Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 2953 2023-08-21 02:56:23 |
2 update references and layout Meta information modification 2953 2023-08-21 05:48:31 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Gruber, B.L.M.; Dolinsky, V.W. Adiponectin during Pregnancy and Gestational Diabetes. Encyclopedia. Available online: (accessed on 23 June 2024).
Gruber BLM, Dolinsky VW. Adiponectin during Pregnancy and Gestational Diabetes. Encyclopedia. Available at: Accessed June 23, 2024.
Gruber, Brittany L. Moyce, Vernon W. Dolinsky. "Adiponectin during Pregnancy and Gestational Diabetes" Encyclopedia, (accessed June 23, 2024).
Gruber, B.L.M., & Dolinsky, V.W. (2023, August 21). Adiponectin during Pregnancy and Gestational Diabetes. In Encyclopedia.
Gruber, Brittany L. Moyce and Vernon W. Dolinsky. "Adiponectin during Pregnancy and Gestational Diabetes." Encyclopedia. Web. 21 August, 2023.
Adiponectin during Pregnancy and Gestational Diabetes

Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. Pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM.

adiponectin pregnancy gestational diabetes

1. Metabolic Adaptations during Pregnancy

In mammals, several adaptations are required to sustain pregnancy. For instance, the maternal system exhibits increased blood volume and cardiac output accompanied by a corresponding increase in renal activity [1]. In addition, increased respiratory capacity and neurological changes, specifically increased neural plasticity and increased neurogenesis also occur during pregnancy and lactation [1][2]. Furthermore, metabolic adaptations are a necessary response to the changing metabolic demands of the mother and fetus (Figure 1). These can be broadly divided into two phases. In the first phase, which corresponds to the first two trimesters in a human pregnancy, there is an overall anabolic period. During this stage, the maternal system builds up energy stores, increasing lipid storage in tissues to prepare for increased breakdown and use later in pregnancy [3][4]. To achieve this, maternal energy consumption increases, as does de novo hepatic lipogenesis. In the later stages of pregnancy, lipid deposits are preferentially broken down for fatty acid oxidation, which spares glucose for fetal growth [3][4][5][6].
Figure 1. Metabolic adaptations of late gestation and the impact of gestational diabetes. ↑ increased, ↓ decreased.
Many hormonal, metabolic and immunological changes, including insulin resistance, are set in motion to adequately adapt to maternal and fetal needs during gestation (reviewed in [7][8][9]). Hormones such as human placental growth hormone (hPGH) increase progressively throughout pregnancy [10] and reduce signalling through the insulin receptor substrate–1(IRS-1), as well as glucose transporter (GLUT)-4 mediated glucose uptake. Later in gestation, maternal metabolism shifts to a catabolic phase and lipids are transiently increased, and mild hyperinsulinemia occurs. Despite these changes, in most pregnancies, normoglycemia is maintained and, in some cases, decreases, which could be due to the dilution effect as blood volume increases in the maternal system [11]. Additionally, increased insulin production and secretion by the maternal pancreas contribute to the maintenance of maternal glycemia [12]. In pregnancy, peripheral tissues become more insulin-resistant [3][13], and hepatic glucose output is not suppressed by insulin. In order to achieve glucose homeostasis in a healthy pregnancy, circulating insulin is increased to overcome insulin resistance [4]. Postnatally, these hormonal and metabolic changes return to baseline [14].
Changes to circulating hormones and cytokines in pregnancy impact insulin tolerance of peripheral tissues and compensatory adaptations of pancreatic β-cells that include increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion (GSIS) [15]. In the third trimester, progesterone increases and may have a role in increasing adipose tissue lipolysis and decreasing insulin sensitivity and glucose uptake in peripheral tissues, including adipose tissue [16][17]. Increased lipolysis from adipose tissue may lead to increased fatty acid uptake by the liver and reduced hepatic insulin sensitivity. Human placental growth hormone (hPGH) increases significantly throughout gestation and has a role in stimulating pregnancy-induced β-cell adaptations [18][19]. Prolactin (PrL) and placental lactogen (PL) have been implicated in pregnancy-associated β-cell adaptations [20], as well as in peripheral insulin resistance and increased lipolysis [21]. Tumour necrosis factor (TNF)-α increases in the circulation towards the end of pregnancy and has been shown to mediate the insulin resistance that occurs in the third trimester of pregnancy [22][23]. In GDM, more severe insulin resistance occurs, as well as increased inflammation and lipotoxicity, which lead to impairments in the necessary adaptations by pancreatic β cells [15]. Additionally, impaired insulin sensitivity in the liver leads to increased hepatic glucose output and reduced β oxidation. Lipid spillover from adipose tissue because of impaired expandability can lead to hepatic fat deposition and lipotoxicity in both the pancreas and the liver [24][25].

