|Year : 2017 | Volume
| Issue : 1 | Page : 9-14
Umbilical cord blood leptin concentration - What does it imply?
Harish C Chandramoorthy1, Ahmed Al-Hakami1, Abdullah Abu Sham2
1 Center for Stem Cell Research; Department of Microbiology & Parasitology, College of Medicine, King Khalid University, Abha, K.S.A
2 Department of Obstetrics & Gynecology, College of Medicine, King Khalid University, Abha, K.S.A
|Date of Web Publication||13-Aug-2020|
MSc, PhD Harish C Chandramoorthy
College of Medicine, King Khalid University, Abha
Source of Support: None, Conflict of Interest: None
Objective: The significance of the placental or umbilical cord leptin levels remains unresolved in spite of their well-documented function. In the current study we investigated, whether, leptin concentration that mirrors the fetal health is influenced by type of birth, placental weight, cord length, sex, weight, pO2 and pH parameters. Methods: Umbilical cord blood samples were collected post placental delivery (n=40) from both normal and caesarian deliveries with all demographical information. Leptin concentration was determined form cord blood plasma, while fresh cord blood was used for blood gas analysis. Results: The average leptin concentrations of male and female fetal umbilical cord were 16.6 ± 1.6 and 18.2 ± 0.6 ng/ml respectively. The maximum threshold of the umbilical vein leptin concentrations were 15.3 ± 0.6 and 18.3 ± 1.2 ng/ml in male and females respectively. There was a direct relationship observed with the birthweight and leptin concentration. The mean pH 7.117 ± 0.02 and pO2 19.74 ± 2.01 mmHg did not significantly correlate with leptin levels. Discussion: Leptin concertation were significantly high in normal delivery than caesarian section. Placental weight or umbilical cord length did not affect the leptin concentration. We did not observe any significant alteration in pH or pO2 levels influencing leptin. However, the most remarkable correlation was leptin with birth weight, which explains the best utilization of the maternal fuel resources in the development of the fetus. We did observe a level in female babies. Conclusion: Overall, the placental leptin concentration mirrors the health status of the fetus and weight metabolism.
Keywords: Leptin, Placental leptin, Cord blood leptin, Fetal obesity, Umbilical cord blood markers
|How to cite this article:|
Chandramoorthy HC, Al-Hakami A, Sham AA. Umbilical cord blood leptin concentration - What does it imply?. King Khalid Univ J Health Sci 2017;2:9-14
|How to cite this URL:|
Chandramoorthy HC, Al-Hakami A, Sham AA. Umbilical cord blood leptin concentration - What does it imply?. King Khalid Univ J Health Sci [serial online] 2017 [cited 2021 Mar 7];2:9-14. Available from: https://www.kkujhs.org/text.asp?2017/2/1/9/291937
| Introduction|| |
Leptin was discovered in the year 1994. Leptin is a 16-kD protein encoded by the obese (ob) gene. Identifying, the genes regulated by leptin will improve our understanding on regulation of weight and appetite. It is known that during pregnancy, important changes occur in the body weight of the mother, which is caused by sodium and water retention and by an increase in body fat tissue, but the mechanisms that regulate maternal and fetal changes in fat mass are not clearly understood., Leptin is secreted in adipocytes as a regulatory hormone controlling food intake and energy expenditure. Any physiological imbalance in the production of leptin results in problems associated with obesity. Many genes at transcriptional levels control the leptin production and regulation., There are many functions attributed to the hormone leptin including regulation of ovarian function, oocyte maturation and embryo development, and in the implantation process. Further leptin is known to cross blood brain barrier and binds to specific receptors in the hypothalamus. These receptors produce a coordinated series of responses to match rates of energy utilization to regulate body weight causing a decrease in food intake and an increase in body temperature and energy expenditure. Hence, leptin resistance is a cardinal feature of human obesity.,, It represents a break down in the communication system between adipose tissue and the brain, which regulates stabilization of body weight on whole. Further leptin is known to be associated with functions associated with neuroendocrine function, angiogenesis,, bone formation and reproduction in both adults and neonates. In pregnancy, leptin is known to regulate fetal growth, placental angiogenesis and mobilization of maternal fat. It may be noted that serum leptin levels in pregnant women are significantly higher than in non-pregnant women.. The human placenta expresses high amounts of leptin mRNA and protein in early, mid, and late gestation, though adipocytes have not been found in placental tissue., Leptin produced in the placenta deems increase in the maternal blood particularly in the second trimester and decline postpartum. Abnormally high levels of leptin have been observed in in pregnancies complicated by conditions such as diabetes mellitus and pre-eclampsia., The role of leptin in fetal physiology is not clear, although cord blood values correlate significantly with birth weight.
Therefore many areas of leptin physiology remain to be investigated. Especially the role of leptin in fetal metabolism, insulin sensitivity, and its involvement in endocrine function are active areas for research. While the future for leptin as a diagnostic, prognostic, or therapeutic agent is not clear, its involvement in many areas of physiology undoubtedly makes this a new hormone, which requires extensive study in the future to understand its physiology.
The main objective of this study is to explore the importance of cord blood leptin concentration as a marker of fetal health as reflected by fetal weight at birth.
| Materials and Methods|| |
Umbilical cord blood samples (n=40) were collected from Abha maternity and children hospital after obtaining informed consent. The ethical clearance was obtained from the ethics committee at College of Medicine, King Khalid University (approval number REC # 2015-03-11). Cord blood serum was used to assess the leptin concentration at the stem cell unit, College of Medicine. Demographical data such as birth weight, sex, mode of delivery, placental weight and umbilical cord length were documented. Blood gas analysis were done immediately post cord blood collection at the hospital premises by routine standard procedure.
Leptin ELISA kit was purchased from Diagnostic Biochem Canada Inc. The assay was performed as per manufacturer instructions. Briefly the antibody coated microwell plate was incubated with known volume of cord blood serum, washed and re-incubated with sandwich antibody followed by substrate. The corrected readings were compared with standards and controls for calculating the concentration of Leptin in the cord blood samples.
The leptin data are represented as the mean ± standard deviation. Statistical significance between the samples and controls, calculated by student t test as applicable. A p < 0.05 was considered statistically significant. Graph Pad Prism 5 used for the statistical assessment.
| Results|| |
Among the variables examined, birth weight, but not the sex showed the highest degree of relationship with cord blood serum leptin concertation in newborns. Since we did not observe a significant difference in sex, though cord blood leptin from female babies were higher compared to the male, we merged male and female for the parameters like placental weight, umbilical cord length, pH and pO2. Placental weight and leptin concentration showed a highly significant correlation [Table 1]A, while umbilical cord length compared with leptin levels did not show significant correlation.
|Table 1: A. Leptin Conc Vs Placental Weight and UC Length. B Leptin Conc Vs pH and P02|
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The average leptin concentration of male and female fetal umbilical cord were 16.6 ± 1.6 and 18.2 ± 0.6 ng/ml respectively [Figure 1]. We observed a higher concentration of the leptin for female babies and could not correlate to statistically significant observation in the current study. The maximum threshold of the umbilical vein leptin concentrations were 15.3 ± 0.6 and 18.3 ± 1.2 ng/ml in male and females respectively [Figure 2]A, [Figure 2]B. Though as mentioned above, female newborn umbilical cord had significantly higher plasma leptin concentration than males. None of the samples showed leptin concentration more than 15.4 and 18.5 ng/ml in cord blood serum collected from both male and female babies respectively [Figure 2]A, [Figure 2]B.
|Figure 2: A. Leptin Threshold in Male (n = 16). B Leptin threshold in Female (n = 24)|
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Figures and Tables
The next parameter we measured was pH and pO2 levels of the freshly collected cord blood [Table 1]B. The mean pH 7.117 ± 0.02 and pO2 19.74 ± 2.01 mmHg did not significantly correlate with leptin levels. The pH of the cord blood irrespective of leptin concentration was within 6.5 to 7.2 and none showed less or above the depicted values [Table 1]B. The most significant correlation was between the birth weight and leptin concentration. Cord blood leptin concentration was directly proportional to the birth weight of infants [Figure 3]A, [Figure 3]B. An average age of 2.8 to 2.9 kg showed optimal leptin concentration compared to the low or obese in both male and female babies.
