ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet12825ometendo-12825Research ArticleОБЗОРЫREVIEWSРоль адипокинов и грелина в регуляции овариальной функции при ожиренииAdipokinesand Ghrelin Rolein Regulation of Ovarian Function in Obesityhttps://orcid.org/0000-0002-3600-990XАбдусаламоваА. И.AbdusalamovaA. I.

Абдусаламова Альбина Исламовна, клинический ординатор кафедры акушерства и гинекологии 

Санкт-Петербург

Albina I. Abdusalamova, MD

Saint Petersburg

abdusalamova.albina2016@gmail.comhttps://orcid.org/0000-0002-1161-1558БеттихерО. А.BettikherO. A.

Беттихер Офелия Андреевна, кандидат медицинских наук , ассистент кафедры акушерства и гинекологии, научный сотрудник НИЛ репродукции и здоровья женщины; научный сотрудник отдела акушерства и перинатологии 

197341, Санкт-Петербург, улица Аккуратова, д 2Б

ResearcherID: AAH-8832-2020;

Scopus Author ID: 57190122861;

eLibrary SPIN: 4398-3964

Ofelia A. Bettikher, MD, PhD

2В Akkuratova street, 197341, Saint Petersburg

Researcher ID: AAH-8832-2020;

Scopus Author ID: 57190122861;

eLibrary SPIN: 4398-3964

ophelia.bettikher@gmail.comhttps://orcid.org/0000-0001-8498-7938РуденкоК. А.RudenkoK. A.

Руденко Ксения Александровна, аспирант 

Санкт-Петербург

ResearcherID: ABC-1438-2021;

eLibrary SPIN: 3534-4785

Kseniia A. Rudenko, postgraduate student

Saint Petersburg

Researcher ID: ABC-1438-2021;

eLibrary SPIN: 3534-4785

xeniaruru@yandex.ruhttps://orcid.org/0000-0002-6970-7085БеляеваО. А.BelyaevaO. A.

Беляева Ольга Андреевна, клинический ординатор кафедры акушерства и гинекологии 

Санкт-Петербург

Olga A. Belyaeva, MD

Saint Petersburg

belyaevaolga0138@gmail.comhttps://orcid.org/0000-0003-4925-0126НеймаркА. Е.NeimarkA. E.

Неймарк Александр Евгеньевич, кандидат медицинских наук 

Санкт-Петербург

ResearcherID: AAT-9752-2021;

Scopus Author ID: 56651924200;

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Aleksandr E. Neimark, MD, PhD

Saint Petersburg

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sas_spb@mail.ruhttps://orcid.org/0000-0003-4431-3917ЗазерскаяИ. Е.ZazerskayaI. E.

Зазерская Ирина Евгеньевна, доктор медицинских наук, профессор 

Санкт-Петербург

ResearcherID: AAI-1309-2020;

Scopus Author ID: 55981393900

;eLibrary SPIN: 5683-6741

Irina E. Zazerskaya, MD, PhD, Professor

Saint Petersburg

Researcher ID: AAI-1309-2020;

Scopus Author ID: 55981393900;

еLibrary SPIN: 5683-6741

zazera@mail.ruНациональный медицинский исследовательский центр им. В.А. АлмазоваРоссияAlmazov National Medical Research CentreRussian FederationНациональный медицинский исследовательский центр им. В.А. Алмазова; Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. ОттаРоссияAlmazov National Medical Research Centre; The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. OttRussian Federation202229082022193324331Copyright © Абдусаламова А.И., Беттихер О.А., Руденко К.А., Беляева О.А., Неймарк А.Е., Зазерская И.Е., 20232023Абдусаламова А.И., Беттихер О.А., Руденко К.А., Беляева О.А., Неймарк А.Е., Зазерская И.Е.Abdusalamova A.I., Bettikher O.A., Rudenko K.A., Belyaeva O.A., Neimark A.E., Zazerskaya I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/12825

В мире наблюдается резкая тенденция к росту заболеваемости ожирением, которая с каждым годом набирает обороты среди всех групп населения, в том числе среди женщин репродуктивного возраста. Учитывая внушительный перечень ассоциированных с ожирением заболеваний, а также отрицательную обратную корреляцию степени выраженности ожирения с фертильностью, данная проблема приобретает глобальный характер не только в социальной сфере, но также является демографически значимой.