1.1. The Endocrine Pancreas and Its Adaptation to Pregnancy

Islet architecture varies between species, but mice and rats have relatively well-defined pancreatic islet structures, with abundant β-cells (in mice, making up 60–80% of cells in the islet) and scarcer polypeptide (PP) cells, δ-cells and α-cells [26][27][28]. Studies in human and animal models have provided evidence for plasticity of the pancreatic islet during pregnancy [12][27][29], which allows for increases in mass and hormone secretory capacity to compensate for the metabolic demands of pregnancy. This research has largely focused on β-cells and, to a lesser extent, α-cells due to their role in the management of blood glucose levels.
The pancreatic islet responds to the demands of pregnancy involving a range of adaptive mechanisms, including β-cell hyperplasia and hyper-functionality, that are driven by transcription factors and cell cycle regulators [15][30][31][32]. Pregnancy-induced β-cell expansion is achieved by proliferation, hypertrophic expansion and possibly neogenesis from progenitor cells; these mechanisms are accompanied by a temporary reduction in apoptosis [12][30][33] that has also been observed in islets during human pregnancy [12]. These changes may be mediated by crosstalk between increased placental signalling, the maternal pancreas and peripheral tissues, which have been illustrated by the use of animal models [34][35][36]. While some adaptive mechanisms are conserved between species, there are variations in the primary adaptive responses between rodent and human islets in pregnancy. For instance, in rodent models of pregnancy, neogenesis may only contribute a small amount to the expansion of β-cell mass, with proliferation playing a more significant role [37]. In human pregnancy, neogenesis may exceed proliferation as an adaptive mechanism [33][38]. However, human islets isolated during pregnancy are scarce, and samples were heterogenous in origin (from pregnancies of varying gestational length, maternal ages, ethnicities and causes of death), complicating the interpretation [12]. Despite the heterogeneity of available samples, human islets isolated during pregnancy show increases in β-cell area relative to non-pregnant controls [12][29].
In mice, pregnancy also increases alpha-cell mass, pancreatic glucagon-like peptide (GLP-1), and pancreatic and circulating glucagon levels [39] in association with a transient increase in serum glucagon, which was previously reported in human pregnancy [40]. Additionally, pregnant mice lacking α-cells were reported to exhibit impaired glucose tolerance, which was rescued by administration of glucagon-like peptide (GLP)-1 receptor agonists [39], illustrating a role of α-cells in insulin secretion and islet adaptation to pregnancy. Hormones secreted by cells adjacent to β-cells provide an additional layer of control over insulin secretion [41], which is only beginning to be explored in pregnancy.

1.2. White Adipose Tissue in Pregnancy

Maternal white adipose tissue (WAT) undergoes expansion during early pregnancy, providing energy stores of fat as fuel for later stages of pregnancy. High levels of insulin increase de novo lipogenesis, suppress adipose tissue lipolysis [7][42] and lower circulating free fatty acids [43]. Because a significant amount of glucose is utilized during the early stages of pregnancy, insulin increases glucose transport from serum and increases glycolysis. There is also evidence that crosstalk with the placenta during pregnancy may promote adipose tissue expansion [44]. Previously, it was found that during pregnancy, increased plasma protein A (PAPP-A) stimulates proteolysis of insulin-like growth factor (IGF)-binding protein-5, which releases IGF-1 and promotes adipose tissue expansion and proliferation to enable energy storage and prevent excess ectopic lipid deposition elsewhere in the body [45]. A follow-up study in mice showed that a lack of PAPP-A impaired adipose tissue expansion, pregnancy-induced insulin resistance and ectopic fat deposition in the form of hepatic steatosis—all factors that are associated with a GDM phenotype [46]. Expansion of adipose tissue can be achieved through hypertrophic adipocytes (to accommodate larger lipid droplets) or hyperplasia, which is the production of new adipocytes from precursors [45]. However, all forms of adipose tissue expansion are not equal; hyperplasia is linked to better glucose control, whereas hypertrophy is associated with more severe insulin resistance and is more prone to inflammation [47].
As pregnancy progresses, maternal glucose utilization is reduced, and maternal metabolism shifts into a catabolic phase, during which adipose tissue energy stores are broken down [43][48][49]. Steady increases in circulating free fatty acid (FFA) and glycerol, as well as decreases in adipocyte size and WAT mass, occur towards the end of gestation. During this phase of pregnancy, maternal metabolism relies more heavily on fatty acid oxidation for energetic needs, so the increased availability of lipids is an important physiological adaptation to late gestation. Indeed, hormonal changes associated with pregnancy, including circulating human placental lactogen (HPL) and increased TNF-α increase insulin resistance, thereby reducing the inhibitory effects of insulin on lipolysis [50].

1.3. Adaptations of Liver Metabolism during Pregnancy

The liver plays a significant role in maintaining maternal glucose homeostasis throughout gestation. Alterations in hepatic insulin signalling control these processes. In early pregnancy, when the metabolic demands of fetal growth are low, hepatic insulin sensitivity remains high, hepatic gluconeogenesis is inhibited by insulin and glucose is utilized for maternal energy [7][51]. In late pregnancy, hepatic insulin signalling is attenuated, which suppresses glycolysis and dysregulates gluconeogenesis, thereby directing more glucose to fetal growth. At the same time, there is an increase in the amount of fatty acid taken up and undergoing β-oxidation by the maternal liver [51][52].

