In utero exposure to cigarette smoke dysregulates human fetal ovarian developmental signalling

STUDY QUESTION How does maternal cigarette smoking disturb development of the human fetal ovary?<p></p> SUMMARY ANSWER Maternal smoking increases fetal estrogen titres and dysregulates several developmental processes in the fetal ovary.<p></p> WHAT IS KNOWN ALREADY Exposure to maternal cigarette smoking during gestation reduces human fetal ovarian cell numbers, germ cell proliferation and subsequent adult fecundity.<p></p> STUDY DESIGN, SIZE, DURATION The effects of maternal cigarette smoking on the second trimester human fetal ovary, fetal endocrine signalling and fetal chemical burden were studied. A total of 105 fetuses were studied, 56 from mothers who smoked during pregnancy and 49 from those who did not.<p></p> PARTICIPANTS/MATERIALS, SETTING METHODS Ovary, liver and plasma samples were collected from electively terminated, normally progressing, second trimester human fetuses. Circulating fetal hormones, levels of 73 fetal ovarian transcripts, protein localization, density of oocytes/primordial follicles and levels of 16 polycyclic aromatic hydrocarbons (PAHs) in the fetal liver were determined.<p></p> MAIN RESULTS AND THE ROLE OF CHANCE Circulating fetal estrogen levels were very high and were increased by maternal smoking (ANOVA, P = 0.055–0.004 versus control). Smoke exposure also dysregulated (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.046–0.023) four fetal ovarian genes (cytochrome P450 scc [CYP11A1], NOBOX oogenesis homeobox [NOBOX], activator of apoptosis harakiri [HRK], nuclear receptor subfamily 2, group E, member 1 [NR2E1]), shifted the ovarian Inhibin βA/inhibin α ratio (NHBA/INHA) transcript ratio in favour of activin (ANOVA, P = 0.049 versus control) and reduced the proportion of dominant-negative estrogen receptor 2 (ERβ: ESR2) isoforms in half the exposed fetuses. PAHs, ligands for the aryl hydrocarbon receptor (AHR), were increased nearly 6-fold by maternal smoking (ANOVA, P = 0.011 versus control). A fifth transcript, COUP transcription factor 1 (nuclear receptor subfamily 2, group F, member 1: NR2F1, which contains multiple AHR-binding sites), was both significantly increased (ANOVA, P = 0.026 versus control) and dysregulated by (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.021) maternal smoking. NR2F1 is associated with repression of FSHR expression and smoke-exposed ovaries failed to show the normal increase in FSHR expression during the second trimester. There was a significantly higher number of DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 (DDX4) VASA-positive (ANOVA, P = 0.016 versus control), but not POU domain, class 1, transcription factor 1 (POU5F1) OCT3/4-positive, oocytes in smoke-exposed fetuses and this matched with a significantly higher number of primordial follicles (ANOVA, P = 0.024 versus control).<p></p> LIMITATIONS, REASONS FOR CAUTION The effects of maternal smoking on establishment of the maximum fetal primordial follicle pool cannot be reliably studied in our population since the process is not completed until 28 weeks of gestation and normal fetuses older than 21 weeks of gestation are not available for study. Our data suggest that some fetal ovaries are affected by smoke exposure while others are not, indicating that additional studies, with larger numbers, may show more significant effects.<p></p> WIDER IMPLICATIONS OF THE FINDINGS Fetal exposure to chemicals in cigarette smoke is known to lead to reduced fecundity in women. Our study suggests, for the first time, that this occurs via mechanisms involving activation of AHR, disruption of inhibin/activin and estrogen signalling, increased exposure to estrogen and dysregulation of multiple molecular pathways in the exposed human fetal ovary. Our data also suggest that alterations in the ESR2 positive and dominant negative isoforms may be associated with reduced sensitivity of some fetuses to increased estrogens and maternal smoking

Control of pests and weeds by natural enemies: an introduction to biological control

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Field Surveys for Natural Enemies of Banana Weevil, Cosmopolites Sordidus (Germar), in Indonesia with Emphasis on Searches for Egg and Larval Parasitoids

The banana weevil, an important pest on highland banana and plantain in Africa, is endemic to southeast Asia where it usually occurs in low numbers. This suggested the possibility of effective co-evolved natural enemies in its original range that might be used in a classical biological of banana weevil. Previous searches for natural enemies in southeast Asia, undertaken in the first half of the 20th century, encountered only generalist predators. Therefore, a search was undertaken for natural enemies of banana weevil on the islands of Sumatra and Java in Indonesia with emphasis on looking for egg or larval parasitoids. Two surveys were conducted September-November 2000 and March-November 2001in which approximately 640 and 25,000 eggs were collected and reared in the first and second survey respectively. Evidence of egg parasitism was initially suggested by the presence of Hymenopterous wings and body parts in rearing containers, but further rearing of more than 25,000 eggs failed to uncover further evidence of parasitism. This suggests that egg parasitism in Indonesia is rare. To assess larval parasitism, the larvae were reared on pieces of banana corm. Several dipterans were found in larval rearing containers, but taxonomic identifications of phorids and other dipterans obtained suggested that none of these were parasitoids Phorids were probably scavengers whose eggs were present in banana corms when they were brought to the laboratory. During the second survey (March-Nov 2001) we developed improved methods for efficiently collecting and rearing of banana weevil eggs and larvae. These techniques will facilitate future parasitoids surveys and will be useful to behavioral and ecological studies of the banana weevil. A complex of predatory ants, including species ofMyrmicinae, Ponerinae, Formicinae and Dolichoderinae, were found associated with banana plants and residues in the field. Adults and larvae of the ant Myopopone castanea (authorname) (Hymenoptera:Formicidae:Ponerinae) were observed attacking banana weevil larvae in crop residues. Predators in the orders Dermaptera and Coleoptera were also encountered. Ofthese, the histerid Plaesiusjavanus Erichsen appeared to be most important. While most of the predators encountered were nonspecific and unlikely to be important in banana weevil control, there is need for further work on egg and larval parasitoids in other areas such as southern India, which is the center of origin for plantain. Plantains are comprised of clones with greater susceptibility to banana weevil