C19 steroids are converted to estrogens in a number of tissues by specific form cytochrome P450, namely aromatase P450 (P450arom). Adipose tissue is the principal site estrogen formation postmenopausal women. Aromatase activity as well P450arom transcripts primarily reside stromal cell component adipose tissue. Studies designed investigate whether increased local breast influences growth cancers have yielded discrepant results. In an attempt clarify this controversy, was obtained from four...

The structural gene encoding aromatase cytochrome P-450 (P-450AROM) was isolated from human genomic DNA. spans at least 52 kilobases and is composed of 10 exons, the first which untranslated. Analysis transcription initiation site P-450AROM mRNA reveals differential use 1 3 consecutive G residues cap site. DNA sequence analysis indicates that has a putative TATA (ATAAAA) −23 base pairs (bp) CAAT binding sequences beginning −41, −67, −83 bp. 5′-flanking region contains similar to consensus...

Estrogen biosynthesis is catalyzed by a microsomal enzyme, aromatase cytochrome P450 (P45Oarom; the product of CYPl9 gene).The human CYP19 gene comprises nine coding exons, 11-X.Additionally, tissuespecific expression determined use promoters, which give rise to P45Oarom transcripts with unique 5'-noncoding sequences.In placenta, P4SOarom contain one two 5'untranslated 1.1 or 1.2, while ovarian instead sequence consistent promoter, PII, proximal start translation.To characterize present in...

The formation of estrogens from C19 steroids is catalyzed by a specific form cytochrome P450, aromatase P450 (P450AROM; the product CYP19 gene). Previous studies have demonstrated that activity in human adipose and ovarian granulosa cells subject to complex multifactorial regulation changes are correlated with levels mRNA encoding P450AROM. We previously isolated gene. Two unique untranslated first exons (exons I.1 I.2) been identified for P450AROM placenta. Although proportion transcripts...

Successful delivery of the fetus (parturition) depends on coordinate interactions between uterus and cervix. A majority (70%) mice deficient in type 1 isozyme steroid 5α-reductase fail to deliver their young at term thus manifest a parturition defect. Using vitro vivo measurements we show here that rhythmic contractions occur normally these mutant end gestation. In contrast, cervix animal fails ripen as judged by biomechanical, histological, endocrinological assays. Impaired metabolism...

Cervical remodeling during pregnancy and parturition is a single progressive process that can be loosely divided into four overlapping phases termed softening, ripening, dilation/labor, post partum repair. Elucidating the molecular mechanisms facilitate all of cervical critical for an understanding identifying processes are misregulated in preterm labor, significant cause perinatal morbidity. In present study, biomechanical measurements indicate softening was initiated between gestation days...

Two steroid 5 alpha-reductase isozymes designated type 1 and 2 synthesize alpha-reduced androgens other hormones. Naturally occurring mutations in the gene encoding cause male pseudohermaphroditism, indicating that this isozyme is responsible for synthesis of dihydrotestosterone required virilization embryonic urogenital tract. To determine physiological role 1, homologous recombination mouse stem cells was used to produce female mice with a disruption (null allele) (Srd5a1). Male lacking...

The biosynthesis of estrogens from androgens is catalyzed by a enzyme the endoplasmic reticulum termed aromatase cytochrome P-450 (P-450AROM). gene encoding P-450AROM was isolated in our laboratory utilizing full-length cDNA and primer-extended obtained human placental libraries as probes. We have found that spans at least 75 kilobases region protein comprised nine exons. In addition, there are two untranslated exons, I.1 I.2, upstream which putative promoter sequences thought to be...

We report the development of an all-fiber-optic scanning endomicroscope capable high-resolution second harmonic generation (SHG) imaging biological tissues and demonstrate its utility for monitoring remodeling cervical collagen during gestation in mice. The has overall 2.0 mm diameter consists a single customized double-clad fiber, compact rapid two-dimensional beam scanner, miniature compound objective lens excitation delivery, scanning, focusing, efficient SHG signal collection....

A greater understanding of the parturition process is essential in prevention preterm birth, which occurs 12.7% infants born United States annually. Cervical remodeling a critical component this process. Beginning early pregnancy, requires cumulative, progressive changes cervical extracellular matrix (ECM) that result reorganization collagen fibril structure with gradual loss tensile strength. In current study, we undertook detailed biochemical analysis factors cervix modulate during mouse...

The changes in the mechanical integrity of cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively mice with progressing gestation leading soft at term. During this process, mature crosslinked hypothesized be replaced immature less facilitate cervical softening and ripening. To determine role collagen crosslinks normal mouse remodeling, tensile load-to-break tests were conducted following time points: nonpregnant (NP), day (d)...

Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average homozygous females is 2.7 pups vs. 8.0 wild controls. Oogenesis, fertilization, implantation, and placental morphology appear normal the mutant animals. Fetal loss occurs between gestation days 10.75 11.0 commensurate with midpregnancy surge androgen production an induction of expression decidua mice. Plasma levels androstenedione testosterone are 2- to 3-fold higher on day 9, estradiol...

Abstract Preterm birth occurs at a rate of 12.7% in the U.S. and is primary cause fetal morbidity first year life as well later health problems. Elucidation mechanisms controlling cervical remodeling critical for development therapies to reduce incidence prematurity. The extracellular matrix must be disorganized during labor allow birth, followed by rapid repair postpartum. Leukocytes infiltrate cervix before after are proposed regulate ripening via release proteolytic enzymes. In current...

We use second harmonic generation (SHG) microscopy to assess changes in collagen structure of murine cervix during cervical remodeling normal pregnancy and a preterm birth model. Visual inspection SHG images revealed substantial morphology throughout gestation. collected both the forward backward directions were analyzed quantitatively for overall mean intensity, intensity ratio, fiber size, porosity. Changes ratio take place early pregnancy, suggesting that submicroscopic fibril size...

In the current study, mechanisms of premature cervical ripening in murine models preterm birth resulting from infection or early progesterone withdrawal were compared with process term ripening. Tissue morphology, weight, gene expression, and collagen content along immune cell populations evaluated. Premature induced by receptor antagonist mifepristone results an acceleration processes place during as well partial activation proinflammatory immunosuppressive observed postpartum repair....

Glycosaminoglycans (GAG) have diverse functions that regulate macromolecular assembly in the extracellular matrix. During pregnancy, rigid cervix transforms to a pliable structure allow birth. Quantitative assessment of cervical GAG is prerequisite identify term and preterm In current study, total levels increased at term, yet abundance, chain length, sulfation sulfated remained constant. The increase resulted exclusively from an hyaluronan (HA). HA can form large structures promote...

Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has long been proposed play an essential role in disorganization the collagen-rich extracellular matrix allow for maximal compliance and dilation cervix during birth process. Here, we show that HA is not increased distensibility pregnancy. Rather, cervicovaginal plays unanticipated important epithelial barrier protection lower reproductive tract. Specifically, depletion vagina resulted inappropriate differentiation...

The extracellular matrix (ECM) plays an active and dynamic role that both reflects facilitates the functional requirements of a tissue. mature ECM nonpregnant cervix is drastically reorganized during pregnancy to drive changes in tissue mechanics ensure safe birth. In this study, our research on mice deficient proteoglycan decorin have led finding progesterone estrogen play distinct complementary roles orchestrate structural reorganization collagen elastic fibers pregnancy. Abnormalities...