2. Gestational Diabetes Mellitus

While insulin resistance is a natural process that occurs during pregnancy, compensation by the endocrine pancreas and peripheral tissues maintain glucose homeostasis until parturition. GDM may develop when compensatory mechanisms are insufficient to overcome the insulin resistance of pregnancy, which is associated with excessive gestational weight gain or obesity that precedes pregnancy [53].
GDM is defined as the new onset of hyperglycemia and glucose intolerance mid-gestation. Worldwide, as many as one in seven pregnancies is affected by GDM [54]. Maternal obesity and advanced maternal age are risk factors for development of GDM [55][56]. As an increasing number of women are beginning pregnancies later in life and there are increasing numbers of obese or overweight women, there has been a corresponding rise in the incidence of GDM. The implications of GDM on maternal health include difficulties with pregnancy (such as pre-eclampsia), complications in labour and delivery and increased risk of postnatal maternal health complications [54][57][58]. Women who have had GDM are at higher risk of developing GDM during subsequent pregnancies, as well as of developing type 2 diabetes (T2D) later in life [59]. Diagnostic criteria can vary between health regions. Undiagnosed GDM due to less stringent diagnostic criteria was associated with higher rates of complications such as excessive gestational weight gain, caesarean delivery, macrosomia and large-for-gestational-age (LGA) infants [60][61]. The only outcome-based guidelines are the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, which bases diagnosis on a fasting plasma glucose level exceeding 5.1 mmol/L or a plasma glucose level of 8.5 mmol/L 2 h after a 75 g oral glucose tolerance test [62]. Untreated GDM is associated with worse perinatal outcomes [63], and results from the Hyperglycemia and Adverse Pregnancy Outcomes study show more severe insulin resistance and glucose intolerance in offspring of mothers with untreated GDM [64]. Because the increased incidence of GDM reflects the metabolic health burden on women, clinical prevention strategies should target early preventive strategies for risk factors such as maternal obesity. The National Institute for Health and Care Excellence (NICE) prevention guidelines for pregnant women emphasize the importance of planning pregnancy and sharing information about diabetes outcomes and risks for mother and baby with women who are planning to conceive. In addition, the NICE guidelines recommend using the 75 g 2 h oral glucose tolerance test in all women with GDM risk factors in the first and second trimesters, offering continuous glucose monitoring to initiate earlier interventions [65].
During the COVID-19 pandemic, stakeholders and healthcare professionals were concerned about the increased exposure of pregnant women to infection. This resulted in a change in protocol for GDM screening in multiple countries, including in Canada, from a glucose challenge test to an A1C measurement and random, non-fasting blood glucose [66]. It was predicted that this strategy, despite limiting exposure of pregnant women to COVID-19, could potentially lead to missed GDM diagnosis, and a 2022 review of outcomes in Ireland, where similar changes were made, confirmed a significant decrease in GDM diagnoses compared to 2019 [67]. A 2020 review suggested that as many as 80% of GDM cases went undiagnosed in 2020 due to changes in diagnostic strategies during the COVID-19 pandemic [68]. Interestingly, cases of GDM overlooked due to alterations in screening strategies did not lead to worse maternal or fetal outcomes [67][68]. However, women diagnosed in 2020 were more likely to require insulin or metformin at the time of diagnosis and at term than those diagnosed as a result of screening prior to the pandemic [67]. The results of these changes to screening protocols suggest that glucose challenge and glucose tolerance tests are necessary to identify GDM in pregnancy.
The developmental origins of disease theory links in utero environmental exposures to chronic disease and adverse health outcomes later in the life of the offspring [69]. Given this critical stage of fetal development, it is not surprising that GDM also influences the health of the offspring. Data from epidemiological, birth cohort and animal model studies shows that diabetes during pregnancy is associated with the development of cardiometabolic diseases such as obesity, diabetes, high blood pressure, and renal and heart disease later in life [70][71][72][73][74][75][76][77]. For example, the HAPO follow-up study showed a linear relationship between higher maternal blood glucose and impaired glucose tolerance in 10–14-year-old offspring, independent of maternal and childhood BMI and family history of diabetes [78]. Glucose intolerance is also associated with leptin levels in five-year-old children [79]. These findings emphasize the necessity of earlier and more aggressive screening and treatment of GDM.

2.1. Impact of GDM on the Liver

Hepatic insulin resistance can contribute to more severe hyperglycemia during pregnancy, with dysregulation of hepatic gluconeogenesis resulting in excessive endogenous glucose production [6]. In addition, hyperlipidemia associated with maternal obesity and GDM can increase hepatic lipid synthesis and overload oxidative capacity, leading to secretion of very low-density lipoproteins (VLDL) with higher triacylglycerol content, as well as ectopic fat deposition in the liver [80]. The resultant lipotoxic and oxidative stress can exacerbate hepatic insulin resistance [81]. There are interesting links between the excessive storage of lipids in the liver, hepatic steatosis and GDM. The prevalence of non-alcoholic fatty liver disease (NAFLD) among women of childbearing age is estimated to be 10% [82]. Women with a history GDM are at higher risk of developing hepatic steatosis later in life [83]. Because hepatic steatosis contributes to insulin resistance, it is significant that development of fatty liver early in gestation (first trimester) can predict glucose intolerance mid-pregnancy [84] and precedes hyperglycemia in GDM [85]. Prospective cohort studies have shown that the presence of elevated visceral adipose tissue, together with sonographically detectable hepatic fat predicted GDM, independent of maternal age, ethnicity, and BMI [84][85]. The inclusion of NAFLD parameters such as hepatic steatosis and liver enzyme levels in an early prediction model for GDM improved the prediction of GDM development in women [86]. While GDM has been identified as a risk factor for the development of NAFLD [87], the mechanisms linking NAFLD to the development of GDM remain to be determined.

2.2. β-Cell Dysfunction in GDM

During pregnancy, β-cells must implement structural and functional changes to overcome insulin resistance and maintain normoglycemia. However, in a subset of women, functional and structural adaptations are impaired, contributing to GDM development. While the specific causes of impaired β-cell compensation in GDM continue to be investigated, this adaptive failure is likely multifactorial, involving genetic variants, nutrient overload and metabolic stress or increased inflammation [15][88][89]. Pancreatic β-cells have been shown to be affected by systemic inflammation [13]. Obese individuals and women with GDM have been found to have higher levels of circulating TNF-α, a proinflammatory cytokine linked to disrupted β-cell function and dedifferentiation [90][91]. Other markers of inflammation such as interleukin 1β (IL-1β) and interferon-γ (IFNγ) are reportedly increased under conditions of metabolic stress [92][93] and can trigger endoplasmic reticulum (ER) stress in β-cells, which prevents adaptation to insulin resistance during pregnancy, contributing to β-cell dysfunction [94].
Pancreatic β-cells are also susceptible to the effects of obesity and nutrient overload. Lipotoxicity and glucotoxicity are potential mechanisms involved in β-cell dysfunction in T2D and GDM [95]. Prolonged exposure to hyperglycemia can lead to impairments in β-cell function and reduced insulin secretion, which can become irreversible [96]. Exposure to high levels of lipids results in lipotoxic β-cell dysfunction [97]. ER stress [98] and oxidative stress [95] are triggered when lipids build up within the pancreatic islet and impair insulin production. Increased oxidative and ER stress can contribute to cell damage and β-cell apoptosis [95].