Наряду с прочими патогенетическими механизмами, приводящими к стойкой ановуляции, дисбаланс продукции адипокинов жировой тканью также может служить одним из важных звеньев в развитии репродуктивной дисфункции. Несмотря на значимый интерес к данной теме, большое количество открытых ранее адипокинов все еще не изучено. Среди адипокинов наиболее известны эффекты адипонектина и лептина на репродуктивную функцию. Изменение уровней адипонектина и лептина может влиять на гипоталамо-гипофизарно-гонадную сигнализацию, фолликулогенез, оогенез и стероидогенез. Лептин к тому же участвует в инициации полового созревания, регуляции менструального цикла, изменяет баланс между пролиферацией и апоптозом в клетках яичников. Ведущими причинами, приводящими к снижению фертильности, бесплодию и к неудачам при ЭКО у пациенток с ожирением являются механизмы, способствующие формированию хронической ановуляции, задержке созревания ооцитов, снижению их качества и/или ведущие к изменению восприимчивости эндометрия. Данные эффекты могут быть вызваны дисбалансом концентраций лептина и адипонектина (избытком лептина и дефицитом адипонектина), привести к дисфункции эндометрия, нарушению имплантации и раннего эмбриогенеза. Данные изменения, в свою очередь, могут повлиять как на вероятность самостоятельного зачатия, так и на эффективность вспомогательных репродуктивных технологий и последующее вынашивание.

Таким образом, изучение потенциальных патогенетических путей регуляции фертильности при ожирении, одному из которых посвящен данный обзор, является актуальным направлением для дальнейшего изучения.

There is a great worldwide trend in the incidence of obesity, which is increasing with each passing year among all populations, including women of reproductive age. Given the impressive list of diseases associated with obesity, as well as the negative inverse correlation of the severity of obesity with fertility, this problem is global not only in the social sphere, but it also becomes demographically significant.

Along with other pathogenetic mechanisms leading to persistent anovulation, an imbalance in adipokine production by adipose tissue can also serve as one of the important links in the development of reproductive dysfunction. Despite apparent interest in this topic, a large number of previously discovered adipokines are still not studied. Among adipokines, the effects of adiponectin and leptin on reproductive function are best known. Alterations in adiponectin and leptin levels can affect hypothalamic-pituitary-gonadal signaling, folliculogenesis, oogenesis and steroidogenesis. In addition, leptin is involved in the initiation of puberty, regulation of the menstrual cycle, and changes the balance between proliferation and apoptosis in ovarian cells. The leading causes of reduced fertility, infertility, and IVF failure in obese patients are mechanisms that promote the formation of chronic anovulation, delay the maturation of oocytes, reduce their quality, and/or lead to changes in endometrial susceptibility. These effects can be caused by an imbalance in the concentrations of leptin and adiponectin (leptin excess and adiponectin deficiency), lead to endometrial dysfunction, disruption of implantation and early embryogenesis. These changes, in turn, can affect just as the likelihood of spontaneous conception, so the effectiveness of assisted reproductive technologies and subsequent gestation.

Thus, the study of potential pathogenetic pathways of fertility regulation in obesity, one of which is the subject of this review, is an important area for further study.

