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Home / Equine Research Bank / J Equine Sci / Circulating activin A during equine gestation and immunoloca...
Journal of equine science2021; 32(2); 39-48; doi: 10.1294/jes.32.39

Circulating activin A during equine gestation and immunolocalization of its receptors system in utero-placental tissues and fetal gonads.

Abstract: Although equine gestation is unique from the standpoint of fetal gonadal enlargement and regression, the activator of this process is still unknown. The present study aimed to show a possible role of activin during equine gestation. In the first experiment, weekly plasma samples from six pregnant mares were used to measure activin A. In the second experiment, eight pregnant mares carrying female (gestational days 110, 140, 180, and 270) and male fetuses (gestational days 120, 180, 225, and 314) were used for immunohistochemistry of activin receptors (IA, IB, IIA, IIB), and their intracellular mediators (Smad2, Smad3, Smad4). Activin A levels in maternal circulation remained low until fourth weeks of gestation, thereafter, started to increase, and peaked first at 11 weeks of gestation. The second significant peak was observed on the day of parturition. Activin receptors type IA, IB, IIA, and IIB were immunostained in interstitial and germ cells of fetal ovaries and testes along with utero-placental tissues. Smad2, Smad3, and Smad4 were also immunolocalized in all these organs. These results demonstrated the activin-producing capacity of utero-placental tissues, and also evidenced the existence of activin receptors and functional signaling molecules in these organs. The first increment in circulating activin A in maternal circulation coinciding with the timing of initiation of fetal gonadal enlargement suggests that activin from the utero-placental tissues may have a stimulatory role in fetal gonad enlargement and utero-placental development in mares, whereas the second peak could be important to follicular development in the maternal ovary for foal heat.
©2021 The Japanese Society of Equine Science.
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Publication Date: 2021-06-18 PubMed ID: 34220270PubMed Central: PMC8240525DOI: 10.1294/jes.32.39Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research analyzes the role of a hormone called activin A in horse gestation, its presence in maternal circulation, and its receptors in utero-placental tissues and fetal gonads. There is evidence that activin A might stimulate fetal gonad enlargement and utero-placental development, with a secondary peak indicating a potential role in follicular development in the maternal ovary.

Objective of the Study

  • The study aims to shed light on the role of activin, a hormone, during horse pregnancy, focusing on its potential to activate fetal gonadal enlargement – a unique feature of equine gestation.

Study Methods

  • The study has two parts. In the first part, weekly blood samples were collected from six pregnant mares to measure the levels of activin A. The second part involved detecting the presence of activin receptors in pregnant mares carrying both female and male fetuses at different gestational stages, along with their intracellular mediators (Smad2, Smad3, Smad4).

Findings

  • The levels of activin A in the mother’s circulation system remained low until the fourth week of gestation, following which they started to increase, peaking first at around the eleventh week.
  • The second significant peak was observed on the day of birth, possibly indicating the involvement of activin A in follicular development in the mother’s ovary during foal heat (the first estrus after foaling). The study discovered activin receptors (IA, IB, IIA, IIB) holistically across the utero-placental tissues and in fetal ovaries and testes.
  • The study also acknowledges the presence of functional signaling molecules like Smad2, Smad3, and Smad4 in these same organs.

Outcome of Study

  • These results not only demonstrate that utero-placental tissues can produce activin but also confirm the existence of activin receptors and signaling molecules in these organs.
  • The first significant increase in circulating activin A coinciding with the point of fetal gonadal enlargement implies an activating role activin might have in this enlargement process and in the development of utero-placental tissues.
  • The study therefore suggests that activin potentially plays a part in the unique processes witnessed during horse pregnancy, specifically the enlargement and regression of fetal gonads.

