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Role of the superior ovarian nerve in the regulation of follicular development and steroidogenesis in the morning of diestrus 1

  • Reproductive physiology and disease
  • Published:
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Abstract

Purpose

Little is known about the role of the superior ovarian nerve (SON) in follicular development during the estrus cycle. The aim of the present study was to analyze the role of neural signals arriving through the SON at the ovaries in the regulation of follicular development and ovarian steroid secretion in diestrus 1 of cyclic rats.

Methods

Cyclic rats were subjected to left, right, or bilateral SON sectioning or to unilateral or bilateral laparotomy at diestrus 1 at 11:00 h. Animals were sacrificed 24 h after surgery.

Results

Compared to laparotomized animals, unilateral SON sectioning decreased the number of preovulatory follicles, while bilateral SON sectioning resulted in a decreased number of atretic preantral follicles. An important observation was the presence of invaginations in the follicular wall of large antral and preovulatory follicles in animals with denervation. Furthermore, left SON sectioning increased progesterone levels but decreased testosterone levels, which are effects that were not observed in animals that were subjected to right denervation.

Conclusions

At 11:00 h of diestrus 1, the SON was found to stimulate follicle development, possibly via neural signals, such as noradrenaline and/or vasoactive intestinal peptide, and this stimulation induced the formation of follicle-stimulating hormone receptors. The role of the SON in the regulation of ovarian steroid secretion is asymmetric: the left SON inhibits the regulation of progesterone and stimulates testosterone secretion, and the right nerve does not participate in these processes.

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References

  1. Burden WH. The adrenergic innervation of mammalian ovaries. In: Ben-Jonathan N, Bahr JM, Weiner RI, editors. Catecholamines as hormone regulators. New York: Raven Press; 1985. p. 261–78.

    Google Scholar 

  2. Doganay M, Simsek A, Tapisiz OL, Mulazimoglu BS, Yumusak N, Gungor T. Superior ovarian nerve (SON) transaction leads to stunted follicular maturation: a histomorphologic and morphometric analysis in the rat model. Fertil Steril. 2010;93(5):1711–4.

    PubMed  Google Scholar 

  3. Dissen GA, Ojeda SR. Ovarian innervation. In: Knobil E, Neill JD, editors. Encyclopedia of reproduction. USA: Academic Press; 1999. pp. 583–589.

  4. Lawrence IE Jr, Burden HW. The origin of the extrinsic adrenergic innervation to the rat ovary. Anat Rec. 1980;196:51–9.

    CAS  PubMed  Google Scholar 

  5. Aguado LI, Ojeda SR. Prepuberal ovarian function is finely regulated by direct adrenergic influences. Role of noradrenergic innervation. Endocrinology. 1984;114(5):1845–53.

    CAS  PubMed  Google Scholar 

  6. Aguado LI, Ojeda SR. Ovarian adrenergic nerves play a role in maintaining preovulatory steroid secretion. Endocrinology. 1984;114(5):1944–6.

    CAS  PubMed  Google Scholar 

  7. Selstam G, Norjavaara E, Tegenfelt T, Lundberd S, Sandström C, Persson S. Partial denervation of the ovaries by transaction of the suspensory ligament does not inhibit ovulation in rats treated with pregnant mare serum gonadotropin. Anat Rec. 1984;213:392–5.

    Google Scholar 

  8. Chávez R, Carrizosa L, Dominguez R. Effects of superior ovarian nerve section on spontaneous and induced ovulation in adult rats. Med Sci Res. 1991;19:41–2.

    Google Scholar 

  9. Morales L, Chávez R, Domínguez R. Participation of the superior ovarian nerve in the regulation of ovulation in the prepubertal rat: differential effects of unilateral an bilateral section of the nerve. Med Sci Res. 1993;21:15–7.

    Google Scholar 

  10. Morales-Ledesma L, Vieyra E, Ramírez DA, Trujillo A, Chavira R, Cárdenas M, et al. Effects on steroid hormones secretion resulting from the acute stimulation of sectioning the superior ovarian nerve to pre-pubertal rats. Reprod Biol Endocrinol. 2012;10:88.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhang X, Zhang L, Huo S, Wang J, Cui S. Neonatal superior ovarian nerve transection inhibits follicle development by enhancing follicular atresia and suppressing granulose cell proliferation in rats. Reprod Fertil Dev. 2010;22:1148–58.