ожирениеадипонектинлептинановуляциябесплодиевспомогательные репродуктивные технологииоbesityadiponectinleptinanovulationinfertilityassisted reproductive technologiesРабота выполнена в рамках государственного задания, номер ЕГИСУ 121031000362-3ReferencesДедов И.И., Шестакова М.В., Мельниченко Г.А., и др. Междисциплинарные клинические рекомендации «Лечение ожирения и коморбидных заболеваний» // Ожирение и метаболизм. — 2021. — Т. 18. — №1. — С. 5-99. doi: https://doi.org/10.14341/omet12714Dedov II, Shestakova M V., Melnichenko GA, et al. Interdisciplinary clinical practice guidelines “Management of obesity and its comorbidities.” Obesity and metabolism. 2021;18(1):5-99. (In Russ.). doi: https://doi.org/10.14341/omet12714Obesity and overweight. Who.int [Internet]. 9 June 2021 [cited 13.01.2022]. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/Obesity and overweight. Who.int [Internet]. 9 June 2021 [cited 13.01.2022]. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/Цаллагова Е.В., Прилепская В.Н. Ожирение и здоровье женщины: от менархе до менопаузы // Гинекология. — 2019. — Т. 21. — №5. — С. 7-11. doi: https://doi.org/10.26442/20795696.2019.5.190732Tsallagova EV, Prilepskaya VN. Obesity and women’s health: from menarche to menopause. Gynecology. 2019;21(5): 7-11. (In Russ.). doi: https://doi.org/10.26442/20795696.2019.5.190732Zhu L, Zhou B, Zhu X, et al. Association Between Body Mass Index and Female Infertility in the United States: Data from National Health and Nutrition Examination Survey 2013–2018. Int J Gen Med. 2022;(15):1821-1831. doi: https://doi.org/10.2147/IJGM.S349874Zhu L, Zhou B, Zhu X, et al. Association Between Body Mass Index and Female Infertility in the United States: Data from National Health and Nutrition Examination Survey 2013–2018. Int J Gen Med. 2022;(15):1821-1831. doi: https://doi.org/10.2147/IJGM.S349874García-Ferreyra J, Carpio J, Zambrano M, et al. Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing In Vitro Fertilization procedures. JBRA Assist Reprod. 2021;25(3):394-402. doi: https://doi.org/10.5935/1518-0557.20200105García-Ferreyra J, Carpio J, Zambrano M, et al. Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing In Vitro Fertilization procedures. JBRA Assist Reprod. 2021;25(3):394-402. doi: https://doi.org/10.5935/1518-0557.20200105Silvestris E, de Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol. 2018;16(1):22. doi: https://doi.org/10.1186/s12958-018-0336-zSilvestris E, de Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol. 2018;16(1):22. doi: https://doi.org/10.1186/s12958-018-0336-zMaiborodina D, Antonenko M, Komisarenko Y, Stolyar V. Adipocytokines leptin and adiponeсtin as predictors of generalized periodontitis associated with obesity. Georgian Med News. 2021;(312):42-46.Maiborodina D, Antonenko M, Komisarenko Y, Stolyar V. Adipocytokines leptin and adiponeсtin as predictors of generalized periodontitis associated with obesity. Georgian Med News. 2021;(312):42-46.Дубинская Е.Д., Алешкина Е.В., Гаспаров А.С., и др. Ожирение и фертильность // Вопросы гинекологии, акушерства и перинатологии. — 2018. — Т. 17. — №6. — С. 76-84. doi: https://doi.org/10.20953/1726-1678-2018-6-76-84Dubinskaya ED, Aleshkina EV, Gasparov AS, et al. Obesity and fertility. Vopr Ginekol akušerstva i Perinatol. 2018;17(6):76-84. (In Russ.). doi: https://doi.org/10.20953/1726-1678-2018-6-76-84Khanna D, Rehman A. Pathophysiology of obesity. 2022 Jun 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.Khanna D, Rehman A. Pathophysiology of obesity. 2022 Jun 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.Lainez NM, Coss D. Obesity, neuroinflammation, and reproductive function. Endocrinology. 2019;160(11):2719-2736. doi: https://doi.org/10.1210/en.2019-00487Lainez NM, Coss D. Obesity, neuroinflammation, and reproductive function. Endocrinology. 2019;160(11):2719-2736. doi: https://doi.org/10.1210/en.2019-00487McPherson RA, Pincus MR. Henry’s clinical diagnosis and management by laboratory methods, 24th Edition. Elsevier; 2021. 