2.3. Impact of GDM on Adipose Tissue

In GDM, insulin resistance in WAT can result in excessive lipolysis, low-grade inflammation and dysregulated adipokine signalling [99]. While a degree of insulin resistance is a physiological adaptation in late gestation, in GDM, significant impairments can occur in downstream insulin signalling in WAT (e.g., decreased insulin receptor-β (IR-β) phosphorylation, downregulation of IRS1 and signalling through PI3K) [100]. Glucose uptake by adipose tissue is also blunted, with defects in GLUT4 translocation observed in GDM [51].
Insulin resistance in adipose tissue also impacts lipid metabolism, and impaired post-receptor signalling resulted in dramatically elevated WAT lipolysis in women with GDM [99]. Adipose tissue expansion is important to accommodate increased lipogenesis in early pregnancy. Without adequate WAT expansion, more severe insulin resistance and ectopic fat deposition in peripheral tissues, as well as adipose tissue inflammation occur [45]. Impairments in WAT expansion has been implicated in GDM [45]. In GDM, adipocytes become larger but show limited vascularization and reduced expression of markers associated with expandability. A proteomic study comparing adipose tissue isolated from women with GDM identified increases in fibrinogen and LUM, the former of which is associated with inflammation and the latter of which is an extracellular matrix protein, indicating adipose tissue rigidity and reduced flexibility [101]. Obesity in pregnancy is associated with increased insulin resistance, dyslipidemia, and inflammation [102]. This leads to a higher risk of endothelial dysfunction and lipotoxicity, worsening insulin resistance and metabolic dysfunction [103][104].