    PubMed  Google Scholar 

  12. Rosas G, Linares R, Ramírez DA, Vieyra E, Trujillo A, Domínguez R, et al. The neural signals of the superior ovarian nerve modulate in an asymmetric way the ovarian steroidogenic response to the vasoactive intestinal peptide. Front Physiol. 2018;9:1142.

    PubMed  PubMed Central  Google Scholar 

  13. Sosa Z, Delgado M, Casais M, Aguado L, Rastrilla AM. Release of ovarian progesterone during the rat oestrous cycle by ganglionic cholinergic influence. The role of norepinephrine. J Steroid Biochem Mol Biol. 2004;91:179–84.

    CAS  PubMed  Google Scholar 

  14. Delgado M, Sosa Z, Dominguez N, Casais M, Aguado L, Rastrilla AM. Effect of the relation between neural cholinergic action and nitric oxide on ovarian steroidogenesis in prepubertal rats. J Steroid Biochem Mol Biol. 2004;91:139–45.

    CAS  PubMed  Google Scholar 

  15. Delgado M, Casais M, Sosa Z, Rastrilla A. Ganglionic adrenergic action modulates ovarian steroid and nitric oxide in prepubertal rat. Endocr J. 2006;53:547–54.

    CAS  PubMed  Google Scholar 

  16. Delgado SM, Escudero CG, Casais M, Gordillo M, Anzulovich AC, Sosa Z, et al. Ovaric physiology in the first oestral cycle: influence of noradrenergic and cholinergic neural stimuli from coelic ganglion. Steroids. 2010;75:6585–694.

    Google Scholar 

  17. Erskine MS, Weaver CE Jr. The role of ovarian sympathetic innervation in the control of estrous responsiveness in the rat. Horm Behav. 1988;22:1–11.

    CAS  PubMed  Google Scholar 

  18. Flores A, Velasco J, Gallegos AI, Mendoza FD, Everardo PM, Cruz ME, et al. Acute effects of unilateral sectioning the superior ovarian nerve of rats with unilateral ovariectomy on ovarian hormones (progesterone, testosterone and estradiol) levels vary during the estrous cycle. Reprod Biol Endocrinol. 2011;9:34–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Klein CM, Burden HW. Anatomical localization of afferent and postganglionic sympathetic neurons innervating the rat ovary. Neurosci Lett. 1988;85:217–22.

    CAS  PubMed  Google Scholar 

  20. Forneris ML, Aguado LI. Neonatal superior ovarian nerve transection disturbs the cyclic activity of the female rats. J Steroid Biochem Mol Biol. 2002;82:75–82.

    CAS  PubMed  Google Scholar 

  21. Gerendai I, Kocsis K, Halász B. Supraspinal connections of the ovary: structural and functional aspects. Microsc Res Tech. 2002;59(6):474–83.

    PubMed  Google Scholar 

  22. Gerendai I, Tóth IE, Boldogköi Z, Halász B. Recent findings on the organization of central nervous system structures involved in the innervation of endocrine glands and other organs; observations obtained by the transneuronal viral double-labeling technique. Endocrine. 2009;36:179–88.

    CAS  PubMed  Google Scholar 

  23. Tóth IE, Wiesel O, Boldogkói Z, Bálint K, Tapaszti Z, Gerendai I. Predominant innervation of the left ovary. Microsc Res Tech. 2007;70:710–8.

    PubMed  Google Scholar 

  24. Ramírez DA, Vieyra E, González AI, Morán C, Domínguez R, Morales-Ledesma L. Both the suprachiasmatic nucleus and the superior ovarian nerve contribute to the processes of ovulation and steroid hormone secretion on proestrus. Reprod Sci. 2017;24(6):844–55.

    PubMed  Google Scholar 

  25. Morán C, Morales L, Quiróz U, Domínguez R. Effects of unilateral or bilateral superior ovarian nerve section in infantile rats on follicular growth. J Endocrinol. 2000;166:205–11.

    PubMed  Google Scholar 

  26. Trujillo A, Riboni L. Effects of functional peripheral sympathetic denervation induced by guanethidine on follicular development and ovulation of the adult female guinea-pig. Gen Comp Endocrinol. 2002;127:273–8.