974 p.McPherson RA, Pincus MR. Henry’s clinical diagnosis and management by laboratory methods, 24th Edition. Elsevier; 2021. 974 p.Kurowska P, Mlyczyńska E, Dawid M, et al. Adipokines change the balance of proliferation/apoptosis in the ovarian cells of human and domestic animals: A comparative review. Anim Reprod Sci. 2021;(228):106737. doi: https://doi.org/10.1016/j.anireprosci.2021.106737Kurowska P, Mlyczyńska E, Dawid M, et al. Adipokines change the balance of proliferation/apoptosis in the ovarian cells of human and domestic animals: A comparative review. Anim Reprod Sci. 2021;(228):106737. doi: https://doi.org/10.1016/j.anireprosci.2021.106737Barbe A, Bongrani A, Mellouk N, et al. Mechanisms of adiponectin action in fertility: an overview from gametogenesis to gestation in humans and animal models in normal and pathological conditions. Int J Mol Sci. 2019;20(7):1526. doi: https://doi.org/10.3390/ijms20071526Barbe A, Bongrani A, Mellouk N, et al. Mechanisms of adiponectin action in fertility: an overview from gametogenesis to gestation in humans and animal models in normal and pathological conditions. Int J Mol Sci. 2019;20(7):1526. doi: https://doi.org/10.3390/ijms20071526Estienne A, Brossaud A, Reverchon M, et al. Adipokines expression and effects in oocyte maturation, fertilization and early embryo development: lessons from mammals and birds. Int J Mol Sci. 2020;21(10):3581. doi: https://doi.org/10.3390/ijms21103581Estienne A, Brossaud A, Reverchon M, et al. Adipokines expression and effects in oocyte maturation, fertilization and early embryo development: lessons from mammals and birds. Int J Mol Sci. 2020;21(10):3581. doi: https://doi.org/10.3390/ijms21103581Елагин И.Б., Оразов М.Р., Семенов П.А. Патогенез нарушения фертильности у женщин с ожирением // Трудный пациент. — 2020. — Т. 18. — №1-2. — С. 36-43. doi: https://doi.org/10.24411/2074-1995-2020-10007Elagin IB, Orazov MR, Semyonov PA. Pathogenesis of impaired fertility in obese women. Difficult patient. 2020;18(1-2):36-43. (In Russ.). doi: https://doi.org/10.24411/2074-1995-2020-10007Alam Q, Alam MZ, Mushtaq G, et al. Inflammatory Process in Alzheimer’s and Parkinson’s Diseases: Central Role of Cytokines. Curr Pharm Des. 2016;22(5):541-548. doi: https://doi.org/10.2174/1381612822666151125000300Alam Q, Alam MZ, Mushtaq G, et al. Inflammatory Process in Alzheimer’s and Parkinson’s Diseases: Central Role of Cytokines. Curr Pharm Des. 2016;22(5):541-548. doi: https://doi.org/10.2174/1381612822666151125000300Goldsammler M, Merhi Z, Buyuk E. Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis. Reprod Biol Endocrinol. 2018;16(1):45. doi: https://doi.org/10.1186/s12958-018-0366-6Goldsammler M, Merhi Z, Buyuk E. Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis. Reprod Biol Endocrinol. 2018;16(1):45. doi: https://doi.org/10.1186/s12958-018-0366-6Nikanfar S, Oghbaei H, Rastgar Rezaei Y, et al. Role of adipokines in the ovarian function: Oogenesis and steroidogenesis. J Steroid Biochem Mol Biol. 2021;209(6):105852. doi: https://doi.org/10.1016/j.jsbmb.2021.105852Nikanfar S, Oghbaei H, Rastgar Rezaei Y, et al. Role of adipokines in the ovarian function: Oogenesis and steroidogenesis. J Steroid Biochem Mol Biol. 2021;209(6):105852. doi: https://doi.org/10.1016/j.jsbmb.2021.105852Bilbao MG, Di Yorio MP, Galarza RA, et al. Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats. Reproduction. 2015;149(4):357-366. doi: https://doi.org/10.1530/REP-14-0536Bilbao MG, Di Yorio MP, Galarza RA, et al. Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats. Reproduction. 2015;149(4):357-366. doi: https://doi.org/10.1530/REP-14-0536Cheng L, Shi H, Jin Y, et al. Adiponectin deficiency leads to female subfertility and ovarian dysfunctions in mice. Endocrinology. 2016;157(12):4875-4887. doi: https://doi.org/10.1210/en.2015-2080Cheng L, Shi H, Jin Y, et al. Adiponectin deficiency leads to female subfertility and ovarian dysfunctions in mice. Endocrinology. 