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Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens

Published online by Cambridge University Press:  03 June 2016

L. Paixão ,
L. M. Velez ,
B. R. Santos ,
C. Tusset ,
S. B. Lecke ,
A. B. Motta  and
P. M. Spritzer
L. Paixão
Affiliation:
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
L. M. Velez
Affiliation:
Laboratorio de Fisio-patología Ovárica, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires, Buenos Aires, Argentina
B. R. Santos
Affiliation:
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
C. Tusset
Affiliation:
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
S. B. Lecke
Affiliation:
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Diagnostic Methods, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
A. B. Motta
Affiliation:
Laboratorio de Fisio-patología Ovárica, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires, Buenos Aires, Argentina
P. M. Spritzer*
Affiliation:
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Laboratory of Molecular Endocrinology, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
*
*Address for correspondence: P. M. Spritzer, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035 003, Porto Alegre, RS, Brazil. (Email [email protected])
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Abstract

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Keywords

dehydroepiandrosteronefollicular developmenthyperandrogenismPCOSrat ovary
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 7 , Issue 4 , August 2016 , pp. 384 - 390
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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References

1. Palma, GA, Argañaraz, ME, Barrera, AD, et al. Biology and biotechnology of follicle development. ScientificWorldJournal. 2012; 2012, 938138.Google Scholar
2. Prizant, H, Gleicher, N, Sen, A. Androgen actions in the ovary: balance is key. J Endocrinol. 2014; 222, R141–R151.Google Scholar
3. Sen, A, Prizant, H, Light, A, et al. Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proc Natl Acad Sci U S A. 2014; 111, 3008–3013.Google Scholar
4. Spritzer, PM. Polycystic ovary syndrome: reviewing diagnosis and management of metabolic disturbances. Arq Bras Endocrinol Metabol. 2014; 58, 182–187.Google Scholar
5. Franks, S, McCarthy, MI, Hardy, K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl. 2006; 29, 278–284.CrossRefGoogle ScholarPubMed
6. Sir-Petermann, T, Codner, E, Maliqueo, M, et al. Increased anti-Müllerian hormone serum concentrations in prepubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006; 91, 3105–3109.Google Scholar
7. Sir-Petermann, T, Codner, E, Pérez, V, et al. Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2009; 941, 1923–1930.Google Scholar
8. Abbott, DH, Dumesic, DA, Franks, S. Developmental origin of polycystic ovary syndrome – a hypothesis. J Endocrinol. 2002; 174, 1–5.Google Scholar
9. Dumesic, DA, Padmanabhan, V, Abbott, DH. Polycystic ovary syndrome and oocyte developmental competence. Obstet Gynecol Surv. 2008; 63, 39–48.Google Scholar
10. Franks, S, Stark, J, Hardy, K. Follicle dynamics and anovulation in polycystic ovary syndrome. Hum Reprod Update. 2008; 14, 367–378.Google Scholar
11. Pasquali, R, Stener-Victorin, E, Yildiz, BO, et al. PCOS Forum: research in polycystic ovary syndrome today and tomorrow. Clin Endocrinol (Oxf). 2011; 74, 424–433.Google Scholar
12. Franks, S. Animal models and the developmental origins of polycystic ovary syndrome: increasing evidence for the role of androgens in programming reproductive and metabolic dysfunction. Endocrinology. 2012; 153, 2536–2538.Google Scholar
13. Orisaka, M, Tajima, K, Tsang, BK, Kotsuji, F. Oocyte-granulosa-theca cell interactions during preantral follicular development. J Ovarian Res. 2009; 2, 9.CrossRefGoogle ScholarPubMed
14. Gervásio, CG, Bernuci, MP, Silva-de-Sá, MF, Rosa-E-Silva, AC. The role of androgen hormones in early follicular development. ISRN Obstet Gynecol. 2014; 2014, 818010.Google Scholar
15. Loughlin, T, Cunningham, S, Moore, A, et al. Adrenal abnormalities in polycystic ovary syndrome. J Clin Endocrinol Metab. 1986; 62, 142–147.Google Scholar
16. Apter, D, Bützow, T, Laughlin, GA, Yen, SS. Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome. J Clin Endocrinol Metab. 1994; 79, 119–125.Google Scholar