    CAS  PubMed  Google Scholar 

  27. Sosa ZY, Casais M, Rastrilla AM, Aguado L. Adrenergic influences on coeliac ganglion affect the release of progesterone from cycling ovaries: characterisation of an in vitro system. J Endocrinol. 2000;166:307–18.

    CAS  PubMed  Google Scholar 

  28. Hirshfield AN. Development of follicles in the mammalian ovary. Int Rev Cytol. 1991;124:43–101.

    CAS  PubMed  Google Scholar 

  29. Butcher RY, Kirkpatrick-Keller D. Patterns of follicular growth during the four-day estrous cycle of the rat. Biol Reprod. 1984;31:280–6.

    CAS  PubMed  Google Scholar 

  30. Linares R, Rosas G, Vieyra E, Ramírez DA, Velázquez D, Espinoza JA, et al. In adult rats with polycystic ovarian syndrome, unilateral or bilateral vagotomy modifies the noradrenergic concentration in the ovaries and the celiac superior mesenteric ganglia in different ways. Front Physiol. 2019;10:1309.

    PubMed  PubMed Central  Google Scholar 

  31. Flores A, Meléndez G, Palafox MT, Rodríguez JO, Barco AI, Chavira R, Domínguez R y Cruz ME. The participation of the cholinergic system in regulating progesterone secretion through the ovarian-adrenal crosstalk varies along the estrous cycle. Endocrine. 2005;(28)2:1–7.

  32. Flores A, Rodríguez JO, Palafox MT, Meléndez G, Barco AI, Chavira R, et al. The acute asymmetric effects of hemiovariectomy on testosterone secretion vary long the estrous cycle. The participation of the cholinergic system. Reprod Biol Endocrinol. 2006;4:1–10.

    Google Scholar 

  33. Cruz ME, Flores A, Palafox MT, Meléndez G, Rodriguez JO, Chavira R, et al. The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model. Reprod Biol Endocrinol. 2006;4(43):1–8.

    Google Scholar 

  34. Flores A, Gallegos AI, Velasco J, Mendoza D, Everardo PM, Cruz ME, et al. The acute effects of bilateral ovariectomy or adrenalectomy on progesterone, testosterone and estradiol serum levels depend on the surgical approach and the day of the estrous cycle when they are performed. Reprod Biol Endocrinol. 2008;6:1–7.

    Google Scholar 

  35. Uchida S, Kagitani F, Hotta H, Hanada T, Aikawa Y. Cutaneous mechanical stimulation regulates ovarian blood flow via activation of spinal and supraspinal reflex pathways in anesthetized rats. Jap J Physiol. 2005;55:265–77.

    Google Scholar 

  36. Barco AI, Flores A, Chavira R, Damián-Matsumura P, Domínguez R, Cruz ME. Asymmetric effects of acute hemiovariectomy on steroid hormone secretion by the in situ ovary. Endocrine. 2003;21:209–15.

    CAS  PubMed  Google Scholar 

  37. Fohr KJ, Mayerhofer A, Sterzik K, Rudolf M, Rosenbusch B, Gratzl M. Concerted action of human chorionic-gonadotropin and norepinephrine on intracellular-free calcium in human granulosa-lutein cells-evidence for the presence of a functional alpha-adrenergic receptor. J Clin Endocrinol Metab. 1993;76:367–73.

    CAS  PubMed  Google Scholar 

  38. Mayerhofer A, Dissen GA, Costa ME, Ojeda SR. A role for neurotransmitters in early follicular development: induction of functional follicle-stimulating hormone receptors in newly formed follicles of the rat ovary. Endocrinology. 1997;138:3320–9.

    CAS  PubMed  Google Scholar 

  39. Garraza MH, Aguado LI, De Bortoli MA. In vitro effect of neuropeptides on ovary or celiac ganglion affects the release of progesterone from ovaries in the rat. Med Sci Monit. 2004;10(12):BR440–6.

    CAS  PubMed  Google Scholar 

  40. Davoren JB, Hsueh AJW. Vasoactive intestinal peptide: a novel stimulator of steroidogenesis by cultured rat granulosa cells. Biol Reprod. 1985;33:37–52.

    CAS  PubMed  Google Scholar 

  41. George FW, Ojeda SR. Vasoactive intestinal peptide enhances aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone. Proc Natl Acad Sci U S A. 1987;84:5803–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Johnson AL, Li Z, Gibney JA, Malamed S. Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17a-hydroxylase enzyme activity in hen granulosa cells. Biol Reprod. 1994;51:327–33.