2016;157(12):4875-4887. doi: https://doi.org/10.1210/en.2015-2080Merhi Z, Bazzi AA, Bonney EA, Buyuk E. Role of adiponectin in ovarian follicular development and ovarian reserve. Biomed Rep. 2019;1(1):1-5. doi: https://doi.org/10.3892/br.2019.1213Merhi Z, Bazzi AA, Bonney EA, Buyuk E. Role of adiponectin in ovarian follicular development and ovarian reserve. Biomed Rep. 2019;1(1):1-5. doi: https://doi.org/10.3892/br.2019.1213Chappaz E, Albornoz MS, Campos D, et al. Adiponectin enhances in vitro development of swine embryos. Domest Anim Endocrinol. 2008;35(2):198-207. doi: https://doi.org/10.1016/j.domaniend.2008.05.007Chappaz E, Albornoz MS, Campos D, et al. Adiponectin enhances in vitro development of swine embryos. Domest Anim Endocrinol. 2008;35(2):198-207. doi: https://doi.org/10.1016/j.domaniend.2008.05.007Gomes ET, Costa JAS, Silva DMF, et al. Effects of adiponectin during in vitro maturation of goat oocytes: MEK 1/2 pathway and gene expression pattern. Reprod Domest Anim. 2018;53(6):1323-1329. doi: https://doi.org/10.1111/rda.13251Gomes ET, Costa JAS, Silva DMF, et al. Effects of adiponectin during in vitro maturation of goat oocytes: MEK 1/2 pathway and gene expression pattern. Reprod Domest Anim. 2018;53(6):1323-1329. doi: https://doi.org/10.1111/rda.13251Ledoux S, Campos DB, Lopes FL, et al. Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology. 2006;147(11):5178-5186. doi: https://doi.org/10.1210/en.2006-0679Ledoux S, Campos DB, Lopes FL, et al. Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology. 2006;147(11):5178-5186. doi: https://doi.org/10.1210/en.2006-0679Comim FV, Gutierrez K, Bridi A, et al. Effects of adiponectin including reduction of androstenedione secretion and ovarian oxidative stress parameters in vivo. PLoS One. 2016;11(5):e0154453. doi: https://doi.org/10.1371/journal.pone.0154453Comim FV, Gutierrez K, Bridi A, et al. Effects of adiponectin including reduction of androstenedione secretion and ovarian oxidative stress parameters in vivo. PLoS One. 2016;11(5):e0154453. doi: https://doi.org/10.1371/journal.pone.0154453Smolinska N, Szeszko K, Dobrzyn K, et al. Transcriptomic Analysis of Porcine Endometrium during Implantation after In Vitro Stimulation by Adiponectin. Int J Mol Sci. 2019;20(6):1335. doi: https://doi.org/10.3390/ijms20061335Smolinska N, Szeszko K, Dobrzyn K, et al. Transcriptomic Analysis of Porcine Endometrium during Implantation after In Vitro Stimulation by Adiponectin. Int J Mol Sci. 2019;20(6):1335. doi: https://doi.org/10.3390/ijms20061335Lin K, Sun X, Wang X, et al. Circulating adipokine levels in nonobese women with polycystic ovary syndrome and in nonobese control women: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;11:537809. doi: https://doi.org/10.3389/fendo.2020.537809Lin K, Sun X, Wang X, et al. Circulating adipokine levels in nonobese women with polycystic ovary syndrome and in nonobese control women: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;11:537809. doi: https://doi.org/10.3389/fendo.2020.537809Ведзижева Э.Р., Успенская Ю.Б., Гитель Е.П., Кузнецова И.В. Влияние ожирения и дислипидемии на выработку грелина и лептина у женщин репродуктивного возраста. Гинекология. 2017;19(2):29-33.Vedzizheva ER, Uspenskaya YuB, Gitel EP, Kuznetsova IV. The influence of obesity and dyslipidemia on ghrelin production in women of reproductive age. Gynecology. 2017; 19 (2): 29–33 (In Russ.).Kurowska P, Mlyczyńska E, Dawid M, et al. Adipokines change the balance of proliferation/apoptosis in the ovarian cells of human and domestic animals: A comparative review. Anim Reprod Sci. 2021;228:106737. doi: https://doi.org/10.1016/j.anireprosci.2021.106737Kurowska P, Mlyczyńska E, Dawid M, et al. Adipokines change the balance of proliferation/apoptosis in the ovarian cells of human and domestic animals: A comparative review. Anim Reprod Sci. 2021;228:106737. doi: https://doi.org/10.1016/j.anireprosci.2021.106737Balogh O, Kowalewski MP, Reichler IM. Leptin and leptin receptor gene expression in the canine corpus luteum during diestrus, pregnancy and after aglepristone-induced luteolysis. Reprod Domest Anim. 2012;47(S6):40-42. doi: https://doi.org/10.1111/rda.12005Balogh O, Kowalewski MP, Reichler IM. Leptin and leptin receptor gene expression in the canine corpus luteum during diestrus, pregnancy and after aglepristone-induced luteolysis. Reprod Domest Anim. 2012;47(S6):40-42. doi: https://doi.org/10.1111/rda.12005Рыжов Ю.