Association of clinical, laboratory, and morphological characteristics of the ovaries in girls with Turner Syndrome and spontaneous puberty

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Objective: To present the characteristics of the ovarian reserve in girls with Turner syndrome based on morphological, clinical, laboratory, and instrumental parameters.

Materials and methods: A comparative morphological, morphometric, and immunohistochemical study of the ovarian cortex fragments was conducted in 20 girls. This group included 10 patients with Turner syndrome and spontaneous puberty, who exhibited no clinical or laboratory signs of premature ovarian insufficiency, and 10 girls with paraovarian cysts. The study examined the relationship between the morphological characteristics of the obtained samples and the stage of sexual development according to Tanner, ultrasound parameters of the ovaries, results of cytogenetic studies of blood lymphocytes, and hormonal status of girls with Turner syndrome.

Results: All girls with paraovarian cysts and 9 of 10 patients with Turner syndrome had follicles in the ovarian cortex, and abnormal morphology was observed in all girls with Turner syndrome and 80% in the control group. All follicles from patients with Turner syndrome expressed the oocyte-specific immunohistochemical markers ZP2, GDF9, BMP15, and CD117. Follicle density in Turner syndrome was 6.8 times lower than that in the control group and did not correlate with age, stage of puberty according to the Tanner scale, serum levels of FSH, LH, estradiol, AMH, inhibin B, testosterone, antral follicle count, or ovarian volume. However, this was associated with the presence of a 46,XX, or 47,XXX cell clone in the karyotype. Healthy follicles in the ovarian cortex were not detected in girls with Turner syndrome who had FSH and AMH levels > 15 IU/l and < 0.307 ng/ml, respectively. Among patients with X-chromosome mosaicism without structural anomalies, a positive correlation was found between follicle density and inhibin B level in the blood.

Conclusion: The prospects for performing the ovarian cortex cryopreservation procedure in girls with Turner syndrome may be determined by the combined presence of X-chromosome mosaicism without structural abnormalities, normal serum FSH levels for the corresponding age, inhibin B levels appropriate for the stage of sexual development according to Tanner, and detectable AMH levels.

全文:

受限制的访问

作者简介

Anna Turchinets

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

编辑信件的主要联系方式.
Email: Ponomarevaanna28@gmail.com
ORCID iD: 0000-0002-4478-9133

PhD student, Physician at the Department of Pediatric and Adolescent Gynecology

俄罗斯联邦, Moscow

Alina Badlaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alinamagnaeva03@gmail.com
ORCID iD: 0000-0001-5223-9767

PhD, Senior Researcher at the 1st Pathology Department, Physician at the 1st Pathology Department

俄罗斯联邦, Moscow

Elena Uvarovа

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: elena-uvarova@yandex.ru
ORCID iD: 0000-0002-3105-5640

Corresponding Member of the Russian Academy of Sciences, Dr. Med. Sci., Professor at the Department of Obstetrics, Gynecology and Perinatology, Head of the Department of Pediatric and Adolescent Gynecology

俄罗斯联邦, Moscow; Moscow

Aleksandra Asaturova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_asaturova@oparina4.ru
ORCID iD: 0000-0001-8739-5209

Dr. Med. Sci., Head of the 1st Pathology Department

俄罗斯联邦, Moscow

Nail Kamaletdinov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: sunsh86@mail.ru

Embryologist at the 1st Gynecological Department

俄罗斯联邦, Moscow

Irina Kiseleva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kiseleva_i@oparina4.ru

PhD, Clinical Care Supervisor at the Department of Pediatric and Adolescent Gynecology

俄罗斯联邦, Moscow

Zaira Kumykova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: zai-kumykova@yandex.ru
ORCID iD: 0000-0001-7511-1432

PhD, Senior Researcher at the Department of Pediatric and Adolescent Gynecology

俄罗斯联邦, Moscow

Alla Gavisova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: gavialla@yandex.ru

