Daniel Dumesic - Academia.edu (original) (raw)

Papers by Daniel Dumesic

Biology of Reproduction, 2008

Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits... more Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH.

Endocrine reviews, 2015

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse re... more Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities...

Journal of Women's Health & Gender-Based Medicine, 2000

Croatian medical journal, Jan 20, 2015

To identify characteristic risk factors of preterm birth in Central and Eastern Europe and explor... more To identify characteristic risk factors of preterm birth in Central and Eastern Europe and explore the differences from other developed countries. Data on 33 794 term and 3867 preterm births (<37 wks.) were extracted in a retrospective study between January 1, 2007 and December 31, 2009. The study took place in 6 centers in 5 countries: Czech Republic, Hungary (two centers), Romania, Slovakia, and Ukraine. Data on historical risk factors, pregnancy complications, and special testing were gathered. Preterm birth frequencies and relevant risk factors were analyzed using Statistical Analysis System (SAS) software. All the factors selected for study (history of smoking, diabetes, chronic hypertension, current diabetes, preeclampsia, progesterone use, current smoking, body mass index, iron use and anemia during pregnancy), except the history of diabetes were predictive of preterm birth across all participating European centers. Preterm birth was at least 2.4 times more likely with smo...

Gynäkologisch-geburtshilfliche Rundschau, 1987

Reproductive toxicology (Elmsford, N.Y.)

To determine whether pioglitazone will improve menstrual cyclicity in a fetal programming model f... more To determine whether pioglitazone will improve menstrual cyclicity in a fetal programming model for polycystic ovary syndrome. Eight prenatally androgenized (PA) and 5 control female rhesus monkeys of similar age, body weight and body mass index received an oral placebo daily for 6-7 months followed, after at least 90 days, by daily oral dosing with pioglitazone (3mg/kg) for an additional 6-7 months. Blood was sampled thrice weekly to monitor ovulatory function, and a variety of endocrine challenges were performed to quantify changes in ovarian, gonadotropin and glucoregulatory function. Pioglitazone normalized menstrual cycles in 5 out of 8 (62%) PA females (pioglitazone responsive; Pio(RESP)). Pioglitazone increased serum 17alpha-hydroxyprogesterone responses to an hCG injection in Pio(RESP) PA females, while diminishing serum progesterone, and increasing DHEA and estradiol responses to hCG in Pio(RESP) PA and all normal females. Insulin resistance plays a mechanistic role in main...

Clinical and Translational Medicine, 2014

In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were introduced to the scienti... more In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were introduced to the scientific community, offering potential resolution to the issue of teratoma formation that plagues both embryonic stem (ES) and induced pluripotent (iPS) stem cells. Isolated from human bone marrow, dermal fibroblasts, adipose tissue and commercially available adipose stem cells (ASCs) under severe cellular stress conditions, Muse cells self-renew in a controlled manner and do not form teratomas when injected into immune-deficient mice. Furthermore, Muse cells express classic pluripotency markers and differentiate into cells from the three embryonic germ layers both spontaneously and under media-specific induction. When transplanted in vivo, Muse cells contribute to tissue generation and repair. This review delves into the aspects of Muse cells that set them apart from ES, iPS, and various reported adult pluripotent stem cell lines, with specific emphasis on Muse cells derived from adipose tissue (Muse-AT), and their potential to revolutionize the field of regenerative medicine and stem cell therapy.

PLoS ONE, 2014

Polycystic ovary syndrome (PCOS) is prevalent in reproductive-aged women and confounded by metabo... more Polycystic ovary syndrome (PCOS) is prevalent in reproductive-aged women and confounded by metabolic morbidities, including insulin resistance and type 2 diabetes. Although the etiology of PCOS is undefined, contribution of prenatal androgen (PA) exposure has been proposed in a rhesus monkey model as premenopausal PA female adults have PCOS-like phenotypes in addition to insulin resistance and decreased glucose tolerance. PA female infants exhibit relative hyperinsulinemia, suggesting prenatal sequelae of androgen excess on glucose metabolism and an antecedent to future metabolic disease. We assessed consequences of PA exposure on pancreatic islet morphology to identify evidence of programming on islet development. Islet counts and size were quantified and correlated with data from intravenous glucose tolerance tests (ivGTT) obtained from dams and their offspring. Average islet size was decreased in PA female infants along with corresponding increases in islet number, while islet fractional area was preserved. Infants also demonstrated an increase in both the proliferation marker Ki67 within islets and the beta to alpha cell ratio suggestive of enhanced beta cell expansion. PA adult females have reduced proportion of small islets without changes in proliferative or apoptotic markers, or in beta to alpha cell ratios. Together, these data suggest in utero androgen excess combined with mild maternal glucose intolerance alter infant and adult islet morphology, implicating deviant islet development. Marked infant, but subtle adult, morphological differences provide evidence of islet post-natal plasticity in adapting to changing physiologic demands: from insulin sensitivity and relative hypersecretion to insulin resistance and diminished insulin response to glucose in the mature PCOS-like phenotype.