    CAS  PubMed  Google Scholar 

  43. Weiss GK, Dail WG, Ratner A. Evidence for direct neural control of ovarian steroidogenesis in rats. J Reprod Fertil. 1982;65:507–11.

    CAS  PubMed  Google Scholar 

  44. Kagitani F, Uchida S, Hotta H. Effects of electrical stimulation of the superior ovarian nerve and the ovarian plexus nerve on the ovarian estradiol secretion rate in rats. J Physiol Sci. 2008;58:133–8.

    CAS  PubMed  Google Scholar 

  45. Kagitani F, Uchida S, Hotta H. The role of alpha adrenoceptors in the vascular and estradiol secretory responses to stimulation of the superior ovarian nerve. J Physiol Sci. 2011;61:247–51.

    CAS  PubMed  Google Scholar 

  46. Uchida S, Kagitani F. Effects of electrical stimulation of autonomic nerves to the ovary on the ovarian testosterone secretion rate in rats. Auton Neurosci. 2014;180:48–52.

    CAS  PubMed  Google Scholar 

  47. Uchida S. Sympathetic regulation of estradiol secretion from the ovary. Auton Neurosci. 2015;187:27–35.

    CAS  PubMed  Google Scholar 

  48. Rosas NH, Santiago ML, Zárate A, Angulo M, Flores A, Cruz-Morales SE, et al. Aromatase, 3β and 17β-hydroxysteroid dehydrogenase genes’ expression in the ovaries varies during the estrous cycle, is asymmetric and depends on the superior ovarian nerve innervation. SM J Steroids Horm. 2018;1(1):1002.

    Google Scholar 

  49. Advis JP, Ahmed CE, Ojeda SR. Direct hypothalamic control of vasoactive intestinal peptide (VIP) levels in the developing rat ovary. Brain Res Bull. 1989;22:605–10.

    CAS  PubMed  Google Scholar 

  50. Dees WL, Ahmed CE, Ojeda SR. Substance P and vasoactive intestinal peptide-containing fibers reach the ovary by independent routes. Endocrinology. 1986;119:638–41.

    CAS  PubMed  Google Scholar 

  51. Escobar-Sánchez ML, Echeverría-Martínez OM, Vázquez-Nin GH. Immunohistochemical and ultrastructural visualization of different routes of oocyte elimination in adult rats. Eur J Histochem. 2012;56:e17.

    PubMed  PubMed Central  Google Scholar 

  52. Burghardt RC, Matheson RL. Gap junction amplification in rat ovarian granulosa cells. I. A direct response to follicle-stimulating hormone. Dev Biol. 1982;94(1):206–15.

    CAS  PubMed  Google Scholar 

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Acknowledgments

We want to thank the “Posgrado en Ciencias Biológicas, UNAM” and CONACyT for the support to carry out this study. The authors thank Roberto Chavira and Mario Cardenas for their help with performing the RIAs to measure steroid and gonadotrophic hormone levels.

Funding

This work was supported by UNAM-DGAPA-PAPIIT [grant IN-216519] and CONACyT [grant 220291].

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Authors

Contributions

DAR, RD, and LM-L designed the experiments. DAR and EV performed the experiments. DAR, EV, GR, RL, JAE, ACHO, RD, and LM-L devised the study, participated in the discussion of the results, and co-wrote the manuscript. All authors read and approved the final version of this manuscript.

Corresponding author

Correspondence to Leticia Morales-Ledesma.

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The authors declare that they have no conflict of interest.

Ethical approval

All experiments were carried out in strict accordance with the Mexican Law of Animal Treatment and Protection Guidelines and followed the Mexican Official Standard NOM-062-ZOO-1999 specifications. All efforts were made to minimize the number of animals used and their suffering.

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Ramírez Hernández, D.A., Vieyra Valdez, E., Rosas Gavilán, G. et al. Role of the superior ovarian nerve in the regulation of follicular development and steroidogenesis in the morning of diestrus 1. J Assist Reprod Genet 37, 1477–1488 (2020). https://doi.org/10.1007/s10815-020-01787-6

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  • DOI: https://doi.org/10.1007/s10815-020-01787-6

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