Department of Obstetrics and Gynecology: Faculty Research and Presentations
The Department of Obstetrics and Gynecology at Augusta University
is a comprehensive clinical service and educational department,
specializing in the healthcare of women both on a primary and
referral basis. We provide quality clinical services in following
areas: General Obstetrics and Gynecology, Gynecologic Oncology,
Maternal-Fetal Medicine, Reproductive Endocrinology, Infertility,
and Genetics, and Urogynecology and Pelvic Surgery.
This collection contains the scholarly works of faculty in the Department of Obstetrics and Gynecology.
All items in the repository are protected by copyright; they may be used for educational purposes with proper attribution. All other uses require the author's permission.
The Function of NELF and ESR1 in Puberty Development and FertilityReproductive disorders affect 10-15% of the population in the United States and result in debilitating social and economic issues. Reproductive dysfunction may be displayed as delayed puberty or infertility due to defects in the hypothalamic-pituitary gonadal (HPG) axis. This axis is controlled by gonadotropin releasing hormone (GnRH) through the release of GnRH peptide. An important critical barrier to understanding normal puberty is the lack of known specific genes that regulate the development, migration and function of hypothalamic GnRH neurons, which synthesize and secrete GnRH neuropeptide in a pulsatile pattern into the portal blood. Several human diseases occur as the result of impaired GnRH function. Idiopathic hypogonadotropic hypogonadism (IHH) patients present with decreased gonadotropins and sex steroids leading to permanent delayed of puberty and infertility. Kallmann syndrome (KS) combines IHH phenotypes in addition to anosmia/hyposmia as there is impairment in migration o f GnRH neurons and olfactory neurons/axons. To date, the molecular basis has only been identified for approximately 40% o f all IHH/KS patients. The purpose of this study was to understand the role and function o f genes, such as NELF (nasal embryonic LHRH factor), in pubertal development and fertility. NELF, a nuclear protein isolated from migratory GnRH neurons, has been shown to be involved in the pathogenesis of IHH/KS, and knockdown impairs GnRH neuron migration in vitro. The mechanism o f NELF’s role relevant to GnRH migration/signaling and its effects on pubertal development and fertility are unclear. NELF function has been studied in GnRH cell lines, but not in the whole organism. The overall goals of this study are to characterize the phenotypic features of /Ve/^knockout (KO) mice, classify the prevalence of the different variants of NELF reported, and the inheritance patterns of IHH/KS genes including NELF, and finally examine the phenotype and hormonal profile o f an estrogen receptor-a (ESR1) mutation in a woman. Methods: Following breeding of heterozygous mice to generate homozygous N elf knockout mice, pubertal onset was assessed by daily monitoring of weight, vaginal opening (females), and anogenital distance (males). In addition we determined fertility of the mice by doing a continuous 90 day breeding study. Immunocytochemical labeling o f GnRH neurons was performed and analyzed for migration and count; hematoxylin and eosin stains were performed to visualize gonadal morphology. Three additional studies were also performed: 1) NELF splice variants were studied in immortalized human and mouse GnRH neurons; 2) the prevalence of digenic disease in IHH/KS was determined when the 13 most common genes were sequenced in 48 patients; and 3) the first woman with an estrogen receptor-a (ESR1) mutation was characterized clinically and by in vitro analysis. Results: Female NelfK O mice had delayed puberty, small uteri, and a decrease in GnRH neuron distribution distance, but male KO mice had normal puberty and GnRH neuron distribution distance. Both male and female KO mice had decreased litter size. Furthermore, NELF variant 2 was the dominant variant in both mouse and human GnRH neurons. Both nuclear and non-nuclear splice variants were expressed at the RNA and protein levels. DNA sequencing of 13 genes in 48 IHH/KS patients demonstrated that -90% of the cases are monogenic. Finally, the ESR1 mutation in the female patient led to absent pubertal development as ESR1 signaling is profoundly defective.
Maternal Health Literacy Progression Among Rural Perinatal WomenThis research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13-30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857-860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman's use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman's management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar's test of gain scores. Numeric comparison of first and last gain scores indicated women's scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.
Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysisAims/hypothesis: FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS.
Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasiaObjectives: High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined.
Novel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell PlasticityIntroduction: Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes.
Nonclassic congenital adrenal hyperplasia.Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.
Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome.Polycystic ovary syndrome (PCOS) is one of the most common endocrine/metabolic disorders found in women, affecting approximately 105 million women worldwide. It is characterized by ovulatory dysfunction, often presenting as oligomenorrhea or amenorrhea and either clinical or biochemical hyperandrogenism. Combined oral contraceptive (COC) therapy has long been a cornerstone of care for women with PCOS. COC therapy often provides clinical improvement in the areas of excessive hair growth, unpredictable menses, acne, and weight gain. One of the main issues in COC therapy is choosing the most appropriate progestin component to provide the greatest anti androgenic effects. Drospirenone, a relatively new progestin, has shown benefit in the PCOS population when used in conjunction with ethinyl estradiol. We now review the role of COCs in PCOS, focusing specifically on drospirenone. Controversy over metabolic effects of COCs in PCOS is also discussed.
Lemierre's syndrome complicating pregnancy.Lemierre's syndrome is an anaerobic suppurative thrombophlebitis involving the internal jugular vein secondary to oropharyngeal infection. There is only one previous case report in pregnancy which was complicated by premature delivery of an infant that suffered significant neurological damage. We present an atypical case diagnosed in the second trimester with a live birth at term. By reporting this case, we hope to increase the awareness of obstetricians to the possibility of Lemierre's syndrome when patients present with signs of unabating oropharyngeal infection and pulmonary symptoms.