Email this article Dynamics of blood adipokine levels and their ratios in assisted reproductive technology programs depending on the clinical pregnancy onset
- Authors: Ryzhov J.R.1, Makhmadalieva M.R.1, Lesik E.A.1, Komarova E.M.1, Ishchuk M.A.1, Tapilskaya N.I.1, Gzgzyan A.M.1, Bespalova O.N.1
-
Affiliations:
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Issue: Vol 73, No 5 (2024)
- Pages: 84-95
- Section: Original study articles
- Submitted: 22.05.2024
- Accepted: 18.09.2024
- Published: 04.12.2024
- URL: https://journals.eco-vector.com/jowd/article/view/632177
- DOI: https://doi.org/10.17816/JOWD632177
- ID: 632177
Cite item
Open Access
Access granted
Abstract
BACKGROUND: The adipokines leptin, adiponectin, and ghrelin are expressed not only in adipose tissue but also in the hypothalamic-pituitary-gonadal axis organs and the uterus. They regulate the gonadotropin-releasing hormone and gonadotropin secretion, steroidogenesis, folliculogenesis, and implantation, and serve as promising markers of assisted reproductive technology program outcomes.
AIM: The aim of this study was to evaluate the dynamics of blood adipokine levels and their ratios during the controlled ovarian hyperstimulation in assisted reproductive technology programs depending on the onset of clinical pregnancy.
MATERIALS AND METHODS: This study involved 51 patients undergoing infertility treatment using assisted reproductive technology in a short protocol with gonadotropin-releasing hormone antagonists. Depending on the onset of clinical pregnancy, two study groups were formed: non-pregnant (group 1, n = 22) and pregnant (group 2, n = 29). Blood leptin, adiponectin, and ghrelin levels were assessed using enzyme immunoassay at three points: assisted reproductive technology protocol start-up, the day of oocyte pick-up, and the day of embryo transfer.
RESULTS: On the day of oocyte pick-up, patients in group 1 had higher leptin levels (5.47 ± 1.92 vs. 3.76 ± 0.75 ng/ml; p = 0.0004), leptin/adiponectin ratios (11.45 ± 4.50 vs. 4.73 ± 1.08; p < 0.001), and leptin/ghrelin ratios (0.43 ± 0.17 vs. 0.24 ± 0.07; p < 0.001). On the day of embryo transfer, patients in group 1 had higher levels of leptin (6.37 ± 2.13 vs. 3.29 ± 1.21 ng/ml; p < 0.001) and adiponectin (0.75 ± 0.22 vs. 0.60 ± 0.09 ng/ml; p = 0.001), as well as ratios of leptin/adiponectin (9.06 ± 3.73 vs. 5.59 ± 2.32; p < 0.001), leptin/ghrelin (0.48 ± 0.15 vs. 0.20 ± 0.07; p < 0.001), and adiponectin/ghrelin (0.06 ± 0.02 vs. 0.04 ± 0.01; p < 0.001).
CONCLUSIONS: The data obtained indicate that blood adipokine levels change during the controlled ovarian hyperstimulation in assisted reproductive technology protocols depending on clinical pregnancy and can be used to predict its onset.
Full Text
About the authors
Julian R. Ryzhov
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Author for correspondence.
Email: julian.ryzhov@gmail.com
ORCID iD: 0000-0002-5073-8279
SPIN-code: 8320-1234
MD
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Manizha R. Makhmadalieva
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: 2563737@mail.ru
ORCID iD: 0000-0002-9578-8931
SPIN-code: 1523-0196
MD
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Elena A. Lesik
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: lesike@yandex.ru
ORCID iD: 0000-0003-1611-6318
SPIN-code: 6102-4690
Cand. Sci. (Biology)
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Evgeniia M. Komarova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: evgmkomarova@gmail.com
ORCID iD: 0000-0002-9988-9879
SPIN-code: 1056-7821
Cand. Sci. (Biology)
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Mariia A. Ishchuk
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: mashamazilina@gmail.com
ORCID iD: 0000-0002-4443-4287
SPIN-code: 1237-6373
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034
Natalia I. Tapilskaya
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: tapnatalia@yandex.ru
ORCID iD: 0000-0001-5309-0087
SPIN-code: 3605-0413
MD, Dr. Sci. (Medicine), Professor
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Alexander M. Gzgzyan
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: agzgzyan@gmail.com
ORCID iD: 0000-0003-3917-9493
SPIN-code: 6412-4801
MD, Dr. Sci. (Medicine), Professor
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Olesya N. Bespalova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089
MD, Dr. Sci. (Medicine)
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034References
- Taylor EB. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci (Lond). 2021;135(6):731–752. doi: 10.1042/CS20200895
- Pérez-Pérez A, Sánchez-Jiménez F, Maymó J, et al. Role of leptin in female reproduction. Clin Chem Lab Med. 2015;53(1):15–28. doi: 10.1515/cclm-2014-0387
- Shpakov AO, Ryzhov JR, Bakhtyukov AA, et al. The regulation of the male hypothalamic-pituitary-gonadal axis and testosterone production by adipokines. In: Estrada M., editor. Advances in testosterone action. Croatia: Intech Open Access Publisher; 2018. doi: 10.5772/intechopen.76321
- Knerr I, Herzog D, Rauh M, et al. Leptin and ghrelin expression in adipose tissues and serum levels in gastric banding patients. Eur J Clin Invest. 2006:36(6):389–394. doi: 10.1111/j.1365-2362.2006.01642.x
- Oliveira BSP, Costa JAS, Gomes ET, et al. Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in goat ovary and its effect on oocyte nuclear maturation in vitro. Theriogenology. 2017;104:127–133. doi: 10.1016/j.theriogenology.2017.08.013
- Shpakov АО. Adipokines and their role in the regulation of reproductive functions. Saint-Petersburg: Politech-Press; 2018. EDN: ZUWFQD (In Russ.)
- Bakhtyukov AA, Lebedev IA, Kuznetsova VS, et al. Leptin fragment 116–122 modulates testicular steroidogenesis in male rats. J Evol Biochem Physiol. 2023;59(3):904–913. doi: 10.1134/S0022093023030225
- Craig J, Zhu H, Dyce PW, et al. Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway. Endocrinology. 2004;145(11):5355–5363. doi: 10.1210/en.2004-0783
- Sirini MA, Anchordoquy JM, Anchordoquy JP, et al. The presence of acylated ghrelin during in vitro maturation of bovine oocytes induces cumulus cell DNA damage and apoptosis, and impairs early embryo development. Zygote. 2017;25(5):601–611. doi: 10.1017/S0967199417000478
- González RR, Caballero-Campo P, Jasper M, et al. Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab. 2000;85(12):4883–4888. doi: 10.1210/jcem.85.12.7060
- Luque EM, Díaz-Luján CM, Paira DA, et al. Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress. Front Endocrinol (Lausanne). 2023;14. doi: 10.3389/fendo.2023.1288779
- Duval F, Dos Santos E, Moindjie H, et al. Adiponectin limits differentiation and trophoblast invasion in human endometrial cells. J Mol Endocrinol. 2017;59(3):285–297. doi: 10.1530/JME-17-0046
- Ryzhov JR, Shpakov AO, Tkachenko NN, et al. The follicular levels of adipokines and their ratio as the prognostic markers of in vitro fertilization outcomes. Gynecol Endocrinol. 2021;37(Suppl 1):31–34. doi: 10.1080/09513590.2021.2006512
- Dupont J, Pollet-Villard X, Reverchon M, et al. Adipokines in human reproduction. Horm Mol Biol Clin Investig. 2015;24(1):11–24. doi: 10.1515/hmbci-2015-0034
- Casabiell X, Piñeiro V, Peino R, et al. Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men. J Clin Endocrinol Metab. 1998;83(6):2149–2155. doi: 10.1210/jcem.83.6.4849
- Geber S, Brandão AH, Sampaio M. Effects of estradiol and FSH on leptin levels in women with suppressed pituitary. Reprod Biol Endocrinol. 2012;10:45. doi: 10.1186/1477-7827-10-45
- Capllonch-Amer G, Lladó I, Proenza AM, et al. Opposite effects of 17-β estradiol and testosterone on mitochondrial biogenesis and adiponectin synthesis in white adipocytes. J Mol Endocrinol. 2014;52(2):203–214. doi: 10.1530/JME-13-0201
- Tvarijonaviciute A, Carrillo-Sanchez JD, Ceron JJ. Effect of estradiol and progesterone on metabolic biomarkers in healthy bitches. Reprod Domest Anim. 2013;48(3):520–524. doi: 10.1111/rda.12120
- Dafopoulos K, Chalvatzas N, Kosmas G, et al. The effect of estrogens on plasma ghrelin concentrations in women. J Endocrinol Invest. 2010;33(2):109–112. doi: 10.1007/BF03346563
- Eliasson B, Smith U. Leptin levels in smokers and long-term users of nicotine gum. Eur J Clin Invest. 1999;29(2):145–152. doi: 10.1046/j.1365-2362.1999.00420.x
- Nikolettos K, Nikolettos N, Vlahos N, et al. Role of leptin, adiponectin, and kisspeptin in polycystic ovarian syndrome pathogenesis. Minerva Obstet Gynecol. 2023;75(5):460–467. doi: 10.23736/S2724-606X.22.05139-9
- Weigle DS, Breen PA, Matthys CC, et al. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005;82(1):41–48. doi: 10.1093/ajcn.82.1.41
- Dardzińska JA, Małgorzewicz S, Kaska Ł, et al. Fasting and postprandial acyl and desacyl ghrelin levels in obese and non-obese subjects. Endokrynol Pol. 2014;65(5):377–381. doi: 10.5603/EP.2014.0052
- Akarsu S, Buke B, Göde F, et al. Association of serum and follicular fluid leptin and ghrelin levels with in vitro fertilization success. Ginekol Pol. 2017;88(9):469–474. doi: 10.5603/gp.a2017.0086
- Anifandis G, Koutselini E, Louridas K, et al. Estradiol and leptin as conditional prognostic IVF markers. Reproduction. 2005;129(4):531–534. doi: 10.1530/rep.1.00567
- Hill MJ, Uyehara CF, Hashiro GM, et al. The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle. J Assist Reprod Genet. 2007;24(5):183–188. doi: 10.1007/s10815-007-9106-0
- Mantzoros CS, Cramer DW, Liberman RF, et al. Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome. Hum Reprod. 2000;15(3):539–544. doi: 10.1093/humrep/15.3.539
- Heldsinger A, Grabauskas G, Wu X, et al. Ghrelin induces leptin resistance by activation of suppressor of cytokine signaling 3 expression in male rats: implications in satiety regulation. Endocrinology. 2014;155(10):3956–3969. doi: 10.1210/en.2013-2095
- Lu CW, Yang KC, Chi YC, et al. Adiponectin-leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance. Ann Med. 2023;55(1):634–642. doi: 10.1080/07853890.2023.2179106
- Di Filippo L, De Lorenzo R, Sciorati C, et al. Adiponectin to leptin ratio reflects inflammatory burden and survival in COVID-19. Diabetes Metab. 2021;47(6):101268. doi: 10.1016/j.diabet.2021.101268
Supplementary files
