Advertisement

Differential effects of 5α-norethisterone on the histomorphology of the oviduct and uterus of the pregnant rabbit

      Abstract

      In this study, the histomorphological changes induced by 5α-norethisterone (5α-NET), a reduced metabolite of the contragestational postcoital agent norethisterone, in the oviduct and the uterus of the pregnant rabbit were determined. Adult fertilized rabbits were treated daily with 5α-NET (1.0, 1.5, 2.5, and 5.0 mg/kg/day) during 7 consecutive days, starting from the first day after coitus. Twenty-four hours after the last administration, the histological analysis of the oviduct and the uterus was performed. It was observed that in the infundibulum-ampullae region as well as in the isthmus of the oviduct, the number of nonsecretory cells (PAS-negative) were decreased, whereas the number of secretory cells (PAS-positive) were increased significantly after 5α-NET administration. The proportion of glandular tissue in the uterus markedly diminished in relation to that of the stromal tissue. This indicates an inhibition of the endometrial transformation observed during normal pregnancy. Interestingly, the highest doses of 5α-NET (2.5 and 5.0 mg/kg/day) induced necrosis in the uterus but not in the oviduct. These results suggest that the molecular antiprogestational effects previously observed after 5α-NET administration are also related to changes in the histomorphology of both the oviduct and the uterus of the pregnant rabbit.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lei H.P.
        • Hu Z.P.
        The mechanisms of action of vacation pills.
        in: Fen C.C. Griffin D. Woolman A. Recent Advances in Fertility Regulation. Atar SA, Geneva1981: 70-82
        • Larrea F.
        • Vilchis F.
        • Chávez B.
        • Pérez A.E.
        • Garza-Flores J.
        • Pérez-Palacios G.
        The metabolism of 19-nor contraceptive progestins modulate their biological activity at the neuroendocrine level.
        J Steroid Biochem. 1987; 27: 657-663
        • Pérez-Palacios G.
        • Chávez B.
        • Escobar N.
        • et al.
        Mechanisms of action of contraceptive synthetic progestins.
        J Steroid Biochem. 1981; 15: 125-130
        • Pérez-Palacios G.
        • Cerbón M.A.
        • Pasapera A.M.
        • et al.
        Mechanisms of hormonal and antihormonal action of contraceptive progestins at the molecular level.
        J Steroid Biochem Mol Biol. 1991; 41: 479-485
        • Chávez B.
        • Vilchis F.
        • Pérez A.E.
        • Garcı́a G.A.
        • Grillasca Y.
        • Pérez-Palacios G.
        Stereospecificity of the intracellular binding of norethisterone and its A-ring reduced metabolites.
        J Steroid Biochem. 1985; 22: 121-126
        • Cerbón M.A.
        • Pasapera A.M.
        • Gutierrez-Sagal R.
        • Garcı́a G.A.
        • Pérez-Palacios G.
        Variable expression of the uteroglobin gene following the administration of norethisterone and its A-ring reduced metabolites.
        J Steroid Biochem. 1990; 36: 1-6
        • Pasapera A.M.
        • Cerbón M.A.
        • Castro I.
        • et al.
        Norethisterone metabolites modulate the uteroglobin and progesterone receptor gene expression in prepubertal rabbits.
        Biol Rep. 1995; 52: 426-432
        • Castro I.
        • Cerbón M.A.
        • Pasapera A.M.
        • et al.
        Molecular mechanisms of the antihormonal and antiimplantation effects of norethisterone and its A-ring reduced metabolites.
        Mol Reprod Dev. 1995; 40: 157-163
        • Bowers A.
        • Ringold H.J.
        • Denot E.
        Steroids C1 19-nor-dihydro-testosterone derivatives.
        J Am Chem Soc. 1958; 80: 6115-6121
      1. Schubert K, Stolzner W, Freund R, Kurischko A, Koch M, Freund H. Endocrinological investigation of 5α-dihydro-norethisterone (5α-DH-NET). Interim Progress Report. Central Institute of Microbiology and Experimental Therapy Academy of Sciences of the G.D.R, 1983.

        • Fredricsson B.
        • Björkman N.
        Morphologic alteration in the human oviduct epithelium induced by contraceptive methods.
        Fertil Steril. 1973; 24: 19-30
        • Oberti C.
        • Dabancens A.
        • Garcı́a-Huidobro M.
        • Rodrı́guez-Bravo R.
        • Zanartu J.
        Low dosage oral progesterone to control fertility. II. Morphologic modifications in the gonad and oviduct.
        Obstet Gynecol. 1974; 43: 285-294
        • Hyde B.A.
        • Blaustein J.D.
        • Black D.L.
        Differential regulation of progestin receptor immunoreactivity in the rabbit oviduct.
        Endocrinology. 1989; 125: 1479-1483
        • Perrot-Applanat M.
        • Logeat F.
        • Groyer-Picard M.T.
        • Milgrom E.
        Immunocytochemical study of mammalian progesterone receptor using monoclonal antibodies.
        Endocrinology. 1985; 116: 1473-1484
        • Davies J.
        • Hoffman L.H.
        Studies on the progestational endometrium of the rabbit; light microscopy, day 0 to day 13 of gonadotrophin induced pseudopregnancy.
        Am J Anat. 1975; 137: 423-446
        • Koering M.J.
        • Healy D.L.
        • Hodgen G.D.
        Morphologic response of endometrium to a progesterone receptor antagonist, RU-486, in monkeys.
        Fertil Steril. 1986; 45: 280-287
        • Perrot-Applanat M.
        • Groyer-Picard M.
        • Garcı́a E.
        • Lorenzo F.
        • Milgrom E.
        Immunocytochemical demonstration of estrogen and progesterone receptors in muscle cells of uterine arteries in rabbits and humans.
        Endocrinology. 1988; 123: 1511-1519
        • Camacho-Arroyo I.
        • Ruiz A.
        • Gamboa-Domı́nguez A.
        • Pérez-Palacios G.
        • Cerbón M.A.
        Immunohistochemical localization of intracellular progesterone and glucocorticoid receptors in the rabbit lung.
        J Endocrinol. 1994; 142: 311-316
        • Pang X.
        • Cotreau-Bibbo M.M.
        • Sant G.R.
        • Theoharides T.C.
        Bladder mast cells expression of high affinity oestrogen receptors in patients with interstitial cystitis.
        Br J Urol. 1995; 75: 154-161
        • Gibbons A.F.E.
        • Chang M.C.
        Number of mast cells in the rat uterus with special reference to its relation to hormonal treatment and decidual response.
        Biol Reprod. 1972; 6: 193-203
        • Kim-Bjorklund T.
        • Landgren B.M.
        • Johannisson E.
        Morphometric studies of the endometrium, the fallopian tube and the corpus luteum during contraception with 300 μg norethisterone (NET) minipill.
        Contraception. 1991; 43: 459-475