  1. Soma-Pillay, P.; Catherine, N.-P.; Tolppanen, H.; Mebazaa, A.; Tolppanen, H.; Mebazaa, A. Physiological changes in pregnancy. Cardiovasc. J. Afr. 2016, 27, 89–94.
  2. Hillerer, K.M.; Jacobs, V.R.; Fischer, T.; Aigner, L. The Maternal Brain: An Organ with Peripartal Plasticity. Neural Plast. 2014, 2014, 574159.
  3. Vivas, Y.; Diez-Hochleitner, M.; Izquierdo-Lahuerta, A.; Corrales, P.; Horrillo, D.; Velasco, I.; Martinez-Garcia, C.; Campbell, M.; Sevillano, J.; Ricote, M.; et al. Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations. Mol. Med. 2016, 22, 724–736.
  4. Wharfe, M.D.; Wyrwoll, C.; Waddell, B.J.; Mark, P.J. Pregnancy-induced changes in the circadian expression of hepatic clock genes: Implications for maternal glucose homeostasis. Am. J. Physiol. Metab. 2016, 311, E575–E586.
  5. Elliott, J.A. The effect of pregnancy on the control of lipolysis in fat cells isolated from human adipose tissue. Eur. J. Clin. Investig. 1975, 5, 159–163.
  6. Butte, N.F. Carbohydrate and lipid metabolism in pregnancy: Normal compared with gestational diabetes mellitus. Am. J. Clin. Nutr. 2000, 71, 1256S–1261S.
  7. Zeng, Z.; Liu, F.; Li, S. Metabolic Adaptations in Pregnancy: A Review. Ann. Nutr. Metab. 2017, 70, 59–65.
  8. Herrera, E. Lipid Metabolism in Pregnancy and its Consequences in the Fetus and Newborn. Endocrine 2002, 19, 43–56.
  9. Parrettini, S.; Caroli, A.; Torlone, E. Nutrition and Metabolic Adaptations in Physiological and Complicated Pregnancy: Focus on Obesity and Gestational Diabetes. Front. Endocrinol. 2020, 11, 611929.
  10. Handwerger, S.; Freemark, M. The Roles of Placental Growth Hormone and Placental Lactogen in the Regulation of Human Fetal Growth and Development. J. Pediatr. Endocrinol. Metab. 2000, 13, 343–356.
  11. Angueira, A.R.; Ludvik, A.E.; Reddy, T.E.; Wicksteed, B.; Lowe, W.L., Jr.; Layden, B.T. New Insights Into Gestational Glucose Metabolism: Lessons Learned From 21st Century Approaches. Diabetes 2015, 64, 327–334.
  12. Butler, A.E.; Cao-Minh, L.; Galasso, R.; Rizza, R.A.; Corradin, A.; Cobelli, C.; Butler, P.C. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 2010, 53, 2167–2176.
  13. Chen, L.; Chen, R.; Wang, H.; Liang, F. Mechanisms Linking Inflammation to Insulin Resistance. Int. J. Endocrinol. 2015, 2015, 508409.
  14. Kirwan, J.P.; Varastehpour, A.; Jing, M.; Presley, L.; Shao, J.; Friedman, J.E.; Catalano, P.M. Reversal of Insulin Resistance Postpartum Is Linked to Enhanced Skeletal Muscle Insulin Signaling. J. Clin. Endocrinol. Metab. 2004, 89, 4678–4684.
  15. Moyce, B.L.; Dolinsky, V.W. Maternal beta-cell adaptations in pregnancy and placental signalling: Implications for gestational diabetes. Int. J. Mol. Sci. 2018, 19, 3467.
  16. Kalkhoff, R.K. Metabolic effects of progesterone. Am. J. Obstet. Gynecol. 1982, 142, 735–738.
  17. Lacasa, D.; Le Liepvre, X.; Ferre, P.; Dugail, I. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue. J. Biol. Chem. 2001, 276, 11512–11516.
  18. Nielsen, J.H. Beta cell adaptation in pregnancy: A tribute to Claes Hellerström. Upsala J. Med. Sci. 2016, 121, 151–154.
  19. Nielsen, J.H.; Galsgaard, E.D.; Møldrup, A.; Friedrichsen, B.N.; Billestrup, N.; Hansen, J.A.; Lee, Y.C.; Carlsson, C. Regulation of beta-cell mass by hormones and growth factors. Diabetes 2001, 50 (Suppl. S1), S25.
  20. Billestrup, N.; Nielsen, J.H. The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I. Endocrinology 1991, 129, 883–888.
  21. Williams, C.; Coltart, T.M. Adipose tissue metabolism in pregnancy: The lipolytic effect of human placental lactogen. Br. J. Obstet. Gynaecol. 1978, 85, 43–46.
  22. Xu, J.; Zhao, Y.H.; Chen, Y.P.; Yuan, X.L.; Wang, J.; Zhu, H.; Lu, C.M. Maternal Circulating Concentrations of Tumor Necrosis Factor-Alpha, Leptin, and Adiponectin in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis. Sci. World J. 2014, 2014, 926932.
  23. Wei, W.; Zhang, X. Expression of ADP and TNF-α in patients with gestational diabetes mellitus and its relationship with pregnancy outcomes. Exp. Ther. Med. 2020, 20, 2184–2190.
  24. Oh, Y.S.; Bae, G.D.; Baek, D.J.; Park, E.Y.; Jun, H.S. Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes. Front. Endocrinol. 2018, 9, 384.
  25. Azzu, V.; Vacca, M.; Virtue, S.; Allison, M.; Vidal-Puig, A. Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease. Gastroenterology 2020, 158, 1899–1912.
  26. Baetens, D.; Malaisse-Lagae, F.; Perrelet, A.; Orci, L. Endocrine Pancreas: Three-Dimensional Reconstruction Shows Two Types of Islets of Langerhans. Science 1979, 206, 1323–1325.
  27. Kim, A.; Miller, K.; Jo, J.; Kilimnik, G.; Wojcik, P.; Hara, M. Islet architecture: A comparative study. Islets 2009, 1, 129–136.
  28. Wieczorek, G.; Pospischil, A.; Perentes, E. A comparative immunohistochemical study of pancreatic islets in laboratory animals (rats, dogs, minipigs, nonhuman primates). Exp. Toxicol. Pathol. 1998, 50, 151–172.
  29. Van Assche, F.A.; Aerts, L.; De Prins, F. A morphological study of the endocrine pancreas in human pregnancy. BJOG Int. J. Obstet. Gynaecol. 1978, 85, 818–820.
  30. Ernst, S.; Demirci, C.; Valle, S.; Velazquez-Garcia, S.; Garcia-Ocaña, A. Mechanisms in the adaptation of maternal β-cells during pregnancy. Diabetes Manag. 2011, 1, 239–248.