Dr. Med. Sci., Head of the 1st Gynecological Department

俄罗斯联邦, Moscow

参考

  1. Dowlut-McElroy T., Shankar R.K. The care of adolescents and young adults with Turner syndrome: a pediatric and adolescent gynecology perspective. J. Pediatr. Adolesc. Gynecol. 2022; 35(4): 429-34. https://dx.doi.org/10.1016/ j.jpag.2022.02.002
  2. Webber L., Davies M., Anderson R., Bartlett J., Braat D., Cartwright B. et al.; European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum. Reprod. 2016; 31(5): 926-37. https://dx.doi.org/10.1093/humrep/dew027
  3. Lunding S.A., Aksglaede L., Anderson R.A., Main K.M., Juul A., Hagen C.P. et al. AMH as predictor of premature ovarian insufficiency: a longitudinal study of 120 Turner syndrome patients. J. Clin. Endocrinol. Metab. 2015; 100(7): E1030-8. https://dx.doi.org/10.1210/jc.2015-1621
  4. Fitz V.W., Law J.R., Peavey M. Characterizing ovarian function by karyotype in a cohort of women with Turner’s syndrome. Fertil. Steril. 2019; 111(4): e27-e28. https://dx.doi.org/10.1016/j.fertnstert.2019.02.074
  5. Reynaud K., Cortvrindt R., Verlinde F., De Schepper J., Bourgain C., Smitz J. Number of ovarian follicles in human fetuses with the 45,X karyotype. Fertil. Steril. 2004; 81(4): 1112-9. https://dx.doi.org/10.1016/j.fertnstert.2003.12.011
  6. Hook E.B., Warburton D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss. Hum. Genet. 2014; 133(4): 417-24. https://dx.doi.org/10.1007/s00439-014-1420-x
  7. Burgoyne P.S., Baker T.G. Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women. J. Reprod. Fertil. 1985; 75(2): 633-45. https://dx.doi.org/10.1530/jrf.0.0750633
  8. Modi D.N., Sane S., Bhartiya D. Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Mol. Hum. Reprod. 2003; 9(4): 219-25. https://dx.doi.org/10.1093/molehr/gag031
  9. Mercer C.L., Lachlan K., Karcanias A., Affara N., Huang S., Jacobs P.A. et al. Detailed clinical and molecular study of 20 females with Xq deletions with special reference to menstruation and fertility. Eur. J. Med. Genet. 2013; 56(1): 1-6. https://dx.doi.org/10.1016/j.ejmg.2012.08.012
  10. Persani L., Rossetti R., Cacciatore C., Bonomi M. Primary ovarian insufficiency: X chromosome defects and autoimmunity. J. Autoimmun. 2009; 33(1): 35-41. https://dx.doi.org/10.1016/j.jaut.2009.03.004
  11. Fukami M. Ovarian dysfunction in women with Turner syndrome. Front. Endocrinol. (Lausanne). 2023; 14: 1160258. https://dx.doi.org/10.3389/fendo.2023.1160258
  12. Persani L., Rossetti R., Di Pasquale E., Cacciatore C., Fabre S. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Hum. Reprod. Update. 2014; 20(6): 869-83. https://dx.doi.org/10.1093/humupd/dmu036
  13. San Roman A.K., Page D.C. A strategic research alliance: Turner syndrome and sex differences. Am. J. Med. Genet. C Semin. Med. Genet. 2019; 181(1): 59-67. https://dx.doi.org/10.1002/ajmg.c.31677
  14. Nadesapillai S., van der Velden J., Smeets D., van de Zande G., Braat D., Fleischer K. et al. Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary. Fertil. Steril. 2021; 115(5): 1280-7. https://dx.doi.org/10.1016/ j.fertnstert.2020.11.006
  15. Hreinsson J.G., Otala M., Fridström M., Borgström B., Rasmussen C., Lundqvist M. et al. Follicles are found in the ovaries of adolescent girls with Turner syndrome. J. Clin. Endocrinol. Metab. 2002; 87(8): 3618-23. https://dx.doi.org/10.1210/jcem.87.8.8753
  16. Mamsen L.S., Charkiewicz K., Anderson R.A., Telfer E.E., McLaughlin M., Kelsey T.W. et al. Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation. Fertil. Steril. 2019; 111(6): 1217-1225.e3. https://dx.doi.org/10.1016/ j.fertnstert.2019.02.003
  17. Bernard V., Donadille B., Zenaty D., Courtillot C., Salenave S., Brac de la Perrière A. et al. CMERC Center for Rare Disease. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum. Reprod. 2016; 31(4): 782-8. https://dx.doi.org/10.1093/humrep/dew012
  18. Gravholt C.H., Andersen N.H., Christin-Maitre S., Davis S.M., Duijnhouwer A., Gawlik A. et al.; International Turner Syndrome Consensus Group; Backeljauw P.F. Clinical practice guidelines for the care of girls and women with Turner syndrome. Eur. J. Endocrinol. 2024; 190(6): G53-G151. https://dx.doi.org/10.1093/ejendo/lvae050