Р., Шпаковская А.О., Гзгян А.М. Роль лептина в регуляции репродуктивной системы и перспективы его использования во вспомогательных репродуктивных технологиях // Проблемы репродукции. — 2020. — Т. 26. — №2. — С. 53-61. doi: https://doi.org/10.17116/repro20202602153Ryzhov JR, Shpakov AO, Gzgzyan AM. Leptin role in reproductive system regulation and its perspectives in assisted reproductive technologies. Problemy Reproduktsii. 2020;26(2):53. (In Russ.). doi: https://doi.org/10.17116/repro20202602153Карелина О.Б., Артымук Н.В. Особенности содержания лептина у беременных с ожирением и их новорожденных // Фундаментальная и клиническая медицина. — 2017. — Т. 2. — №3. — С. 21-27.Karelina OB, Artymuk NV. leptin serum level in women with obesity do not define leptin cord blood level in their newborns. Fundamental and Clinical Medicine. 2017;2(3):21-27. (In Russ.).Reshma R, Mishra SR, Thakur N, et al. Modulatory role of leptin on ovarian functions in water buffalo (Bubalus bubalis). Theriogenology. 2016;86(7):1720-1739. doi: https://doi.org/10.1016/j.theriogenology.2016.05.029Reshma R, Mishra SR, Thakur N, et al. Modulatory role of leptin on ovarian functions in water buffalo (Bubalus bubalis). Theriogenology. 2016;86(7):1720-1739. doi: https://doi.org/10.1016/j.theriogenology.2016.05.029Bernardi O, Estienne A, Reverchon M, et al. Adipokines in metabolic and reproductive functions in birds: An overview of current knowns and unknowns. Mol Cell Endocrinol. 2021;534(2):111370. doi: https://doi.org/10.1016/j.mce.2021.111370Bernardi O, Estienne A, Reverchon M, et al. Adipokines in metabolic and reproductive functions in birds: An overview of current knowns and unknowns. Mol Cell Endocrinol. 2021;534(2):111370. doi: https://doi.org/10.1016/j.mce.2021.111370Evans MC, Lord RA, Anderson GM. Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends? Int J Mol Sci. 2021;22(17):9210. doi: https://doi.org/10.3390/ijms22179210Evans MC, Lord RA, Anderson GM. Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends? Int J Mol Sci. 2021;22(17):9210. doi: https://doi.org/10.3390/ijms22179210Peng Y, Yang H, Song J, et al. Elevated Serum Leptin Levels as a Predictive Marker for Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2022;13(2):111370. doi: https://doi.org/10.3389/fendo.2022.845165Peng Y, Yang H, Song J, et al. Elevated Serum Leptin Levels as a Predictive Marker for Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2022;13(2):111370. doi: https://doi.org/10.3389/fendo.2022.845165Anifandis G, Koutselini E, Stefanidis I, et al. Serum and follicular fluid leptin levels are correlated with human embryo quality. Reproduction. 2005;130(6):917-921. doi: https://doi.org/10.1530/rep.1.00705Anifandis G, Koutselini E, Stefanidis I, et al. Serum and follicular fluid leptin levels are correlated with human embryo quality. Reproduction. 2005;130(6):917-921. doi: https://doi.org/10.1530/rep.1.00705Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism. 2015;64(1):13-23. doi: https://doi.org/10.1016/j.metabol.2014.09.010Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism. 2015;64(1):13-23. doi: https://doi.org/10.1016/j.metabol.2014.09.010Castro NP, Euclydes VV, Simões FA, et al. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity. Nutrients. 2017;9(3):182. doi: https://doi.org/10.3390/nu9030182Castro NP, Euclydes VV, Simões FA, et al. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity. Nutrients. 2017;9(3):182. doi: https://doi.org/10.3390/nu9030182Patenaude J, Lacerte G, Lacroix M, et al. Associations of Maternal Leptin with Neonatal Adiposity Differ according to Pregravid Weight. Neonatology. 2017;111(4):344-352. doi: https://doi.org/10.1159/000454756Patenaude J, Lacerte G, Lacroix M, et al. Associations of Maternal Leptin with Neonatal Adiposity Differ according to Pregravid Weight. Neonatology. 