  31. Sferruzzi-Perri, A.N.; Vaughan, O.R.; Haro, M.; Cooper, W.N.; Musial, B.; Charalambous, M.; Pestana, D.; Ayyar, S.; Ferguson-Smith, A.C.; Burton, G.J.; et al. An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J. 2013, 27, 3928–3937.
  32. Zhang, Z.; Piro, A.L.; Dai, F.F.; Wheeler, M.B. Adaptive Changes in Glucose Homeostasis and Islet Function During Pregnancy: A Targeted Metabolomics Study in Mice. Front. Endocrinol. 2022, 13, 852149.
  33. Bonner-Weir, S.; Guo, L.; Li, W.-C.; Ouziel-Yahalom, L.; Weir, G.C.; Sharma, A. Islet Neogenesis: A Possible Pathway for Beta-Cell Replenishment. Rev. Diabet. Stud. 2012, 9, 407–416.
  34. Aye, I.L.; Powell, T.L.; Jansson, T. Review: Adiponectin--the missing link between maternal adiposity, placental transport and fetal growth? Placenta 2013, 34, S40–S45.
  35. Rawn, S.M.; Huang, C.; Hughes, M.; Shaykhutdinov, R.; Vogel, H.J.; Cross, J.C. Pregnancy Hyperglycemia in Prolactin Receptor Mutant, but Not Prolactin Mutant, Mice and Feeding-Responsive Regulation of Placental Lactogen Genes Implies Placental Control of Maternal Glucose Homeostasis1. Biol. Reprod. 2015, 93, 75.
  36. Vasavada, R.C.; Garcia-Ocaña, A.; Zawalich, W.S.; Sorenson, R.L.; Dann, P.; Syed, M.; Ogren, L.; Talamantes, F.; Stewart, A.F. Targeted Expression of Placental Lactogen in the Beta Cells of Transgenic Mice Results in Beta Cell Proliferation, Islet Mass Augmentation, and Hypoglycemia. J. Biol. Chem. 2000, 275, 15399–15406.
  37. Rieck, S.; Kaestner, K.H. Expansion of β-cell mass in response to pregnancy. Trends Endocrinol. Metab. 2010, 21, 151–158.
  38. Søstrup, B.; Gaarn, L.W.; Nalla, A.; Billestrup, N.; Nielsen, J.H. Co-ordinated regulation of neurogenin-3 expression in the maternal and fetal pancreas during pregnancy. Acta Obstet. Gynecol. Scand. 2014, 93, 1190–1197.
  39. Qiao, L.; Saget, S.; Lu, C.; Zang, T.; Dzyuba, B.; Hay, J.W.W.; Shao, J. The Essential Role of Pancreatic α-Cells in Maternal Metabolic Adaptation to Pregnancy. Diabetes 2022, 71, 978–988.
  40. Luyckx, A.S.; Gerard, J.; Gaspard, U.; Lefebvre, P.J. Plasma glucagon levels in normal women during pregnancy. Diabetologia 1975, 11, 549–554.
  41. Morriseau, T.S.; Doucette, C.A.; Dolinsky, V.W. More than meets the islet: Aligning nutrient and paracrine inputs with hormone secretion in health and disease. Am. J. Physiol. Metab. 2022, 322, E446–E463.
  42. Coltart, T.M.; Williams, C. Effect of insulin on adipose tissue lipolysis in human pregnancy. BJOG Int. J. Obstet. Gynaecol. 1976, 83, 241–244.
  43. Pujol, E.; Proenza, A.; Llado, I.; Roca, P. Pregnancy effects on rat adipose tissue lipolytic capacity are dependent on anatomical location. Cell. Physiol. Biochem. 2005, 16, 229–236.
  44. Jayabalan, N.; Nair, S.; Nuzhat, Z.; Rice, G.E.; Zuñiga, F.A.; Sobrevia, L.; Leiva, A.; Sanhueza, C.; Gutiérrez, J.A.; Lappas, M.; et al. Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes Mellitus Pregnancies via Exosomes. Front. Endocrinol. 2017, 8, 239.
  45. Rojas-Rodriguez, R.; Lifshitz, L.M.; Bellvé, K.D.; Min, S.Y.; Pires, J.; Leung, K.; Boeras, C.; Sert, A.; Draper, J.T.; Corvera, S.; et al. Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus. Diabetologia 2015, 58, 2106–2114.
  46. Rojas-Rodriguez, R.; Ziegler, R.; DeSouza, T.; Majid, S.; Madore, A.S.; Amir, N.; Pace, V.A.; Nachreiner, D.; Alfego, D.; Mathew, J.; et al. PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans. Sci. Transl. Med. 2020, 12, eaay4145.
  47. Hoffstedt, J.; Arner, E.; Wahrenberg, H.; Andersson, D.P.; Qvisth, V.; Löfgren, P.; Rydén, M.; Thörne, A.; Wirén, M.; Palmér, M.; et al. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia 2010, 53, 2496–2503.
  48. Knopp, R.H.; Herrera, E.; Freinkel, N. Carbohydrate metabolism in pregnancy. 8. Metabolism of adipose tissue isolated from fed and fasted pregnant rats during late gestation. J. Clin. Investig. 1970, 49, 1438–1446.
  49. Palacín, M.; Lasunción, M.A.; Asunción, M.; Herrera, E. Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat. Metab. Clin. Exp. 1991, 40, 534–539.
  50. Kirwan, J.P.; Hauguel-De Mouzon, S.; Lepercq, J.; Challier, J.-C.; Huston-Presley, L.; Friedman, J.E.; Kalhan, S.C.; Catalano, P.M. TNF-alpha Is a Predictor of Insulin Resistance in Human Pregnancy. Diabetes 2002, 51, 2207–2213.
  51. Lain, K.Y.; Catalano, P.M. Metabolic changes in pregnancy. Clin. Obstet. Gynecol. 2007, 50, 938–948.
  52. Towler, M.C.; Hardie, D.G. AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling. Circ. Res. 2007, 100, 328–341.
  53. Plows, J.F.; Stanley, J.L.; Baker, P.N.; Reynolds, C.M.; Vickers, M.H. The Pathophysiology of Gestational Diabetes Mellitus. Int. J. Mol. Sci. 2018, 19, 3342.
  54. Guariguata, L.; Linnenkamp, U.; Beagley, J.; Whiting, D.; Cho, N. Global estimates of the prevalence of hyperglycaemia in pregnancy. Diabetes Res. Clin. Pract. 2014, 103, 176–185.
  55. Brown, J.; Alwan, N.A.; West, J.; Brown, S.; McKinlay, C.J.; Farrar, D.; Crowther, C.A. Lifestyle interventions for the treatment of women with gestational diabetes. Cochrane Database Syst. Rev. 2017, 2017, CD011970.
  56. Hui, A.L.; Sevenhuysen, G.; Harvey, D.; Salamon, E. Barriers and coping strategies of women with gestational diabetes to follow dietary advice. Women Birth 2014, 27, 292–297.
