Objective To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome, taking into account maternal characteristics and assisted reproductive technology.Design Population based cohort study.

The action of steroid hormones is primarily mediated via a process that involves hormone binding to specific receptors in target cells, which leads to transcriptional activation of steroid-responsive genes and, subsequently, to a modification of cellular responses. The aim of the present study was to obtain information about the dynamics of the two types of estrogen receptors (ERs), alpha and beta, by comparing their concentration and distribution in the reproductive tract of the rat during the estrous cycle. Twenty-four 55- to 60-day-old female Sprague-Dawley rats were used. The stage of estrous cycle was determined by vaginal smear. ERalpha was the dominating subtype in uterus, oviduct, and cervix/vagina, with the distribution varying in stroma and epithelium during the estrous cycle. A low level of ERalpha mRNA was observed in ovarian stromal cells, with some scattered positive cells found among granulosa cells. ERbeta expression was observed in the different compartments of uterus and cervix/vagina, but cyclic variation during the estrous cycle was less evident than that of ERalpha. Only a few scattered cells that contained ERbeta mRNA were observed in oviduct. ERbeta mRNA was highly expressed in granulosa cells of developing follicles, with a weaker hybridization signal in new corpora lutea. Immunohistochemistry showed that protein levels of ERalpha and ERbeta have distinct specificity for tissues and cell types, similar to their respective levels of mRNA, as assessed by in situ hybridization. The precise physiological function and importance of ERbeta is still unclear. The relative physiological and pathological function of each ER subtype in the female reproductive tract remains to be further evaluated.

Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.

The uterus is an important target organ for steroid hormones. The effects of these hormones are mediated via specific receptors. The aim of this study was to compare the expression, distribution, and regulation of estrogen receptor (ER) alpha and beta in the rat uterus in order to establish possible different biological roles for the two receptor forms. Ovariectomized rats were treated with either estradiol (E(2)), progesterone (P(4)), or combinations of these for 24 or 48 h. The mRNA levels were measured by solution hybridization. Distribution of the mRNAs and receptor proteins was detected by in situ hybridization and immunohistochemistry. The results showed that ERalpha is the dominating subtype in the rat uterus. E(2) seemed to increase the ERalpha mRNA level in the glandular and luminal epithelium, but it caused a decrease of the immunostaining intensity in the glandular epithelium. P(4) reduced ERalpha expression in luminal epithelium whereas no effect was seen in the glandular epithelium. E(2) or P(4) did not alter the expression of ERbeta, on either the mRNA or protein level. In conclusion, the distribution and regulation of ERalpha and ERbeta differ in the different compartments of the rat uterus. The complex uterine responses to E(2) and P(4) are directly or indirectly mediated by differential cell-specific expression of their receptors. The low expression in the uterus and the limited regulation by gonadal steroids in this study suggest that ERbeta probably plays a minor role in the regulation of uterine physiology.

The human uterine cervix is a fibrous organ with a high connective tissue content. An extensive remodeling of the connective tissue prior to parturition, i.e., cervical ripening, requires the presence of proteolytic enzymes. The exact mechanism of cervical ripening has not been clarified. We evaluated in vivo distribution and expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in the human cervix at term pregnancy and immediately after parturition compared with the nonpregnant state. Cervical biopsies were obtained from term pregnant, postpartum, and nonpregnant women. MMP-2 and MMP-9 proteins were localized by immunohistochemistry. Messenger RNA levels of MMP-2 and MMP-9 were evaluated by relative quantitative reverse transcription-polymerase chain reaction (RT-PCR) using an invariable internal standard. The mRNA levels of MMP-2 and MMP-9 were increased in the cervix at term pregnancy and postpartum compared with the nonpregnant state. Cervical stromal fibroblasts and smooth muscle cells were identified as main sources of MMP-2, whereas the MMP-9 protein was observed exclusively in invading leukocytes. These data indicate the involvement of MMP-2 and MMP-9 in the cervical ripening process.

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Nulliparity, advanced maternal age and obesity were the strongest risk factors for postterm pregnancy and CS following labor induction in postterm pregnancy. Including maternal risk factors to the cervical assessment may improve prediction of vaginal delivery following labor induction in postterm pregnancy.

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