizcacha has a biannual reproductive cycle and a gestation period of approximately 155 days. Its gestation is characterized by the implantation of 10 to 12 embryos, which undergo a progressive and selective natural reabsorption, and only the 2 embryos located closest to the cervix complete their development. This characteristic would be related to a deficient production of placental progesterone (P4) due to its early calcification, so the P4 necessary to sustain the viability of these embryos would come from the ovaries, specifically from the corpora lutea (CL). Furthermore, our group has previously described that around the day 70 of gestation, the vizcacha undergoes a marked hormonal decrease that enables the reactivation of the hypothalamic-pituitary-ovarian (HPO) axis and results in a pseudo-ovulation process that promotes luteinization and the formation of a set of accessory corpora lutea (aCL). This could help restore the ovarian steroid levels and thus to carry the pregnancy to term.
Considering that PRL plays a key role in the production of luteal P4 during the gestation of murines, in the present thesis it was proposed that in the case of the vizcacha, PRL participates in the modulation of its reproductive axis by targeting the ovary and promoting the secretion of luteal P4, and also, by targeting the hypothalamic-pituitary axis and promoting the secretion of luteinizing hormone (LH). To test this hypothesis, the existence of a functional relationship between PRL and the ovulatory event at mid-gestation, the variant of the PRL receptor involved in modulating this event, as well as the role of PRL in the regulation of the hypothalamic-pituitary activity of L. maximus were investigated.
For this, pregnant and non-pregnant adult female vizcachas were used. Various experimental techniques such as ovarian explant culture, ovulation induction in pregnant females (OIP), and an effective induced hyperprolactinemia (H-PRL) model were developed. The ovarian proteomic analysis was performed for the first time for this specie.
Using morphological, immunohistochemical and functional technics, both the steroidogenic reactivation of the primary CL (pCL) and the steroidogenic activity in the aCL immediately after the reactivation of the HPO axis during pregnancy were determined. Moreover, the participation of PRL in this process could be established.
Specifically, the increased expressions of steroidogenic enzymes and of the angiogenesis marker VEGF were determined. Both the size of luteal structures and the immunoreactive areas for steroidogenic enzymes revealed that, of the luteal structures, the pCL are the main contributors to the restoration of P4 levels. On the other hand, by using an induced hyperprolactinemia model, the active role of PRL in the ovarian function was determined, and its ability to stimulate both the expression of steroidogenic enzymes and the luteogenesis process were confirmed. This PRLinduced activity would occur through the prolactin receptor long variant since its effects were suppressed by the Janus kinase inhibitor AG490. In ovarian explants of OIP stimulated with PRL, steroidogenic response was not detected. The fact that PRL induced significant increases in aromatase activity and LH receptor (LHR) in antral follicles suggests that PRL would exert its stimulation prior the reactivation of the HPO axis during pregnancy. Such earlier participation would be key in increasing the antral follicles sensitivity to the imminent increase of LH as result of the reactivation of the HPO axis during pregnancy. The analysis of the ovarian proteome of H-PRL animals compared with their controls indicated that, in addition to its role as a modulator of ovarian steroidogenesis, PRL also induces the expression of various tissue remodeling factors. Therefore, PRL targets the ovary of the vizcachas before hypothalamicpituitary reactivation and mediates multiple actions through the long form of its receptor, such as regulating ovarian activity by inducing maturation of the antral follicles and favoring the steroidogenic reactivation of pCL and the aCL formation.
Likewise, it is important to note that the results obtained in this work indicate that the ovarian activity would be favored by hypothalamic-pituitary reactivation. PRL was shown to regulate the release of gonadotropin-releasing hormone (GnRH) and LH in a dose-dependent manner, with increased release of these hormones stimulated by moderate levels of PRL and inhibition induced by high levels of this hormone. It should be noted that, unlike what has been described in other mammals, the GnRH neurons of the vizcacha express PRL receptor, which would favor the direct regulation of GnRH expression and release by PRL.
Thus, it could be concluded that in Lagostomus maximus, PRL would be a key hormone in the regulation of the pseudo-ovulation process at mid-pregnancy. It would participate in the reactivation of the HPO axis, and ultimately result in an increase in P4 levels, which are essential to complete their development of the two embryos that escaped the reabsorption process. |
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