  57. Buchanan, T.A.; Xiang, A.; Page, K.A. Gestational diabetes mellitus: Risks and management during and after pregnancy. Nat. Rev. Endocrinol. 2012, 8, 639–649.
  58. Sherifali, D.; Rabi, D.M.; McDonald, C.G.; Butalia, S.; Campbell, D.J.T.; Hunt, D.; Leung, A.A.; Mahon, J.; McBrien, K.A.; Palda, V.A.; et al. Methods. Can. J. Diabetes 2018, 42, S6–S9.
  59. Herath, H.; Herath, R.; Wickremasinghe, R. Gestational diabetes mellitus and risk of type 2 diabetes 10 years after the index pregnancy in Sri Lankan women—A community based retrospective cohort study. PLoS ONE 2017, 12, e0179647.
  60. Meek, C.L.; Lewis, H.B.; Patient, C.; Murphy, H.R.; Simmons, D. Diagnosis of gestational diabetes mellitus: Falling through the net. Diabetologia 2015, 58, 2003–2012.
  61. Hung, T.-H.; Hsieh, T.-T. The Effects of Implementing the International Association of Diabetes and Pregnancy Study Groups Criteria for Diagnosing Gestational Diabetes on Maternal and Neonatal Outcomes. PLoS ONE 2015, 10, e0122261.
  62. Rani, P.R.; Begum, J. Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. J. Clin. Diagn. Res. 2016, 10, QE01–QE04.
  63. Shah, B.R.; Sharifi, F. Perinatal outcomes for untreated women with gestational diabetes by IADPSG criteria: A population-based study. BJOG Int. J. Obstet. Gynaecol. 2020, 127, 116–122.
  64. Lowe, W.L., Jr.; Scholtens, D.M.; Kuang, A.; Linder, B.; Lawrence, J.M.; Lebenthal, Y.; McCance, D.; Hamilton, J.; Nodzenski, M.; Talbot, O.; et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care 2019, 42, 372–380.
  65. Murphy, H.R. 2020 NICE guideline update: Good news for pregnant women with type 1 diabetes and past or current gestational diabetes. Diabet. Med. 2021, 38, e14576.
  66. Yamamoto, J.M.; Donovan, L.E.; Feig, D.S.; Berger, H. Urgent Update—Temporary Alternative Screening Strategy for Gestational Diabetes Screening During the COVID-19 Pandemic. Can. J. Diabetes 2022, 65, 37–54.
  67. Keating, N.; Carpenter, K.; McCarthy, K.; Coveney, C.; McAuliffe, F.; Mahony, R.; Walsh, J.; Hatunic, M.; Higgins, M. Clinical Outcomes Following a Change in Gestational Diabetes Mellitus Diagnostic Criteria Due to the COVID-19 Pandemic: A Case-Control Study. Int. J. Environ. Res. Public Health 2022, 19, 1884.
  68. McIntyre, H.D.; Gibbons, K.; Ma, R.C.; Tam, W.H.; Sacks, D.A.; Lowe, J.; Madsen, L.R.; Catalano, P.M. Testing for gestational diabetes during the COVID-19 pandemic. An evaluation of proposed protocols for the United Kingdom, Canada and Australia. Diabetes Res. Clin. Pract. 2020, 167, 108353.
  69. Agarwal, P.; Morriseau, T.S.; Kereliuk, S.M.; Doucette, C.A.; Wicklow, B.A.; Dolinsky, V.W. Maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring. Crit. Rev. Clin. Lab. Sci. 2018, 55, 71–101.
  70. Guillemette, L.; Wicklow, B.; Sellers, E.A.; Dart, A.; Shen, G.X.; Dolinsky, V.W.; Gordon, J.W.; Jassal, D.S.; Nickel, N.; Duhamel, T.A.; et al. Intrauterine exposure to diabetes and risk of cardiovascular disease in adolescence and early adulthood: A population-based birth cohort study. Can. Med. Assoc. J. 2020, 192, E1104–E1113.
  71. Franks, P.W.; Looker, H.C.; Kobes, S.; Touger, L.; Tataranni, P.A.; Hanson, R.L.; Knowler, W.C. Gestational Glucose Tolerance and Risk of Type 2 Diabetes in Young Pima Indian Offspring. Diabetes 2006, 55, 460–465.
  72. Sellers, E.A.; Dean, H.J.; Shafer, L.A.; Martens, P.J.; Phillips-Beck, W.; Heaman, M.; Prior, H.J.; Dart, A.B.; McGavock, J.; Morris, M.; et al. Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non–First Nations Offspring. Diabetes Care 2016, 39, 2240–2246.
  73. Dabelea, D.; Hanson, R.L.; Lindsay, R.S.; Pettitt, D.J.; Imperatore, G.; Gabir, M.M.; Roumain, J.; Bennett, P.H.; Knowler, W.C. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: A study of discordant sibships. Diabetes 2000, 49, 2208–2211.
  74. Dart, A.B.; Ruth, C.A.; Sellers, E.A.; Au, W.; Dean, H.J. Maternal Diabetes Mellitus and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in the Child. Am. J. Kidney Dis. 2015, 65, 684–691.
  75. Do, V.; Eckersley, L.; Lin, L.; Davidge, S.T.; Stickland, M.K.; Ojala, T.; Serrano-Lomelin, J.; Hornberger, L.K. Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers. CJC Open 2021, 3, 345–353.
  76. Yu, Y.; Arah, O.A.; Liew, Z.; Cnattingius, S.; Olsen, J.; Sorensen, H.T.; Qin, G.; Li, J. Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: Population based cohort study with 40 years of follow-up. BMJ 2019, 367, l6398.
  77. Yu, Y.; Soohoo, M.; Sørensen, H.T.; Li, J.; Arah, O.A. Gestational Diabetes Mellitus and the Risks of Overall and Type-Specific Cardiovascular Diseases: A Population- and Sibling-Matched Cohort Study. Diabetes Care 2022, 45, 151–159.
  78. Scholtens, D.M.; Kuang, A.; Lowe, L.P.; Hamilton, J.; Lawrence, J.M.; Lebenthal, Y.; Brickman, W.J.; Clayton, P.; Ma, R.C.; McCance, D.; et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care 2019, 42, 381–392.
  79. Blais, K.; Arguin, M.; Allard, C.; Doyon, M.; Dolinsky, V.W.; Bouchard, L.; Hivert, M.F.; Perron, P. Maternal glucose in pregnancy is associated with child’s adiposity and leptin at 5 years of age. Pediatr. Obes. 2021, 16, e12788.
  80. White, S.L.; on behalf of the UPBEAT Consortium; Pasupathy, D.; Sattar, N.; Nelson, S.M.; Lawlor, D.A.; Briley, A.L.; Seed, P.T.; Welsh, P.; Poston, L. Metabolic profiling of gestational diabetes in obese women during pregnancy. Diabetologia 2017, 60, 1903–1912.