|Figure 3: A. Male birth weight Vs Leptin (n = 16). B. Female birth weight Vs Leptin threshold (n = 24)|
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| Discussion|| |
The significance of the current study is the use of the cord blood leptin as marker for fetal health. For instance, in the gynecologic surgery the serum leptin concentration is modified reflecting positive or negative impact on energy turnover. The same phenomenon is observed during caesarian,, reflecting the importance of the leptin concentration associated with women health. Our current study results did not show a statistical significant variation between male and female babies with slightly higher concentration of leptin observed in the female umbilical cord. These were consistent with range observed in various other studies. The significance of umbilical cord leptin concentration is regarded as indicator of gynecoobstetric diseases. Since leptin has multiple functions such as gonadal regulation, regulation of fetal-placental metabolism, actions in the endometrium, mammary gland, the concentration of the placental and umbilical cord leptin is very important during pre and post pregnancy stages. Recently the importance of the leptin and the knowledge of serum leptin concentration in the oncological diseases is going-up. Though we do not know the correlation of the leptin levels with cancer incidence, there are various reports explaining the modified leptin levels in the choriocarcinoma, Meigs’ syndrome and other tumors.
The relation between the fetal weight and leptin concentration is an indicator of the obesity at adulthood. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to affect the causes of human perinatal morbidity and mortality that are associated with abnormalities of fetal maturity and development, general concept growth, trophoblast endocrinology, and placental sufficiency. Further placental or cord leptin levels can be attributed to influence the physiology of female health issues pertaining to menstruation, pregnancy and lactation. There was a direct relationship observed with the birthweight and leptin concentration. These results were comparable with the published results of the studies done elsewhere.
The trend was so that, with increase in weight of the infant, the lower was the concentration of the cord blood leptin. This observation showed that increased fetal adipose tissue might decrease the leptin secretion at transcriptional level. Overall, the variation in the concentration of leptin between inviduals is mainly due to the environmental factors experienced by the mother during the course of gestation. This might be an influencing factor for higher weight babies or obese babies. Among the type of delivery, about 80% of the deliveries were normal and 20% were cesarean (data not shown). However, our data suggested that leptin levels were low in high weight babies, which is also reflected in some of the cesarean cases too, were due to eclampsia experienced by the women during delivery process. Hence, we could not determine any significance with the mode of the birth and leptin concentration. Further investigations in this area will be necessary to improve new knowledge and a better understanding of the actions about this hormone related to fetal and mother health.
| Conclusion|| |
Higher concentration of the leptin with positive birth weight correlates the best utilization of the maternal fuel resources in the development of the fetus. We do not know the reason for the increased leptin levels in female cord blood samples. Overall the placental leptin concentration mirrors the health status of the fetus.
| Acknowledgment|| |
We render our sincere thanks to Prof. Suliman Mohamed Abdallah Al-Humayed, Dean, College of Medicine and Dr. Misfer Bin Safer Al- Shahrani, Department of Obstetrics & Gynecology, College of Medicine for their support. I sincerely thank Dr. Mohamed Eajaz Ahmed Sharif from the Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia for his support in literature collection and student guidance.
| References|| |
Li M-D. Leptin and Beyond: An Odyssey to the Central Control of Body Weight. Yale J Biol Med. 2011; 84, 1-7.
Londraville RL, Macotela Y, Duff RJ, Easterling MR, Liu O, CrespiGen EJ. Comparative endocrinology of leptin: Assessing function in a phylogenetic context. Comp Endocrinol, 2015; 1: 146-157.
Chehab FF. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors The Journal of endocrinology, 2014; 223: T37-T48.
Mantzoros CS, Magkos F, Brinkoetter M, Sienkiewicz E, Dardeno TA, Kim S-Y, Hamnvik O-PR, Anastasia Koniaris. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab. 2011, 301: E567-E584.
Harris RBS. Direct and Indirect Effects of Leptin on Adipocyte Metabolism. Biochim Biophys Acta, 2013; 1842: 414-423.
Zhou Y, Rui L. Leptin signaling and leptin resistance. Front Med. 2013; 7: 207-222.
Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism, 2015; 64: 24-34.
Mouzaki A, Panagoulias I, Raptis G, Farri- Kostopoulou E. Cord Blood Leptin Levels of Healthy Neonates Are Associated with IFN-γ Production by Cord Blood T-Cells PLoS One, 2012; 7: e40830.
Dardeno TA, Chou SH, Moon H-S, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in Human Physiology and Therapeutics. Front Neuroendocrinol. 2010; 31: 377-393.
Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism: clinical and experimental, 2015; 64: 24-34.
Tadokoro S, Ide S, Tokuyama R, Umeki H, Tatehara S, Kataoka S, Satomura K. Leptin Promotes Wound Healing in the Skin. PLoS One, 2015; 10: e0121242.