2017;111(4):344-352. doi: https://doi.org/10.1159/000454756Estienne A, Bongrani A, Reverchon M, et al. Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models. Int J Mol Sci. 2019;20(18):4431. doi: https://doi.org/10.3390/ijms20184431Estienne A, Bongrani A, Reverchon M, et al. Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models. Int J Mol Sci. 2019;20(18):4431. doi: https://doi.org/10.3390/ijms20184431Cabral A, López Soto EJ, Epelbaum J, Perelló M. Is Ghrelin Synthesized in the Central Nervous System? Int J Mol Sci. 2017;18(3):638. doi: https://doi.org/10.3390/ijms18030638Cabral A, López Soto EJ, Epelbaum J, Perelló M. Is Ghrelin Synthesized in the Central Nervous System? Int J Mol Sci. 2017;18(3):638. doi: https://doi.org/10.3390/ijms18030638Uriarte M, De Francesco PN, Fernández G, et al. Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms. Mol Cell Endocrinol. 2021;538(2):111449. doi: https://doi.org/10.1016/j.mce.2021.111449Uriarte M, De Francesco PN, Fernández G, et al. Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms. Mol Cell Endocrinol. 2021;538(2):111449. doi: https://doi.org/10.1016/j.mce.2021.111449Chan JL, Bullen J, Lee JH, et al. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab. 2004;89(1):335-343. doi: https://doi.org/10.1210/jc.2003-031412Chan JL, Bullen J, Lee JH, et al. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab. 2004;89(1):335-343. doi: https://doi.org/10.1210/jc.2003-031412Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A. 2004;101(13):4679-4684. doi: https://doi.org/10.1073/pnas.0305930101Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci U S A. 2004;101(13):4679-4684. doi: https://doi.org/10.1073/pnas.0305930101Schalla MA, Stengel A. The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction. Int J Mol Sci. 2021;22(20):11059. doi: https://doi.org/10.3390/ijms222011059Schalla MA, Stengel A. The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction. Int J Mol Sci. 2021;22(20):11059. doi: https://doi.org/10.3390/ijms222011059Sominsky L, Goularte JF, Andrews ZB, Spencer SJ. Acylated Ghrelin Supports the Ovarian Transcriptome and Follicles in the Mouse: Implications for Fertility. Front Endocrinol (Lausanne). 2019;9(2):111449. doi: https://doi.org/10.3389/fendo.2018.00815Sominsky L, Goularte JF, Andrews ZB, Spencer SJ. Acylated Ghrelin Supports the Ovarian Transcriptome and Follicles in the Mouse: Implications for Fertility. Front Endocrinol (Lausanne). 2019;9(2):111449. doi: https://doi.org/10.3389/fendo.2018.00815Jang H, Na Y, Hong K, et al. Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27 Kip1 promoter in primordial follicles. J Pineal Res. 2017;63(3):e12432. doi: https://doi.org/10.1111/jpi.12432Jang H, Na Y, Hong K, et al. Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27 Kip1 promoter in primordial follicles. J Pineal Res. 2017;63(3):e12432. doi: https://doi.org/10.1111/jpi.12432Kheradmand A, Roshangar L, Taati M, Sirotkin AV. Morphometrical and intracellular changes in rat ovaries following chronic administration of ghrelin. Tissue Cell. 2009;41(5):311-317. doi: https://doi.org/10.1016/j.tice.2009.01.002Kheradmand A, Roshangar L, Taati M, Sirotkin AV. Morphometrical and intracellular changes in rat ovaries following chronic administration of ghrelin. Tissue Cell. 2009;41(5):311-317. doi: https://doi.org/10.1016/j.tice.2009.01.002Luque EM, Carlini VP, Vincenti LM, et al. Effects of hexarelin (a ghrelin analogue) on fertilisation and the pre- and postnatal development of mice. Reprod Fertil Dev. 2010;22(6):926-938. doi: https://doi.org/10.1071/RD09231Luque EM, Carlini VP, Vincenti LM, et al. Effects of hexarelin (a ghrelin analogue) on fertilisation and the pre- and postnatal development of mice. Reprod Fertil Dev. 2010;22(6):926-938. doi: https://doi.org/10.1071/RD09231Xu XL, Bai JH, Feng T, et al. N-octanoylated ghrelin peptide inhibits bovine oocyte meiotic resumption. Gen Comp Endocrinol. 