title: Adiponectin Deficiency Leads to Female Subfertility and Ovarian Dysfunctions in Mice.
abstract: Adipose tissue plays an important role in regulating female fertility, owing to not only its energy stores but also the endocrine actions of secreted adipokines. As one of the adipokines, adiponectin is almost exclusively secreted from the fat, and its circulating concentration is paradoxically reduced in obesity. Although recent studies implied a purported positive role of adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed subfertility in female adiponectin null mice and therefore postulated a protective role of adiponectin in ovarian functions. Female adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes, disrupted estrous cycle, elevated number of atretic follicles, and impaired late folliculogenesis. Analysis of their sera revealed a significant decrease in estradiol and FSH but an increase in LH and testosterone at proestrus. In addition, we found marked reduction of progesterone levels at diestrus, a significant decrease in LH receptor expression as well as in the number of GnRH immunoreactive neurons. Adiponectin deficiency also altered the peak concentrations of LH surge and led to lower expression of Cytochrome P450 family 11 subfamily A member 1 (P450scc), an enzyme critical for progesterone synthesis, as well as an increase in BCL2 associated X, apoptosis regulator and Insulin like growth factor binding protein 4 in atretic follicles. These physiological and molecular events were independent of insulin sensitivity. Thus, we have revealed a novel mechanism linking adiponectin and female fertility that entails regulation of reproductive hormone balance and ovarian follicle development.
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Pan
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Gaurab
authors.initials: G
authors.lastname: Roy
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Allan
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Collaborative Innovation Center for Cancer Medicine (L.C., A.Z., F.L.), Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong 511495, China; Xiamen Medical College (L.C.), Xiamen, Fujian 361023, China; Department of Pathology (H.S.), Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, China; Department of Pathology (Yan Jin), Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; Center of Metabolic Disease Research (X.L., J.P., Y.La., Y.Li.), Nanjing Medical University, Nanjing, Jiangsu 211166, China; and School of Bioscience and Bioengineering (YaJ., G.R.), South China University of Technology, Guangzhou, Guangdong 510006, China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Li
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007247:Infertility, Female / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D013739:Testosterone / Q000097:blood
chemical_list: D052242:Adiponectin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone