The role of the leptin in reproduction

Current Opinion in Obstetrics and Gynecology

Volumn 18, Issue 3, 2006, Pages 297-303

  Cervero, Ana ^a   Domínguez, Francisco ^a   Horcajadas, José A ^a   Quiñonero, Alicia ^a   Pellicer, Antonio ^a   Simón, Carlos ^a,b  

^a UNIVERSITY OF VALENCIA   (Spain)

^b Fundacion IVI   (Spain)

Author keywords

Embryo; Endometrium; Implantation; Leptin; Leptin receptor

Indexed keywords

GONADORELIN; LEPTIN; LEPTIN RECEPTOR; LUTEINIZING HORMONE;

EMBRYO DEVELOPMENT; ENDOMETRIUM; GONADORELIN RELEASE; HUMAN; HYPOPHYSIS ADRENAL SYSTEM; IMPLANTATION; LUTEINIZING HORMONE RELEASE; NEUROENDOCRINE SYSTEM; NONHUMAN; NUTRITIONAL STATUS; OVARY; OVARY POLYCYSTIC DISEASE; PREECLAMPSIA; PREGNANCY; PREIMPLANTATION EMBRYO; PRIORITY JOURNAL; PROTEIN FUNCTION; PUBERTY; REPRODUCTION; REVIEW; STATISTICAL SIGNIFICANCE;

EMBRYO IMPLANTATION; ENDOMETRIUM; FEMALE; HUMANS; LEPTIN; OVARY; PREGNANCY; REPRODUCTION;

EID: 33744988572     PISSN: 1040872X     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.gco.0000193004.35287.89     Document Type: Review

References (47)

1. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372:425-432.
2. Chen H, Charlat O, Tartaglia LA, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84:491-495.
3. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996; 12:318-320.
4. Cervero A, Horcajadas JA, Dominguez F, et al. Leptin system in embryo development and implantation: a protein in search of a function. Reprod Biomed Online 2005; 10:217-223. This is a review summarising the important role of the leptin system in the implantation process.
5. Tataranni PA, Monroe MB, Dueck CA, et al. Adiposity, plasma leptin concentration and reproductive function in active and sedentary females. Int J Obes Relat Metab Disord 1997; 21:818-821.
6. De Luca C, Kowalski TJ, Zhang Y, et al. Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest 2005; 115:3484-3493. This research article described how a combination of leptin receptor transgenes, with potentially complementary expression patterns, prevents the db/db phenotype in mouse, restoring body weight and fertility in these animals.
7. Lebrethon MC, Vandersmissen E, Gerard A, et al. Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimulatory effect on the rat gonadotropin-releasing hormone pulse generator in vitro. J Neuroendocrinol 2000; 12:383-385.
8. Yu WH, Walczewska A, Karanth S, McCann SM. Nitric oxide mediates leptin-induced luteinizing hormone-releasing hormone (LHRH) and LHRH and leptin-induced LH release from the pituitary gland. Endocrinology 1997; 138:5055-5058.
9. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351:987-997. A remarkable study in which the administration of recombinant leptin to women with hypothalamic amenorrhoea improved their reproductive and neuroendocrine function compared with control subjects who had not been treated.
10. Cunningham MJ, Clifton DK, Steiner RA. Leptin's actions on the reproductive axis: perspectives and mechanisms. Biol Reprod 1999; 60:216-222.
11. Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa. Lancet 2-8 July 2005; 366 (9479):74-85. This review outlines the role of leptin in neuroendocrine function and the importance of this molecule in the pathophysiology of energy-deficient states such as hypothalamic amenorrhoea and anorexia nervosa.
12. Chehab FF, Mounzih K, Lu R, Lim ME. Early onset of reproductive function in normal female mice treated with leptin. Science 1997; 275:88-90.
13. Gruaz NM, Lalaoui M, Pierroz DD, et al. Chronic administration of leptin into the lateral ventricle induces sexual maturation in severely food-restricted female rats. J Neuroendocrinol 1998; 10:627-633.
14. Jaruratanasirikul S, Mo-suwan L, Lebel L. Growth pattern and age at menarche of obese girls in a transitional society. J Pediatr Endocrinol Metab 1997; 10:487-490.
15. Garcia-Mayor RV, Andrade MA, Rios M, et al. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal- hormones, and pubertal stage. J Clin Endocrinol Metab 1997; 82:2849-2855.
16. Plant TM, Durrant AR. Circulating leptin does not appear to provide a signal for triggering the initiation of puberty in the male rhesus monkey (Macaca mulatta). Endocrinology 1997; 138:4505-4508.
17. Andreelli F, Hanaire-Broutin H, Laville M, et al. Normal reproductive function in leptin-deficient patients with lipoatropic diabetes. J Clin Endocrinol Metab 2000; 85:715-719.
18. Fedorcsak P, Storeng R, Dale PO, et al. Leptin and leptin binding activity in the preovulatory follicle of polycystic ovary syndrome patients. Scand J Clin Lab Invest 2000; 60:649-655.
19. Ryan NK, Woodhouse CM, Van der Hoek KH, et al. Expression of leptin and its receptor in the murine ovary: possible role in the regulation of oocyte maturation. Biol Reprod 2002; 66:1548-1554.
20. Huang HF, Wang B, Yang XF, et al. Nitric oxide mediates inhibitory effect of leptin on insulin-like growth factor I augmentation of 17beta-estradiol production in human granulosa cells. Biol Reprod 2005; 72:102-106. This study suggests that the inhibitory effect of leptin in the production of oestradiol by human granulosa cells is mediated via nitric oxide.
21. Kitawaki J, Kusuki I, Koshiba H, et al. Leptin directly stimulates aromatase activity in human luteinized granulosa cells. Mol Hum Reprod 1999; 5:708-713.
22. Swain JE, Dunn RL, McConnell D, et al. Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development. Biol Reprod 2004; 71:1446-1452.
23. Antczak M, Van Blerkom J. Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo. Mol Hum Reprod 1997; 3:1067-1086.
24. Kawamura K, Sato N, Fukuda J, et al. Leptin promotes the development of mouse preimplantation embryos in vitro. Endocrinology 2002; 143:1922-1931.
25. Cervero A, Horcajadas JA, Martin J, et al. The leptin system during human endometrial receptivity and preimplantation development. J Clin Endocrinol Metab 2004; 89:2442-2451. This is the first paper demonstrating leptin and leptin receptor expression during the development of human embryonic preimplantation. Moreover, it describes the expression pattern of long and short isoforms of leptin receptor in the human endometrium throughout the menstrual cycle.