  19. Schmidt K.L., Byskov A.G., Nyboe Andersen A., Müller J., Yding Andersen C. Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Hum. Reprod. 2003; 18(6): 1158-64. https://dx.doi.org/10.1093/humrep/deg246
  20. Hassan J., Knuus K., Lahtinen A., Rooda I., Otala M., Tuuri T. et al. Reference standards for follicular density in ovarian cortex from birth to sexual maturity. Reprod. Biomed. Online. 2023; 47(4): 103287. https://dx.doi.org/10.1016/ j.rbmo.2023.103287
  21. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr. Rev. 1996; 17(2): 121-55. https://dx.doi.org/10.1210/edrv-17-2-121
  22. Pangas S.A., Choi Y., Ballow D.J., Zhao Y., Westphal H., Matzuk M.M. et al. Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc. Natl. Acad. Sci. U. S. A. 2006; 103(21): 8090-5. https:// dx.doi.org/10.1073/pnas.0601083103
  23. Gook D.A., Edgar D.H., Borg J., Martic M. Detection of zona pellucida proteins during human folliculogenesis. Hum. Reprod. 2008; 23(2): 394-402. https://dx.doi.org/10.1093/humrep/dem373
  24. Rankin T.L., O'Brien M., Lee E., Wigglesworth K., Eppig J., Dean J. Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development. Development. 2001; 128(7): 1119-26. https://dx.doi.org/10.1242/dev.128.7.1119
  25. Park M.J., Ahn J.W., Kim K.H., Bang J., Kim S.C., Jeong J.Y. et al. Prediction of ovarian aging using ovarian expression of BMP15, GDF9, and C-KIT. Exp. Biol. Med. (Maywood). 2020; 245(8): 711-9. https:// dx.doi.org/10.1177/1535370220915826
  26. Belli M., Shimasaki S. Molecular aspects and clinical relevance of GDF9 and BMP15 in ovarian function. Vitam. Horm. 2018; 107: 317-48. https:// dx.doi.org/10.1016/bs.vh.2017.12.003
  27. Driancourt M.A., Reynaud K., Cortvrindt R., Smitz J. Roles of KIT and KIT LIGAND in ovarian function. Rev. Reprod. 2000; 5(3): 143-52. https://dx.doi.org/10.1530/ror.0.0050143
  28. Remmele W., Stegner H.E. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987; 8: 138-40.
  29. Dolmans M.M., Donnez J., Camboni A., Demylle D., Amorim C., Van Langendonckt A. et al. IVF outcome in patients with orthotopically transplanted ovarian tissue. Hum Reprod. 2009; 24(11): 2778-87. https://dx.doi.org/10.1093/humrep/dep289
  30. Schleedoorn M.J., Fleischer K., Braat D., Oerlemans A., van der Velden A., Peek R. Why Turner patients with 45, X monosomy should not be excluded from fertility preservation services. Reprod. Biol. Endocrinol. 2022; 20(1): 143. https://dx.doi.org/10.1186/s12958-022-01015-z
  31. Nadesapillai S., van der Velden J., van der Coelen S., Schleedoorn M., Sedney A., Spath M. et al. TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study. Fertil. Steril. 2023; 120(5): 1048-60. https://dx.doi.org/10.1016/ j.fertnstert.2023.08.004
  32. Jeve Y.B., Gelbaya T., Fatum M. Time to consider ovarian tissue cryopreservation for girls with Turner's syndrome: an opinion paper. Hum. Reprod. Open. 2019; 2019(3): hoz016. https://dx.doi.org/10.1093/hropen/hoz016
  33. Bayne R.A., Kinnell H.L., Coutts S.M., He J., Childs A.J., Anderson R.A. GDF9 is transiently expressed in oocytes before follicle formation in the human fetal ovary and is regulated by a novel NOBOX transcript. PLoS One. 2015; 10(3): e0119819. https://dx.doi.org/10.1371/journal.pone.0119819
  34. Gilchrist R.B., Lane M., Thompson J.G. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum. Reprod. Update. 2008; 14(2): 159-77. https://dx.doi.org/10.1093/humupd/dmm040
  35. Wei L.N., Huang R., Li L.L., Fang C., Li Y., Liang X.Y. Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome. J. Assist. Reprod. Genet. 2014; 31(11): 1483-90. https://dx.doi.org/10.1007/s10815-014-0319-8
  36. Sehested A., Juul A.A., Andersson A.M., Petersen J.H., Jensen T.K., Müller J. et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. J. Clin. Endocrinol. Metab. 2000; 85(4): 1634-40. https://dx.doi.org/10.1210/jcem.85.4.6512
  37. Wen J., Huang K., Du X., Zhang H., Ding T., Zhang C. et al. Can inhibin B reflect ovarian reserve of healthy reproductive age women effectively? Front. Endocrinol. (Lausanne). 2021; 12: 626534. https://dx.doi.org/10.3389/fendo.2021.626534
  38. Borelli-Kjær A., Aksglaede L., Jensen R.B., Hagen C.P., Ljubicic M.L., Busch A.S. et al. Serum concentrations of inhibin B in healthy females and males throughout life. J. Clin. Endocrinol. Metab. 2024; 110(1): 70-7. https://dx.doi.org/10.1210/clinem/dgae439