To determine whether prenatal T propionate exposure be- ginning gestational d 40 - 44 (early-trea... more To determine whether prenatal T propionate exposure be- ginning gestational d 40 - 44 (early-treated) or 100 -115 (late- treated) affects oocyte competence, five early-treated and five late-treated prenatally androgenized and five normal monkeys underwent recombinant human FSH injections with oocyte-retrieval after hCG administration. Serum FSH, LH, estradiol (E2), progesterone (P4), androstenedione (A4), T, and dihydrotestosterone were measured basally, during

Introduction-Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in ... more Introduction-Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with PCOS women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI).

PLoS ONE, 2011

Introduction: Previous studies highlight a complex relationship between lineage and phenotype for... more Introduction: 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.

Context: Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is c... more Context: Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by increased ovar- ian androgen production and arrested follicle development and is frequently associated with insulin resistance. These PCOS phe- notypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. Objective: The objective of this study was to examine whether the perturbations in

Ultrasound in Obstetrics and Gynecology, 2004

To characterize ovarian morphology in a group of ovulatory, non-hirsute women with infertility an... more To characterize ovarian morphology in a group of ovulatory, non-hirsute women with infertility and normal circulating levels of gonadotropins and sex steroids. Thirty-three women with normal physical examinations, regular ovulatory menses, and absence of hirsutism (Ferriman-Gallwey score < or = 7) were studied. No woman had thyroid disease, galactorrhea, polycystic ovary syndrome, 21-hydroxylase deficiency or diabetes. Two-dimensional (2D) transvaginal sonography (TVS) was used to measure follicle size and ovarian volume on menstrual cycle day 5. Three-dimensional (3D) TVS images were stored to determine the number of follicles (measuring 2-10 mm in diameter) in the largest sonographic plane. Fasting blood sampling and oral glucose tolerance testing were performed to assess serum gonadotropin and sex steroid levels as well as glucose tolerance. The median ovarian volume by 2D-TVS imaging was 7.2 (range, 2.3-15.8) cm(3) (n = 64 ovaries). No follicles were > 10 mm in diameter. The median number of follicles by 3D-TVS was 4 (range, 2-8) (n = 63 ovaries) in the largest sonographic plane. Fourteen of 63 ovaries (22%) had six or more small follicles in one plane distributed within normal stroma (multifollicular ovary, MFO). No ovary had 10 or more follicles in one plane located within abundant stroma (polycystic ovary). Of 33 women examined, 20 women (61%) had apparently normal ovaries bilaterally, while 13 (39%) had at least one MFO. There were no significant differences between women with and those without MFO in serum gonadotropin and steroid levels or glucose tolerance. MFO is a common morphological variant in non-hirsute ovulatory women with normal gonadotropin secretion and ovarian steroidogenesis.

Fertility and Sterility, 2007

remained below 2% through 2004, then increased to 3% in 2005 and 7% in 2006. The proportion of al... more remained below 2% through 2004, then increased to 3% in 2005 and 7% in 2006. The proportion of all DO ETs that were eSET rose each year from 2% in 2002 to 18% in 2006. Pregnancy rates for auto eSET were 61% (68% in 2006) compared to 60% (61% in 2006) for transfers of 2 blastocysts. Pregnancy rates for DO eSET were 64% (67% in 2006) compared to 71% (67% in 2006) for transfers of 2 blastocysts. Only 1.4% of all eSET pregnancies were twins, compared to twinning rates of 51% for auto and 60% for DO pregnancies following elective transfer of 2 blastocysts.