Cite This Article

APA
Dhakal P, Tsunoda N, Nambo Y, Taniyama H, Nagaoka K, Watanabe G, Taya K. (2021). Circulating activin A during equine gestation and immunolocalization of its receptors system in utero-placental tissues and fetal gonads. J Equine Sci, 32(2), 39-48. https://doi.org/10.1294/jes.32.39

Publication

Journal of equine science
ISSN: 1340-3516
NlmUniqueID: 9503751
Country: Japan
Language: English
Volume: 32
Issue: 2
Pages: 39-48

Researcher Affiliations

Dhakal, Pramod
  • Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
  • Division of Animal Science, University of Missouri, MO 65211, U.S.A.
Tsunoda, Nobuo
  • Shadai Corporation, Hokkaido 059-1432, Japan.
Nambo, Yasuo
  • United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.
  • Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido 080-8555, Japan.
Taniyama, Hiroyuki
  • Department of Veterinary Pathology, Rakuno Gakuen University, Hokkaido 069-8501, Japan.
Nagaoka, Kentaro
  • Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
  • United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.
  • Cooperative Division of Veterinary Sciences (Doctoral Program), Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Watanabe, Gen
  • Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
  • United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.
  • Cooperative Division of Veterinary Sciences (Doctoral Program), Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Taya, Kazuyoshi
  • Laboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
  • Shadai Corporation, Hokkaido 059-1432, Japan.