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Correlation of PF in girls with CT and the comparison group

下载 (125KB)
索引源数据
3. 2. Morphological changes in the follicles of girls with C and the comparison group (hematoxylin and eosin staining, x400). A - primary (black arrow) and primordial follicles (blue arrow) with an incomplete layer of granulosa cells; B - absence of oocytes in the follicles (black arrow); C - oocytes with pale nuclei with indistinct contours (black arrow), wrinkling of the ooplasm (blue arrow); D - partial absence of connection of the oocyte with the basement membrane (black arrow); D - dioecytic follicle (black arrow)

下载 (1000KB)
索引源数据
4. 3. Degenerative changes in the follicles of girls with C (hematoxylin and eosin staining, x400). A is a degenerating primordial follicle with oocyte karyopycnosis (black arrow); B - degenerating primordial follicle with karyopycnosis of granulosa cells; C - atresied follicle with karyopycnosis of the oocyte (black arrow) and karyopycnosis of granulosa cells (blue arrow)

下载 (365KB)
索引源数据
5. Fig. 4. IHC-reaction with antibodies in fragments of the cortical layer of the ovaries. A - moderate staining of the ooplasm of primordial follicles with an antibody to ZP2 in a patient of the comparison group (xZOO); B - pronounced staining of the ooplasm of primordial follicles with an antibody to ZP2 in a patient with CT; C - weak staining of the ooplasm of primordial follicles with an antibody KV1'1P15 in a patient with ।1:t (XZOO); D - pronounced staining of the oolemma of primordial follicles follicles with an antibody to CD117 in patient gG 1 of the upp comparison Ix200);D-,> measured staining of the ooplasm of primordial follicles and antibody granulosa cells. c>MKGDF9ynauHei ■1TKIST(:<400); E - marked staining of the ooplasm of the primordial follicles antibody"l to GDF9 in a patient of the comparison group (x400)

下载 (1MB)
索引源数据
6. Fig. 5. Correlation of AMH and inhibin B levels with PF depending on the karyotype of patients with CT 6-| 200- 150- From “ 100- s 50-

下载 (100KB)
索引源数据

版权所有 © Bionika Media, 2025