  81. Choi, S.S.; Diehl, A.M. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr. Opin. Lipidol. 2008, 19, 295–300.
  82. Hershman, M.; Mei, R.; Kushner, T. Implications of Nonalcoholic Fatty Liver Disease on Pregnancy and Maternal and Child Outcomes. Gastroenterol. Hepatol. 2019, 15, 221–228.
  83. Lavrentaki, A.; Thomas, T.; Subramanian, A.; Valsamakis, G.; Thomas, N.; Toulis, K.A.; Wang, J.; Daly, B.; Saravanan, P.; Sumilo, D.; et al. Increased risk of non-alcoholic fatty liver disease in women with gestational diabetes mellitus: A population-based cohort study, systematic review and meta-analysis. J. Diabetes Its Complicat. 2019, 33, 107401.
  84. De Souza, L.R.; Berger, H.; Retnakaran, R.; Vlachou, P.A.; Maguire, J.L.; Nathens, A.B.; Connelly, P.W.; Ray, J.G. Hepatic fat and abdominal adiposity in early pregnancy together predict impaired glucose homeostasis in mid-pregnancy. Nutr. Diabetes 2016, 6, e229.
  85. Lee, S.M.; Kwak, S.H.; Koo, J.N.; Oh, I.H.; Kwon, J.E.; Kim, B.J.; Kim, S.M.; Kim, S.Y.; Kim, G.M.; Joo, S.K.; et al. Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus. Diabetologia 2019, 62, 238–248.
  86. Lee, S.M.; Hwangbo, S.; Norwitz, E.R.; Koo, J.N.; Oh, I.H.; Choi, E.S.; Jung, Y.M.; Kim, S.M.; Kim, B.J.; Kim, S.Y.; et al. Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods. Clin. Mol. Hepatol. 2022, 28, 105–116.
  87. Ajmera, V.H.; Gunderson, E.P.; VanWagner, L.B.; Lewis, C.E.; Carr, J.J.; Terrault, N.A. Gestational Diabetes Mellitus Is Strongly Associated with Non-Alcoholic Fatty Liver Disease. Am. J. Gastroenterol. 2016, 111, 658–664.
  88. Agarwal, P.; Brar, N.; Morriseau, T.S.; Kereliuk, S.M.; Fonseca, M.A.; Cole, L.K.; Jha, A.; Xiang, B.; Hunt, K.L.; Seshadri, N.; et al. Gestational Diabetes Adversely Affects Pancreatic Islet Architecture and Function in the Male Rat Offspring. Endocrinology 2019, 160, 1907–1925.
  89. Lorenzo, P.I.; Martín-Montalvo, A.; Vuilleumier, N.C.; Gauthier, B.R. Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus. Int. J. Mol. Sci. 2019, 20, 6171.
  90. Nordmann, T.M.; Dror, E.; Schulze, F.; Traub, S.; Berishvili, E.; Barbieux, C.; Böni-Schnetzler, M.; Donath, M.Y. The Role of Inflammation in β-cell Dedifferentiation. Sci. Rep. 2017, 7, 6285.
  91. Yang, Y.; Liu, L.; Liu, B.; Li, Q.; Wang, Z.; Fan, S.; Wang, L. Functional Defects of Regulatory T Cell Through Interleukin 10 Mediated Mechanism in the Induction of Gestational Diabetes Mellitus. DNA Cell Biol. 2018, 37, 278–285.
  92. Boyle, K.E.; Newsom, S.; Janssen, R.C.; Lappas, M.; Friedman, J.E. Skeletal muscle MnSOD, mitochondrial complex II, and SIRT3 enzyme activities are decreased in maternal obesity during human pregnancy and gestational diabetes mellitus. J. Clin. Endocrinol. Metab. 2013, 98, E1601–E1609.
  93. Liong, S.; Lappas, M. Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women. Mol. Cell. Endocrinol. 2016, 425, 11–25.
  94. Ehses, J.A.; Perren, A.; Eppler, E.; Ribaux, P.; Pospisilik, J.A.; Maor-Cahn, R.; Gueripel, X.; Ellingsgaard, H.; Schneider, M.K.J.; Biollaz, G.; et al. Increased Number of Islet-Associated Macrophages in Type 2 Diabetes. Diabetes 2007, 56, 2356–2370.
  95. Sharma, R.B.; Alonso, L.C. Lipotoxicity in the Pancreatic Beta Cell: Not Just Survival and Function, but Proliferation as Well? Curr. Diabetes Rep. 2014, 14, 492.
  96. Morán, A.; Zhang, H.J.; Olson, L.K.; Harmon, J.S.; Poitout, V.; Robertson, R.P. Differentiation of glucose toxicity from beta cell exhaustion during the evolution of defective insulin gene expression in the pancreatic islet cell line, HIT-T15. J. Clin. Investig. 1997, 99, 534–539.
  97. Unger, R.H. Lipotoxicity in the Pathogenesis of Obesity-Dependent NIDDM: Genetic and Clinical Implications. Diabetes 1995, 44, 863.
  98. Kitamura, Y.I.; Kitamura, T.; Kruse, J.-P.; Raum, J.C.; Stein, R.; Gu, W.; Accili, D. FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction. Cell Metab. 2005, 2, 153–163.
  99. Tumurbaatar, B.; Poole, A.; Olson, G.; Makhlouf, M.; Sallam, H.S.; Thukuntla, S.; Kankanala, S.; Ekhaese, O.; Gomez, G.; Chandalia, M.; et al. Adipose Tissue Insulin Resistance in Gestational Diabetes. Metab. Syndr. Relat. Disord. 2017, 15, 86–92.
  100. Sevillano, J.; De Castro, J.; Bocos, C.; Herrera, E.; Ramos-Alvarez, M.P. Role of Insulin Receptor Substrate-1 Serine 307 Phosphorylation and Adiponectin in Adipose Tissue Insulin Resistance in Late Pregnancy. Endocrinology 2007, 148, 5933–5942.
  101. Oliva, K.; Barker, G.; Rice, G.E.; Bailey, M.J.; Lappas, M. 2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue. J. Endocrinol. 2013, 218, 165–178.
  102. Catalano, P.A.; Ehrenberg, H. The short-and long-term implications of maternal obesity on the mother and her offspring. BJOG Int. J. Obstet. Gynaecol. 2006, 113, 1126–1133.
  103. Jarvie, E.; Hauguel-De-Mouzon, S.; Nelson, S.; Sattar, N.; Catalano, P.M.; Freeman, D.J. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring. Clin. Sci. 2010, 119, 123–129.
  104. Chen, X.; Scholl, T.O. Oxidative stress: Changes in pregnancy and with gestational diabetes mellitus. Curr. Diabetes Rep. 2005, 5, 282–288.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : ,
View Times: 230
Revisions: 2 times (View History)
Update Date: 21 Aug 2023
Video Production Service