References

This article includes 44 references
  1. Allen W.R., Moor R.M.. The origin of the equine endometrial cups. I. Production of PMSG by fetal trophoblast cells.. J. Reprod. Fertil. 29: 313–316.
    pubmed: 5023705
  2. Arai K.Y., Tanaka Y., Taniyama H., Tsunoda N., Nambo Y., Nagamine N., Watanabe G., Taya K.. Expression of inhibins, activins, insulin-like growth factor-I and steroidogenic enzymes in the equine placenta.. Domest. Anim. Endocrinol. 31: 19–34.
    pubmed: 16233970
  3. Chen Y.G., Wang Q., Lin S.L., Chang C.D., Chuang J., Ying S.Y.. Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis.. Exp. Biol. Med. (Maywood) 231: 534–544.
    pubmed: 16636301
  4. Cole H.H., Hart G.H., Lyons W.R., Catchpole H.R.. The development and hormonal content of fetal horse gonads.. Anat. Rec. 56: 275–293.
  5. Debiève F., Hinck L., Biard J.M., Bernard P., Hubinont C.. Activin receptor expression and induction of apoptosis in rat blastocysts in vitro.. Hum. Reprod. 21: 618–623.
    pubmed: 16311291
  6. Ginther OJ. Embryology and placentation. 1992. pp. 345–417. In: Reproductive Biology of the Mare-basic and Applied Aspects, Equiservices, Madison.
  7. Ginther OJ. Endocrinology of pregnancy. 1992. pp. 419–456. In: Reproductive Biology of the Mare-basic and Applied Aspects, Equiservices, Madison.
  8. Ginther OJ. Parturition, pierperium and puberty. 1992. pp. 457–497. In: Reproductive Biology of the Mare-basic and Applied Aspects, Equiservices, Madison.
  9. Hasegawa Y., Miyamoto K., Abe Y., Nakamura T., Sugino H., Eto Y., Shibai H., Igarashi M.. Induction of follicle stimulating hormone receptor by erythroid differentiation factor on rat granulosa cell.. Biochem. Biophys. Res. Commun. 156: 668–674.
    pubmed: 3056399
  10. Hayashi K., Carpenter K.D., Gray C.A., Spencer T.E.. The activin-follistatin system in the neonatal ovine uterus.. Biol. Reprod. 69: 843–850.
    pubmed: 12748120
  11. Hoppen H.O.. The equine placenta and equine chorionic gonadotrophin-an overview.. Exp. Clin. Endocrinol. 102: 235–243.
    pubmed: 7995345
  12. Irvine C.H., Evans M.J.. FSH and LH concentrations preceding post-partum ovulation in the mare.. N. Z. Vet. J. 26: 310–311.
    pubmed: 284240
  13. Jarred R.A., Cancilla B., Richards M., Groome N.P., McNatty K.P., Risbridger G.P.. Differential localization of inhibin subunit proteins in the ovine testis during fetal gonadal development.. Endocrinology 140: 979–986.
    pubmed: 9927332
  14. Kimura Y., Sasaki M., Watanabe K., Dhakal P., Sato F., Taya K., Nambo Y.. Expression of activin receptors in the equine uteroplacental tissue: an immunohistochemical analysis.. J. Equine Sci. 29: 33–37.
    pmc: PMC6033615pubmed: 29991920
  15. Li R., Phillips D.M., Mather J.P.. Activin promotes ovarian follicle development in vitro.. Endocrinology 136: 849–856.
    pubmed: 7867593
  16. Lin T., Calkins J.K., Morris P.L., Vale W., Bardin C.W.. Regulation of Leydig cell function in primary culture by inhibin and activin.. Endocrinology 125: 2134–2140.
    pubmed: 2551638
  17. Ling N., Ying S.Y., Ueno N., Shimasaki S., Esch F., Hotta M., Guillemin R.. A homodimer of the beta-subunits of inhibin A stimulates the secretion of pituitary follicle stimulating hormone.. Biochem. Biophys. Res. Commun. 138: 1129–1137.
    pubmed: 3092817
  18. Mabuchi Y., Yamoto M., Minami S., Umesaki N.. The autocrine effect of activin A on human ovarian clear cell adenocarcinoma cells.. Oncol. Rep. 16: 373–379.
    pubmed: 16820918
  19. Mather J.P., Attie K.M., Woodruff T.K., Rice G.C., Phillips D.M.. Activin stimulates spermatogonial proliferation in germ-Sertoli cell cocultures from immature rat testis.. Endocrinology 127: 3206–3214.
    pubmed: 2249646
  20. Mathews L.S.. Activin receptors and cellular signaling by the receptor serine kinase family.. Endocr. Rev. 15: 310–325.
    pubmed: 8076584
  21. Medan M.S., Arai K.Y., Watanabe G., Taya K.. Inhibin: Regulation of reproductive function and practical use in females.. Anim. Sci. J. 78: 16–27.
  22. Meehan T., Schlatt S., O’Bryan M.K., de Kretser D.M., Loveland K.L.. Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH.. Dev. Biol. 220: 225–237.
    pubmed: 10753512
  23. Miró F., Smyth C.D., Hillier S.G.. Development-related effects of recombinant activin on steroid synthesis in rat granulosa cells.. Endocrinology 129: 3388–3394.
    pubmed: 1659530
  24. Nagamine N., Nambo Y., Nagata S., Nagaoka K., Tsunoda N., Taniyama H., Tanaka Y., Tohei A., Watanabe G., Taya K.. Inhibin secretion in the mare: localization of inhibin α, betaA, and betaB subunits in the ovary.. Biol. Reprod. 59: 1392–1398.
    pubmed: 9828183
