Search Results

You are looking at 1 - 10 of 10 items for

  • Author: Vasantha Padmanabhan x
  • Refine by access: All content x
Clear All Modify Search
Lindsay Ellsworth Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Lindsay Ellsworth in
Google Scholar
PubMed
Close
,
Emma Harman Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Emma Harman in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
, and
Brigid Gregg Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Brigid Gregg in
Google Scholar
PubMed
Close

The window of lactation is a critical period during which nutritional and environmental exposures impact lifelong metabolic disease risk. Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults can have lasting effects. This review will cover current literature on factors influencing lactational programming such as milk composition, maternal health status and environmental endocrine disruptors. The underlying mechanisms that have the potential to contribute to lactational programming of glucose homeostasis will also be addressed, as well as potential interventions to reduce offspring metabolic disease risk.

Free access
Hugo H Ortega
Search for other papers by Hugo H Ortega in
Google Scholar
PubMed
Close
,
Natalia R Salvetti
Search for other papers by Natalia R Salvetti in
Google Scholar
PubMed
Close
, and
Vasantha Padmanabhan Department of Morphological Sciences, Department of Pediatrics and the Reproductive Sciences Program, Faculty of Veterinary Sciences, National University of Litoral, Esperanza 3800, Santa Fe, Argentina and Argentine National Research Council (CONICET)

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close

Steroid hormones play an important role in reproduction and the receptors through which they signal change in a developmental time, follicle stage, and cell-specific manner. Disruption in steroid receptor expression affects follicle formation and differentiation. In this study, using prenatal testosterone (T) and dihydrotestosterone (DHT)-treated female sheep as model systems, we tested the hypothesis that prenatal androgen excess disrupts the developmental ontogeny of ovarian steroid receptor protein expression. Pregnant Suffolk ewes were injected twice weekly with T propionate or DHT propionate (a non-aromatizable androgen) in cottonseed oil from days 30 to 90 of gestation. Changes in ovarian estrogen receptors (ER; ESR1, ESR2), androgen receptor (AR) and progesterone receptor (PGR) proteins were determined at fetal (days 90 and 140), postpubertal (10 months), and adult (21 months; only prenatal T-treated sheep studied) ages by immunohistochemistry. Prenatal T and DHT treatment induced selective increase in AR but not ER or PGR expression in the stroma and granulosa cells of fetal days 90 and 140 ovaries. An increase in ESR1 and decrease in ESR2 immunostaining coupled with increased AR expression were evident in granulosa cells of antral follicles of 10- and 21-month-old prenatal T but not DHT-treated females (analyzed only at 10 months). These findings provide evidence that an early increase in ovarian AR is the first step in the altered ovarian developmental trajectory of prenatal T-treated females, and manifestations of postnatal ovarian dysfunction are likely facilitated via altered equilibrium of antral follicular granulosa cell ER/AR protein expression.

Free access
Muraly Puttabyatappa Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Muraly Puttabyatappa in
Google Scholar
PubMed
Close
,
Rodolfo C Cardoso Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Rodolfo C Cardoso in
Google Scholar
PubMed
Close
,
Carol Herkimer Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Carol Herkimer in
Google Scholar
PubMed
Close
,
Almudena Veiga-Lopez Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Almudena Veiga-Lopez in
Google Scholar
PubMed
Close
, and
Vasantha Padmanabhan Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close

Gestational testosterone (TS) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E2) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. This study investigated (1) the organizational contribution of prenatal estrogen excess and (2) the impact of postnatal exposure to E2 in modulating the effects of prenatal androgen excess (TS and dihydrotestosterone (DHT)) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with TS, DHT, E2, or E2 plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), TS, and DHT female offspring received a constant-release E2 implant postnatally. Findings revealed that (1) prenatal E2-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and (2) prenatal E2D-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal TS excess. More importantly, continuous postnatal E2-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E2 on tonic luteinizing hormone (LH) release, failed to amplify the E2-positive feedback and periovulatory defects induced by prenatal TS-treatment. Our results indicate that disruptions in E2-positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal TS-treatment are programmed predominantly during the prenatal life with postnatal exposure to E2 excess not contributing further to these disruptions.