Aronis KN, Diakopoulos KN, Fiorenza CG, Chamberland JP, Mantzoros CS. Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans. Diabetologia, 2011; 54: 2358-2367.
Decker M, Martinez-Morentin L, Wang G, Lee Y, Liu Q, Leslie J, Ding L. Leptin-receptor-expressing bone marrow stromal cells are myofibroblasts in primary myelofibrosis. Nat Cell Biol, 2017; 19: 677-688.
Kumari P, Jaiswar SP, Shankhwar P, Deo S, Ahmad K, Iqbal B, Mahdi AA. Leptin as a Predictive Marker in Unexplained Infertility in North Indian Population. J Clin Diagn Res. 2017; 11: QC28-QC31.
Lacroix M, Battista MC, Doyon M, Moreau J, Patenaude J, Guillemette L, Ménard J, Ardilouze JL, Perron P, Hivert MF. Higher maternal leptin levels at second trimester are associated with subsequent greater gestational weight gain in late pregnancy. BMC Pregnancy Childbirth. 2016; 22: 16:62.
Lu Y, Hao X, Weng X. [Study on the relationships between leptin levels and weights of mothers and infants and the relationships of cord serum leptin to C-peptide, insulin and insulin like growth factor-II. Zhonghua Fu Chan Ke Za Zhi 2000; 35: 603-5.
Struwe E, Berzl GM, Schild RL, Dötsch J. Gene expression of placental hormones regulating energy balance in small for gestational age neonates. Eur J Obstet Gynecol Reprod Biol. 2009; 142: 38-42.
Smolinska N, Kaminski T, Siawrys G, Przala J. Long form of leptin receptor gene and protein expression in the porcine trophoblast and uterine tissues during early pregnancy and the oestrous cycle Anim Reprod Sci. 2009; 113: 125-36.
Hu C, Cao H, Pan X, Li J, He J, Pan Q, Xin J, Yu X, Li J, Wang Y, Zhu D, Li L. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology. Cell Death Dis 2018; 17: e2141.
Symonds ME, Bloor I, Ojha S, Budge H. The Placenta, Maternal Diet and Adipose Tissue Development in the Newborn. Ann Nutr Metab. 2017 Mar 17.
Mumtaz F, Memon AR, Yousfani S, Tahir SM, Khushk I, Memon M, Memon A. Role of serum leptin level as a marker of severity of pre eclampsia. J Ayub Med Coll Abbottabad. 2008; 20: 13-5.
Iciek R, Wender-Ozegowska E, Zawiejska A, Mikolajczak P, Mrozikiewicz PM, Pietryga M, Brazert J. Placental leptin and its receptor genes expression in pregnancies complicated by type 1 diabetes. J Physiol Pharmacol. 2013; 64: 579-85.
Petzel M, Stejskal D, Jedelsky L, Kadalova L, Safarcik K. The influence of estradiole and tibolone administration on leptin levels in women with surgically induced menopause. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008; 52: 101-5.
Eretová V, Haluzík M, Svobodová J, Zivný J. Serum levels of leptin and soluble leptin receptors in women after bilateral ovariectomy. Ceska GynekolJ, 2002; 67: 20-3.
Bedaiwy MA, Falcone T, Goldberg JM, Sharma RK, Nelson DR, Agarwal A. Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients. Hum Reprod. 2006; 21: 788-91.
Vadillo Buenfil M, Vela Ojeda J, Galindo Rodríguez G, Salazar Exaire D.Leptin and its influence on the main gynecoobstetric diseases. Ginecol ObstetMex. 2005; 73, 99-104.
Spicer LJ. Leptin: a possible metabolic signal affecting reproduction. Domest (2001) Anim Endocrinol. 2001; 21: 251-70.
Lobo LL, Kumar HU, Mishra T, Sundari T, Singh A, Kumar CV, Rao GK, Jahangir B, Misale V, Prashant P, Gajiwala NL, Thakkar AS. Small-for-gestational-age versus appropriate-for-gestational-age: Comparison of cord blood lipid profile & insulin levels in term newborns (SAGA-ACT study). Indian J Med Res 2016; 144: 194-199
Henson MC, Castracane VD. Leptin in pregnancy. Biol Reprod. 2000; 63: 1219-28.
Carlhäll S, Bladh M, Brynhildsen J, et al. Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: a prospective cohort study. BMC obesity. 2016; 3: 28.
[Figure 1], [Figure 2], [Figure 3]