  25. Nakamura M., Minegishi T., Hasegawa Y., Nakamura K., Igarashi S., Ito I., Shinozaki H., Miyamoto K., Eto Y., Ibuki Y.. Effect of an activin A on follicle-stimulating hormone (FSH) receptor messenger ribonucleic acid levels and FSH receptor expressions in cultured rat granulosa cells.. Endocrinology 133: 538–544.
    pubmed: 8393766
  26. Ohshima K., Ohshima K., Arai K.Y., Kishi H., Itoh M., Watanabe G., Terranova P.F., Arai K., Uehara K., Groome N.P., Taya K.. Potential role of activin A in follicular development during the second half of pregnancy in the golden hamster: utero-placental source of activin A.. J. Endocrinol. 172: 247–253.
    pubmed: 11834442
  27. Pangas S.A., Woodruff T.K.. Activin signal transduction pathways.. Trends Endocrinol. Metab. 11: 309–314.
    pubmed: 10996525
  28. Pashen R.L., Allen W.R.. The role of the fetal gonads and placenta in steroid production, maintenance of pregnancy and parturition in the mare.. J. Reprod. Fertil. Suppl. 27: 499–509.
    pubmed: 289829
  29. Petraglia F., Vaughan J., Vale W.. Inhibin and activin modulate the release of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone from cultured human placental cells.. Proc. Natl. Acad. Sci. USA 86: 5114–5117.
    pmc: PMC297567pubmed: 2662194
  30. Rabinovici J., Goldsmith P.C., Roberts V.J., Vaughan J., Vale W., Jaffe R.B.. Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads.. J. Clin. Endocrinol. Metab. 73: 1141–1149.
    pubmed: 1939530
  31. Reddy A., Suri S., Sargent I.L., Redman C.W.G., Muttukrishna S.. Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.. PLoS One 4: e4453.
    pmc: PMC2675175pubmed: 19412349
  32. Safi M., Onagbesan O.M., Volckaert G., Vanmontfort D., Bruggeman V., Decuypere E.. Developmental expression of activin/inhibin alpha- and beta(A)-subunit genes in the gonads of male and female chick embryos.. Gen. Comp. Endocrinol. 122: 304–311.
    pubmed: 11356042
  33. Samuel C.A., Allen W.R., Steven D.H.. Studies on the equine placenta. I. Development of the microcotyledons.. J. Reprod. Fertil. 41: 441–445.
    pubmed: 4452985
  34. Tanaka Y., Taniyama H., Tsunoda N., Herath C.B., Nakai R., Shinbo H., Nagamine N., Nambo Y., Nagata S., Watanabe G., Groome N.P., Taya K.. Localization and secretion of inhibins in the equine fetal ovaries.. Biol. Reprod. 68: 328–335.
    pubmed: 12493730
  35. Tanaka Y., Taniyama H., Tsunoda N., Shinbo H., Nagamine N., Nambo Y., Nagata S., Watanabe G., Herath C.B., Groome N.P., Taya K.. The testis as a major source of circulating inhibins in the male equine fetus during the second half of gestation.. J. Androl. 23: 229–236.
    pubmed: 11868816
  36. Tsuchida K., Sawchenko P.E., Nishikawa S., Vale W.W.. Molecular cloning of a novel type I receptor serine/threonine kinase for the TGF beta superfamily from rat brain.. Mol. Cell. Neurosci. 7: 467–478.
    pubmed: 8875430
  37. Tsunoda N., Machida N., Nagata S.I., Nagamine N., Nambo Y., Oikawa M., Taniyama H., Watanabe G., Taya K.. A morphometric study of interstitial cells in equine fetal gonads.. J. Reprod. Dev. 42: j91–j95.
  38. Turner D.D., Garcia M.C., Miller K.F., Holtan D.W., Ginther O.J.. FSH and LH concentrations in periparturient mares.. J. Reprod. Fertil. Suppl. 27: 547–553.
    pubmed: 289835
  39. Vale W., Rivier C., Hsueh A., Campen C., Meunier H., Bicsak T., Vaughan J., Corrigan A., Bardin W., Sawchenko P., Petraglia F., Yu J., Plotsky P., Spiess J., Rivier J.. Chemical and biological characterization of the inhibin family of protein hormones.. Recent Prog. Horm. Res. 44: 1–34.
    pubmed: 3064204
  40. Vale W., Rivier J., Vaughan J., McClintock R., Corrigan A., Woo W., Karr D., Spiess J.. Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid.. Nature 321: 776–779.
    pubmed: 3012369
  41. Wrana J.L., Attisano L., Wieser R., Ventura F., Massagué J.. Mechanism of activation of the TGF-beta receptor.. Nature 370: 341–347.
    pubmed: 8047140
  42. Xia Y., Schneyer A.L.. The biology of activin: recent advances in structure, regulation and function.. J. Endocrinol. 202: 1–12.
    pmc: PMC2704481pubmed: 19273500
  43. Yamanouchi K., Hirasawa K., Hasegawa T., Ikeda A., Chang K.T., Matsuyama S., Nishihara M., Miyazawa K., Sawasaki T., Tojo H., Tachi C., Takahashi M.. Equine inhibin/activin beta A-subunit mRNA is expressed in the endometrial gland, but not in the trophoblast, during pregnancy.. Mol. Reprod. Dev. 47: 363–369.
    pubmed: 9211420
  44. Zhang H., Nagaoka K., Imakawa K., Nambo Y., Watanabe G., Taya K., Weng Q.. Expression of inhibin/activin subunits in the equine uteri during the early pregnancy.. Reprod. Domest. Anim. 48: 423–428.
    pubmed: 23043254
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