Seminars in Reproductive Medicine, 2014

The maternal-fetal environment plays an important role in developmental programming of adult dise... more The maternal-fetal environment plays an important role in developmental programming of adult disease. Metabolic and hormonal dysfunction during human fetal development accompanies gestational diabetes as a common occurrence in mothers with polycystic ovary syndrome (PCOS), while human fetal androgen excess from congenital adrenal hyperplasia or virilizing tumors precedes PCOS-like symptoms after birth. To date, clinical studies of infant blood levels at term have yet to confirm that human fetal androgen excess promotes PCOS development after birth. Earlier in development, however, circulating androgen levels in the second trimester female human fetus can normally rise into the male range. Furthermore, midgestational amniotic testosterone levels are elevated in female fetuses of PCOS compared with normal mothers and might influence fetal development because experimentally induced fetal androgen excess in animals produces a PCOS-like phenotype with reproductive and metabolic dysfunction. Such alterations in the maternal-fetal environment likely program adult PCOS by epigenetic modifications of genetic susceptibility of the fetus to PCOS after birth. Understanding this phenomenon requires advanced fetal surveillance technologies and postnatal assessment of midgestational androgen exposure for new clinical strategies to improve reproduction in PCOS women, optimize long-term health of their offspring, and minimize susceptibility to acquiring PCOS in future generations.

Reproductive BioMedicine Online, 2004

A prospective randomized trial was performed to compare post-thaw development of murine blastocys... more A prospective randomized trial was performed to compare post-thaw development of murine blastocysts following programmable rate freezing and two methods of vitrification. Frozen 2-cell murine embryos (n = 429) thawed and cultured for 48 h, were randomly allocated by stage of development into four groups: control (not refrozen), programmable rate freezing (PR) in 0.25 ml straws, vitrification in flexible micropipettes by immersion in super-cooled (VSC) liquid nitrogen (LN2), and vitrification in flexible micropipettes by immersion in LN2 (VLN). Survival, developmental stage progression, presence or absence of an inner cell mass (ICM), and cell counts were recorded 24 h post-thaw. All measured outcomes were different between embryos from the control group and all freezing methods. Controlled-rate freezing resulted in the lowest total cell counts and fewest embryos with a distinct ICM. A higher percentage of embryos survived 24 h post-thaw, progressed to more advanced developmental stages and had higher total cell counts after VLN compared with PR. Moreover, fewer embryos, frozen by either PR or VSC, contained a detectable ICM compared with VLN. These data demonstrate that vitrification may be a better method for freezing murine blastocysts than PR, and may prove to be a superior method for freezing human blastocysts.

Obstetrical & Gynecological Survey, 1987

Since the discovery and synthesis of gonadotropin-releasing hormone (GnRH) in 1971, numerous long... more Since the discovery and synthesis of gonadotropin-releasing hormone (GnRH) in 1971, numerous long-acting agonistic and antagonistic analogs have been synthesized. Agonistic analogs were found to desensitize pituitary GnRH receptors with chronic use, resulting in decreased gonadotropin secretion and a hypogonadal state. These analogs are being investigated as potential contraceptives and in the treatment of several conditions in which decreased gonadal steroid production is desired. Substantial progress has been made in these areas. The purpose of this review is to provide the clinician with data regarding the potential clinical utility of this class of peptides.

Obstetrical & Gynecological Survey, 2008

Folliculogenesis is a complex process, in which multiple endocrine and intraovarian paracrine int... more Folliculogenesis is a complex process, in which multiple endocrine and intraovarian paracrine interactions create a changing intrafollicular microenvironment for appropriate oocyte development. Within this microenvironment, bidirectional cumulus cell-oocyte signaling governs the gradual acquisition of developmental competence by the oocyte, defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. These regulatory mechanisms of follicle growth, controlled in part by the oocyte itself, are susceptible to derangement in polycystic ovary syndrome (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism, insulin resistance, and paracrine dysregulation of follicle development. Consequently, only a subset of PCOS patients experience reduced pregnancy outcome after ovarian stimulation for in vitro fertilization. Recent data implicate functional associations between endocrine/paracrine abnormalities, metabolic dysfunction, and altered oocyte gene expression with impaired oocyte developmental competence in women with PCOS. Therefore, an understanding of how developmentally relevant endocrine/paracrine factors interact to promote optimal oocyte developmental is crucial to identify those PCOS patients who might benefit from long-term correction of follicle growth to improve fertility, optimize follicular responsiveness to gonadotropin therapy, and enhance pregnancy outcome by in vitro fertilization.