26. Craig J, Zhu H, Dyce PW, et al. Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway. Endocrinology 2004; 145:5355-5363. This study demonstrated that the leptin receptor is expressed in the porcine oocyte and that leptin facilitates oocyte maturation via the mitogen-activated protein kinase pathway.
27. Boelhauve M, Sinowatz F, Wolf E, Paula-Lopes FF. Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts. Biol Reprod 2005; 73:737-744. This work shows that leptin treatment during bovine oocyte maturation improves developmental potential, resulting in increased development to the blastocyst stage with reduced numbers of apoptotic cells.
28. Matsuoka T, Tahara M, Yokoi T, et al. Tyrosine phosphorylation of STAT3 by leptin through leptin receptor in mouse metaphase 2 stage oocyte. Biochem Biophys Res Commun 1999; 256:480-484.
29. Craig JA, Zhu H, Dyce PW, et al. Leptin enhances porcine preimplantation embryo development in vitro. Mol Cell Endocrinol 2005; 229:141-147. This study demonstrates that the addition of leptin to porcine embryo culture medium increases the proportion of embryos reaching the blastocyst stage, suggesting that leptin plays a role in the development of porcine preimplantation embryos.
30. Yang YJ, Cao YJ, Bo SM, et al. Leptin-directed embryo implantation: Leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells. Anim. Reprod. Sci. 2006; 92:155-167.
31. Fedorcsak P, Storeng R. Effects of leptin and leukemia inhibitory factor on preimplantation development and STAT3 signaling of mouse embryos in vitro. Biol Reprod 2003; 69:1531-1538.
32. Gonzalez 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; 85:4883-4888.
33. Yoon SJ, Cha KY, Lee KA. Leptin receptors are down-regulated in uterine implantation sites compared to interimplantation sites. Mol Cell Endocrinol 2005; 232:27-35. This paper reports that the leptin receptor is differentially regulated in implantation and interimplantation sites, suggesting that leptin system may be a regulator of the implantation process.
34. Ramos MP, Rueda BR, Leavis PC, Gonzalez RR. Leptin serves as an upstream activator of an obligatory signaling cascade in the embryo-implantation process. Endocrinology 2005; 146:694-701. This paper demonstrates how a disruption of leptin signalling reduces mouse implantation and decreases IL-1 receptor type I, LIF receptor, vascular endothelial growth factor receptor 2 and β3 integrin levels in mouse endometrium.
35. Gonzalez RR, Leary K, Petrozza JC, Leavis PC. Leptin regulation of the interleukin-1 system in human endometrial cells. Mol Hum Reprod 2003; 9:151-158.
36. Gonzalez RR, Rueda BR, Ramos MP, et al. Leptin-induced increase in leukemia inhibitory factor and its receptor by human endometrium is partially mediated by interleukin 1 receptor signaling. Endocrinology 2004; 145:3850-3857.
37. Malik NM, Carter ND, Murray JF, et al. Leptin requirement for conception, implantation, and gestation in the mouse. Endocrinology 2001; 142:5198-5202.
38. Schulz LC, Widmaier EP. The effect of leptin on mouse trophoblast cell invasion. Biol Reprod 2004; 71:1963-1967. This work shows that leptin stimulates mouse trophoblast cell invasion and that this invasion is prevented by an inhibitor of metalloproteinases. These findings suggest that this molecule may play a role in establishment of the placenta and that this function is dependent on metalloproteinases.
39. Henson MC, Castracane VD. Leptin in pregnancy: an update. Biol. Reprod. 2006; 74:218-229.
40. Malik NM, Carter ND, Wilson CA, et al. Leptin expression in the fetus and placenta during mouse pregnancy. Placenta 2005; 26:47-52.
41. Ladyman SR, Grattan DR. Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat. Endocrinology 2005; 146: 3868-3874. This significant research article shows a significant reduction in leptin receptor mRNA levels in the ventromedial nucleus and choroid plexus of the hypothalamus, respectively, during pregnancy. These results indicate that this is the hypothalamic site involved in pregnancy-induced leptin resistance and that a reduced transport of leptin could also be responsible for the leptin resistance.
42. Hendler I, Blackwell SC, Mehta SH, et al. The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia. Am J Obstet Gynecol 2005; 193:979-983.
43. Naruse K, Yamasaki M, Umekage H, et al. Peripheral blood concentrations of adiponectin, an adipocyte-specific plasma protein, in normal pregnancy and preeclampsia. J Reprod Immunol 2005; 65:65-75. This study shows that women with pre-eclampsia present higher serum leptin concentrations than women without.
44. Chappell LC, Seed PT, Briley A, et al. A longitudinal study of biochemical variables in women at risk of preeclampsia. Am J Obstet Gynecol 2002; 187:127-136.
45. Challier J, Galtier M, Bintein T, et al. Placental leptin receptor isoforms in normal and pathological pregnancies. Placenta 2003; 24:92-99.
46. Li RH, Poon SC, Yu MY, Wong YF. Expression of placental leptin and leptin receptors in preeclampsia. Int J Gynecol Pathol 2004; 23:378-385.
47. Lindheim SR, Sauer MV, Carmina E, et al. Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology. Fertil Steril 2000; 73:493-498.