17. Lee, MT, Anderson, E, Lee, GY. Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone. Anat Rec. 1991; 231, 185–192.CrossRefGoogle ScholarPubMed
18. Anderson, E, Lee, MT, Lee, GY. Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone. Anat Rec. 1992; 234, 359–382.Google Scholar
19. Sander, V, Solano, ME, Elia, E, et al. The influence of dehydroepiandrosterone on early pregnancy in mice. Neuroimmunomodulation. 2005; 12, 285–292.CrossRefGoogle ScholarPubMed
20. Sander, V, Luchetti, CG, Solano, ME, et al. Role of the N, N’-dimethylbiguanide metformin in the treatment of female prepuberal BALB/c mice hyperandrogenized with dehydroepiandrosterone. Reproduction. 2006; 131, 591–602.Google Scholar
21. Henmi, H, Endo, T, Nagasawa, K, et al. Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. Biol Reprod. 2001; 64, 157–162.Google Scholar
22. Faut, M, Elia, EM, Parborell, F, et al. Peroxisome proliferator-activated receptor gamma and early folliculogenesis during an acute hyperandrogenism condition. 2011; 95, 333–337.Google Scholar
23. Gal, M, Orly, J. Ketoconazole inhibits ovulation as a result of arrest of follicular steroidogenesis in the rat ovary. Clin Med Insights Reprod Health. 2014; 8, 37–44.CrossRefGoogle ScholarPubMed
24. Velez, LM, Heber, MF, Ferreira, SR, et al. Effect of hyperandrogenism on ovarian function. Reproduction. 2015; 149, 577–585.CrossRefGoogle ScholarPubMed
25. Parborell, F, Pecci, A, Gonzalez, O, Vitale, A, Tesone, M. Effects of a gonadotropin-releasing hormone agonist on rat ovarian follicle apoptosis: regulation by epidermal growth factor and the expression of Bcl-2-related genes. Biol Reprod. 2002; 67, 481–4866.CrossRefGoogle ScholarPubMed
26. Practice Committee of American Society for Reproductive Medicine. Gonadotropin preparations: past, present, and future perspectives. Fertil Steril. 2008; 90, S13–S20.CrossRefGoogle Scholar
27. Pedersen, T, Peters, H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil. 1968; 17, 555–557.Google Scholar
28. Cruz, G, Barra, R, González, D, Sotomayor-Zárate, R, Lara, HE. Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats. Fertil Steril. 2012; 98, 1283–1290.CrossRefGoogle ScholarPubMed
29. Elia, E, Sander, V, Luchetti, CG, et al. The mechanisms involved in the action of metformin in regulating ovarian function in hyperandrogenized mice. Mol Hum Reprod. 2006; 12, 475–481.Google Scholar
30. Misugi, T, Ozaki, K, El Beltagy, K, et al. Insulin-lowering agents inhibit synthesis of testosterone in ovaries of DHEA-induced PCOS rats. Gynecol Obstet Invest. 2006; 61, 208–215.Google Scholar
31. Okutsu, Y, Itoh, MT, Takahashi, N, Ishizuka, B. Exogenous androstenedione induces formation of follicular cysts and premature luteinization of granulosa cells in the ovary. Fertil Steril. 2010; 93, 927–935.Google Scholar
32. Tarumi, W, Tsukamoto, S, Okutsu, Y, et al. Androstenedione induces abnormalities in morphology and function of developing oocytes, which impairs oocyte meiotic competence. Fertil Steril. 2012; 97, 469–476.CrossRefGoogle ScholarPubMed
33. Walters, KA, Allan, CM, Handelsman, DJ. Rodent models for human polycystic ovary syndrome. Biol Reprod. 2012; 86, 149.CrossRefGoogle ScholarPubMed
34. Wu, XY, Li, ZL, Wu, CY, et al. Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague-Dawley rats. Endocr J. 2010; 57, 201–209.Google Scholar
35. Zhou, Y, Kang, J, Chen, D, Han, N, Ma, H. Ample evidence: dehydroepiandrosterone (DHEA) conversion into activated steroid hormones occurs in adrenal and ovary in female rat. PLoS One. 2015; 10, e0124511.CrossRefGoogle ScholarPubMed
36. Lenie, S, Smitz, J. Functional AR signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biol Reprod. 2009; 80, 685–695.CrossRefGoogle Scholar
37. Collado-Fernandez, E, Picton, HM, Dumollard, R. Metabolism throughout follicle and oocyte development in mammals. Int J Dev Biol. 2012; 56, 799–808.Google Scholar
38. Vendola, K, Zhou, J, Wang, J, Bondy, CA. Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod. 1999; 14, 2328–2332.Google Scholar
39. Vendola, K, Zhou, J, Wang, J, et al. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Biol Reprod. 1999; 61, 353–357.Google Scholar
40. Weil, S, Vendola, K, Zhou, J, Bondy, CA. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab. 1999; 84, 2951–2956.Google Scholar
41. Lebbe, M, Woodruff, TK. Involvement of androgens in ovarian health and disease. Mol Hum Reprod. 2013; 19, 828–837.Google Scholar