2018;263(3):7-11. doi: https://doi.org/10.1016/j.ygcen.2018.04.016Xu XL, Bai JH, Feng T, et al. N-octanoylated ghrelin peptide inhibits bovine oocyte meiotic resumption. Gen Comp Endocrinol. 2018;263(3):7-11. doi: https://doi.org/10.1016/j.ygcen.2018.04.016Chouzouris TM, Dovolou E, Krania F, et al. Effects of ghrelin on activation of Akt1 and ERK1/2 pathways during in vitro maturation of bovine oocytes. Zygote. 2017;25(2):183-189. doi: https://doi.org/10.1017/S096719941700003XChouzouris TM, Dovolou E, Krania F, et al. Effects of ghrelin on activation of Akt1 and ERK1/2 pathways during in vitro maturation of bovine oocytes. Zygote. 2017;25(2):183-189. doi: https://doi.org/10.1017/S096719941700003XDu C, Li H, Cao G, et al. Expression of the orexigenic peptide ghrelin and the type 1a growth hormone secretagogue receptor in sheep oocytes and pre-implantation embryos produced in vitro. Reprod Domest Anim. 2010;45(1):92-98. doi: https://doi.org/10.1111/j.1439-0531.2008.01259.xDu C, Li H, Cao G, et al. Expression of the orexigenic peptide ghrelin and the type 1a growth hormone secretagogue receptor in sheep oocytes and pre-implantation embryos produced in vitro. Reprod Domest Anim. 2010;45(1):92-98. doi: https://doi.org/10.1111/j.1439-0531.2008.01259.xLuque EM, Torres PJ, de Loredo N, et al. Role of ghrelin in fertilization, early embryo development, and implantation periods. Reproduction. 2014;148(2):159-167. doi: https://doi.org/10.1530/REP-14-0129Luque EM, Torres PJ, de Loredo N, et al. Role of ghrelin in fertilization, early embryo development, and implantation periods. Reproduction. 2014;148(2):159-167. doi: https://doi.org/10.1530/REP-14-0129Wang D, Yang Y, Song Y, et al. The Effect of Ghrelin on the Maturation of Sheep Oocytes and Early Embryonic Development In Vitro. Animals (Basel). 2022;12(9):1158. doi: https://doi.org/10.3390/ani12091158Wang D, Yang Y, Song Y, et al. The Effect of Ghrelin on the Maturation of Sheep Oocytes and Early Embryonic Development In Vitro. Animals (Basel). 2022;12(9):1158. doi: https://doi.org/10.3390/ani12091158Li L, Ferin M, Sauer MV, Lobo RA. Serum and follicular fluid ghrelin levels negatively reflect human oocyte quality and in vitro embryo development. Fertil Steril. 2011;96(5):1116-1120. doi: https://doi.org/10.1016/j.fertnstert.2011.08.017Li L, Ferin M, Sauer MV, Lobo RA. Serum and follicular fluid ghrelin levels negatively reflect human oocyte quality and in vitro embryo development. Fertil Steril. 2011;96(5):1116-1120. doi: https://doi.org/10.1016/j.fertnstert.2011.08.017Tanaka K, Minoura H, Isobe T, et al. Ghrelin Is Involved in the Decidualization of Human Endometrial Stromal Cells. J Clin Endocrinol Metab. 2003;88(5):2335-2340. doi: https://doi.org/10.1210/jc.2002-021024Tanaka K, Minoura H, Isobe T, et al. Ghrelin Is Involved in the Decidualization of Human Endometrial Stromal Cells. J Clin Endocrinol Metab. 2003;88(5):2335-2340. doi: https://doi.org/10.1210/jc.2002-021024Martin JR, Lieber SB, McGrath J, et al. Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. Endocrinology. 2011;152(5):2060-2066. doi: https://doi.org/10.1210/en.2010-1485Martin JR, Lieber SB, McGrath J, et al. Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. Endocrinology. 2011;152(5):2060-2066. doi: https://doi.org/10.1210/en.2010-1485Xu L, Shi Y, Gu J, et al. Association between ghrelin gene variations, body mass index, and waist-to-hip ratio in patients with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2014;122(3):144-148. doi: https://doi.org/10.1055/s-0034-1367024Xu L, Shi Y, Gu J, et al. Association between ghrelin gene variations, body mass index, and waist-to-hip ratio in patients with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2014;122(3):144-148. doi: https://doi.org/10.1055/s-0034-1367024Schöfl C, Horn R, Schill T, et al. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(10):4607-4610. doi: https://doi.org/10.1210/jc.2002-020505Schöfl C, Horn R, Schill T, et al. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(10):4607-4610. doi: https://doi.org/10.1210/jc.2002-020505

The authors declare that there are no conflicts of interest present.