Free access
Kwanyee Leung
Search for other papers by Kwanyee Leung in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan
Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
,
E. M. Convey
Search for other papers by E. M. Convey in
Google Scholar
PubMed
Close
,
R. E. Short
Search for other papers by R. E. Short in
Google Scholar
PubMed
Close
, and
R. B. Staigmiller
Search for other papers by R. B. Staigmiller in
Google Scholar
PubMed
Close

Summary. Changes in the ability of Gn-RH to induce gonadotrophin release with time after synchronization of oestrus was determined in 4 groups of 6 cows each. Cows were given Gn-RH at 40-min intervals for 6 h beginning at − 24,0,18 or 36 h (time 0 = removal of progestagen implant). Changes in concentration (ng/ml) of serum LH after Gn-RH averaged 2·9, 6·2, 6·4 and 33·4, whereas serum FSH averaged 25·7, 35·8, 35·8 and 97·3. Thus the responsiveness of the pituitary to Gn-RH had increased by 36 h after implant removal. Other groups of cows subjected to the same synchronization scheme were slaughtered at 0 h, 24 h or at various times after onset of oestrous behaviour. Gn-RH binding to crude pituitary membrane preparations was assessed. There was no apparent change in the affinity constant of Gn-RH-binding sites with time after synchronization. The number of Gn-RH-binding sites remained unchanged until the period of oestrus when a significant decline with time was detected. We conclude that the increase in pituitary responsiveness to Gn-RH that occurs before the preovulatory gonadotrophin surge was not directly associated with changes in number or affinity of pituitary Gn-RH-binding sites in crude pituitary membrane preparations.

Free access
Charles L Bormann Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA

Search for other papers by Charles L Bormann in
Google Scholar
PubMed
Close
,
Gary D Smith Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA

Search for other papers by Gary D Smith in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
, and
Theresa M Lee Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA
Departments of, Obstetrics and Gynecology, Molecular and Integrative Physiology, Urology, Pediatrics, Reproductive Sciences Program, Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA

Search for other papers by Theresa M Lee in
Google Scholar
PubMed
Close

Androgens play important roles during the first trimester of intrauterine life, coinciding with genital tract differentiation, during virilization and maintenance of secondary male characteristics, and during initiation of spermatogenesis. Little is known about the impact of inappropriate exposure to excess androgens during fetal development on male sexual maturation and reproduction. The objectives of this study were to determine the effects of prenatal 5α-dihydrotestosterone (DHT) and testosterone treatment during ovine sexual differentiation on post-pubertal testicular formation and subsequent potential for fertility as assessed by epididymal sperm characteristics. Rams prenatally treated with testosterone exhibited increased testicular weight relative to age-matched controls and prenatal DHT-treated rams (P<0.05), as well as elevated total and free testosterone concentrations compared with DHT-treated rams (P=0.07 and P<0.05 respectively). The percentage of progressively motile sperm from the epididymis was significantly reduced in prenatal DHT-treated but not testosterone-treated rams compared with control rams (P<0.05). The testosterone-treated rams had a greater number of germ cell layers than DHT-treated rams, but comparable to the controls. Prenatal testosterone-treated rams had significantly larger seminiferous tubule diameter and lumen diameter compared with prenatal DHT-treated (P<0.05). Significantly, more prenatal DHT- and testosterone-treated rams (P<0.05) had occluded tubule lumen than control rams. Findings from this study demonstrate that exposure to excess testosterone/DHT during male fetal sexual differentiation have differential effects on post-pubertal testicular size, seminiferous tubule size and function, sperm motility, and testosterone concentrations.

Free access
Daniel A Dumesic Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Search for other papers by Daniel A Dumesic in
Google Scholar
PubMed
Close
,
Luis R Hoyos Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Search for other papers by Luis R Hoyos in
Google Scholar
PubMed
Close
,
Gregorio D Chazenbalk Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Search for other papers by Gregorio D Chazenbalk in
Google Scholar
PubMed
Close
,
Rajanigandha Naik Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Search for other papers by Rajanigandha Naik in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
, and
David H Abbott Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA

Search for other papers by David H Abbott in
Google Scholar
PubMed
Close

Developmental origins of adult disease (DoHAD) refers to critical gestational ages during human fetal development and beyond when the endocrine metabolic status of the mother can permanently program the physiology and/or morphology of the fetus, modifying its susceptibility to disease after birth. The aim of this review is to address how DoHAD plays an important role in the phenotypic expression of polycystic ovary syndrome (PCOS), the most common endocrinopathy of women characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. Clinical studies of PCOS women are integrated with findings from relevant animal models to show how intergenerational transmission of these central components of PCOS are programmed through an altered maternal endocrine–metabolic environment that adversely affects the female fetus and long-term offspring health. Prenatal testosterone treatment in monkeys and sheep have been particularly crucial in our understanding of developmental programming of PCOS because organ system differentiation in these species, as in humans, occurs during fetal life. These animal models, along with altricial rodents, produce permanent PCOS-like phenotypes variably characterized by LH hypersecretion from reduced steroid-negative feedback, hyperandrogenism, ovulatory dysfunction, increased adiposity, impaired glucose-insulin homeostasis and other metabolic abnormalities. The review concludes that DoHAD underlies the phenotypic expression of PCOS through an altered maternal endocrine–metabolic environment that can induce epigenetic modifications of fetal genetic susceptibility to PCOS after birth. It calls for improved maternal endocrine–metabolic health of PCOS women to lower their risks of pregnancy-related complications and to potentially reduce intergenerational susceptibility to PCOS and its metabolic derangements in offspring.

Free access
Mónica P Recabarren
Search for other papers by Mónica P Recabarren in
Google Scholar
PubMed
Close
,
Pedro P Rojas-Garcia
Search for other papers by Pedro P Rojas-Garcia in
Google Scholar
PubMed
Close
,
Ralf Einspanier Laboratory of Animal Physiology and Endocrinology, Institute of Veterinary Biochemistry, Departments of Pediatrics and Reproductive Sciences Program, Laboratory of Endocrinology and Metabolism, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán CP 3812120, Chile

Search for other papers by Ralf Einspanier in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Laboratory of Animal Physiology and Endocrinology, Institute of Veterinary Biochemistry, Departments of Pediatrics and Reproductive Sciences Program, Laboratory of Endocrinology and Metabolism, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán CP 3812120, Chile

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
,
Teresa Sir-Petermann Laboratory of Animal Physiology and Endocrinology, Institute of Veterinary Biochemistry, Departments of Pediatrics and Reproductive Sciences Program, Laboratory of Endocrinology and Metabolism, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán CP 3812120, Chile

Search for other papers by Teresa Sir-Petermann in
Google Scholar
PubMed
Close
, and
Sergio E Recabarren
Search for other papers by Sergio E Recabarren in
Google Scholar
PubMed
Close

Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus–pituitary–ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (n=6) and males born to ewes exposed to twice weekly injections of 30 mg testosterone propionate from days 30 to 90 and of 40 mg testosterone propionate from days 90 to 120 of gestation (n=6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH.

Free access
Christine Margaret Whitelaw
Search for other papers by Christine Margaret Whitelaw in
Google Scholar
PubMed
Close
,
Jane Elizabeth Robinson
Search for other papers by Jane Elizabeth Robinson in
Google Scholar
PubMed
Close
,
George Ballantine Chambers
Search for other papers by George Ballantine Chambers in
Google Scholar
PubMed
Close
,
Peter Hastie
Search for other papers by Peter Hastie in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Division of Cell Sciences, Department of Pediatrics and Psychiatry, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
,
Robert Charles Thompson Division of Cell Sciences, Department of Pediatrics and Psychiatry, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, UK

Search for other papers by Robert Charles Thompson in
Google Scholar
PubMed
Close
, and
Neil Price Evans
Search for other papers by Neil Price Evans in
Google Scholar
PubMed
Close

The neurotransmitters/neuromodulators galanin (GAL) and galanin-like peptide (GALP) are known to operate through three G protein-coupled receptors, GALR1, GALR2 and GALR3. The aim of this study was to investigate changes in expression of mRNA for galanin, GALP and GALR1–3 in the hypothalamus and pituitary gland, of male and female sheep, to determine how expression changed in association with growth and the attainment of reproductive competence. Tissue samples from the hypothalami and pituitary glands were analysed from late foetal and pre-pubertal lambs and adult sheep. Although mRNA for galanin and GALR1-3 was present in both tissues, at all ages and in both genders, quantification of GALP mRNA was not possible due to its low levels of expression. mRNA expression for both galanin and its receptors was seen to change significantly in both tissues as a function of age. Specifically, hypothalamic galanin mRNA expression increased with age in the male, but decreased with age in the female pituitary gland. mRNA expression for all receptors increased between foetal and pre-pubertal age groups and decreased significantly between pre-pubertal and adult animals. The results indicate that the expression of mRNA for galanin and its receptors changes dynamically with age and those significant differences exist with regard to tissue type and gender. These changes suggest that galaninergic neuroendocrine systems could be involved in the regulation of ovine growth and or the development of reproductive competence. The roles played by these systems in the sheep, however, may differ from other species, in particular the neuroendocrine link between nutrition and reproduction and GALR1's role in pituitary signalling.

Free access
Claudio Parra Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Claudio Parra in
Google Scholar
PubMed
Close
,
Jenny L Fiedler Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Jenny L Fiedler in
Google Scholar
PubMed
Close
,
S Leticia Luna Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by S Leticia Luna in
Google Scholar
PubMed
Close
,
Monika Greiner Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Monika Greiner in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
, and
Hernán E Lara Lab. Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, Facultad de Química y Farmacia, Universidad de Valparaíso and Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Hernán E Lara in
Google Scholar
PubMed
Close

Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats. Our findings show that androgen and estradiol release from ovaries obtained during different stages of rat estrous cycle mimic cyclic changes in steroid release observed in vivo with maximal release occurring during late proestrus. VIP increased androgen release from ovaries of all cycle stages except late proestrus and estradiol release from all cycle stages. Increases in VIP-induced androgen and estradiol release were maximal at early proestrus. Inclusion of saturating concentrations of androstenedione increased magnitude of VIP-induced estradiol release at diestrus and estrus but not proestrus. Magnitude of VIP-induced androgen and estradiol release tended to be greater in the ovaries from EV-treated rats with polycystic ovary compared with estrous controls. At the tissue level, ovarian VIP concentration was cycle stage dependent with highest level seen in diestrus. Maximum concentration of VIP was found in EV-treated rats. Changes in VIP were inversely related to changes in ovarian nerve growth factor, a neuropeptide involved in ovarian androgen secretion. These results strongly suggest that intraovarian VIP participates in the control of estradiol secretion during the rat estrous cycle and possibly in the maintenance of increased ovarian estradiol secretory activity of EV-treated rats.

Free access
Hadrian M Kinnear Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Hadrian M Kinnear in
Google Scholar
PubMed
Close
,
Claire E Tomaszewski Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Claire E Tomaszewski in
Google Scholar
PubMed
Close
,
Alexis L Chang Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Alexis L Chang in
Google Scholar
PubMed
Close
,
Molly B Moravek Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
Division of Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, Michigan, USA
Department of Urology, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Molly B Moravek in
Google Scholar
PubMed
Close
,
Min Xu Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
Division of Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Min Xu in
Google Scholar
PubMed
Close
,
Vasantha Padmanabhan Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Vasantha Padmanabhan in
Google Scholar
PubMed
Close
, and
Ariella Shikanov Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA

Search for other papers by Ariella Shikanov in
Google Scholar
PubMed
Close

Historically, research in ovarian biology has focused on folliculogenesis, but recently the ovarian stroma has become an exciting new frontier for research, holding critical keys to understanding complex ovarian dynamics. Ovarian follicles, which are the functional units of the ovary, comprise the ovarian parenchyma, while the ovarian stroma thus refers to the inverse or the components of the ovary that are not ovarian follicles. The ovarian stroma includes more general components such as immune cells, blood vessels, nerves, and lymphatic vessels, as well as ovary-specific components including ovarian surface epithelium, tunica albuginea, intraovarian rete ovarii, hilar cells, stem cells, and a majority of incompletely characterized stromal cells including the fibroblast-like, spindle-shaped, and interstitial cells. The stroma also includes ovarian extracellular matrix components. This review combines foundational and emerging scholarship regarding the structures and roles of the different components of the ovarian stroma in normal physiology. This is followed by a discussion of key areas for further research regarding the ovarian stroma, including elucidating theca cell origins, understanding stromal cell hormone production and responsiveness, investigating pathological conditions such as polycystic ovary syndrome (PCOS), developing artificial ovary technology, and using technological advances to further delineate the multiple stromal cell types.

Free access