Cord blood insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism.

BACKGROUND: Cryptorchidism, the most frequent congenital malformation in full-term male newborns, increases the risk of hypofertility and testicular cancer. Most cases remain idiopathic but epidemiological and experimental studies have suggested a role of both genetic and environmental factors. Physiological testicular descent is regulated by two major Leydig hormones: insulin-like peptide 3 (INSL3) and testosterone. OBJECTIVES: To study the endocrine context at birth as a reflection of late pregnancy in isolated idiopathic cryptorchidism and to analyse the possible disruptions of INSL3 and/or testosterone. METHODS: From a prospective case-control study at Nice University Hospital, we assessed 180 boys born after 34 weeks gestation: 52 cryptorchid (48 unilateral, 4 bilateral; 26 transient, 26 persistent), and 128 controls matched for term, weight and time of birth. INSL3 and testosterone were measured in cord blood and compared in both groups as were other components of the pituitary-gonadic axis: LH, HCG, FSH, AMH and SHBG. RESULTS: INSL3 was decreased in cryptorchid boys (P = 0·031), especially transient cryptorchid (P = 0·029), while testosterone was unchanged as were the other hormones measured. INSL3 was significantly decreased (P = 0·018) in the group of 20 with nonpalpable testes compared with the group of 21 with palpable testes (15 suprascrotal, five inguinal, one high scrotal) according to Scorer classification. In the whole population, INSL3 correlated positively with LH and negatively with AMH, but with no other measured hormones. CONCLUSIONS: INSL3 but not testosterone is decreased at birth in idiopathic cryptorchidism, especially in transient forms. This hormonal decrease may contribute to the impaired testicular descent along with genetic and anatomical factors. Whether foetal environment (nutritional and/or toxicological) interferes with INSL3 secretion in humans remains to be confirmed.

A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development.

STUDY QUESTION: Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)? SUMMARY ANSWER: In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production. WHAT IS KNOWN ALREADY: INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism. STUDY DESIGN, SIZE, DURATION: Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R² = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone. LIMITATIONS, REASONS FOR CAUTION: The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.

A root-knot nematode-secreted protein is injected into giant cells and targeted to the nuclei.

Root-knot nematodes (RKNs) are obligate endoparasites that maintain a biotrophic relationship with their hosts over a period of several weeks and induce the differentiation of root cells into specialized feeding cells. Nematode effectors synthesized in the oesophageal glands and injected into the plant tissue through the syringe-like stylet certainly play a central role in these processes. In a search for nematode effectors, we used comparative genomics on expressed sequence tag (EST) datasets to identify Meloidogyne incognita genes encoding proteins potentially secreted upon the early steps of infection. We identified three genes specifically expressed in the oesophageal glands of parasitic juveniles that encode predicted secreted proteins. One of these genes, Mi-EFF1 is a pioneer gene that has no similarity in databases and a predicted nuclear localization signal. We demonstrate that RKNs secrete Mi-EFF1 within the feeding site and show Mi-EFF1 targeting to the nuclei of the feeding cells. RKNs were previously shown to secrete proteins in the apoplasm of infected tissues. Our results show that nematodes sedentarily established at the feeding site also deliver proteins within plant cells through their stylet. The protein Mi-EFF1 injected within the feeding cells is targeted at the nuclei where it may manipulate nuclear functions of the host cell.

Sustained bloodstream release of persistent organic pollutants induced by extensive weight loss after bariatric surgery: Implications for women of childbearing age.

BACKGROUND: Lipophilic persistent organic pollutants (POPs) are stored in adipose tissues and released in case of weight loss. OBJECTIVES: To analyze the kinetics and characteristics of this release during drastic weight loss after bariatric surgery and compare the results in case of women of childbearing age (WCBA) with critical blood concentration thresholds. METHODS: 100 morbidly obese patients (73 women including 53 of childbearing age and 27 men) were screened before and 3, 6 and 12 months after bariatric surgery for serum concentrations of 67 congeners or metabolites of banned or not yet banned organohalogenated persistent pollutants, including highly lipophilic polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), brominated flame retardants (BFRs), and less lipophilic perfluorinated alkylated substances (PFASs). RESULTS: Circulating levels of all chemicals, except PFASs, increased progressively after surgery, reaching after one year an increase between 30 and 139% compared to initial pre-surgical levels; median levels increased for PCB153 from 36.8 to 86.4 ng/g lw (+130%), for dichlorodiphenyldichloroethylene (p,p'-DDE) from 59.8 to 136.1 ng/g lw (+120%), and for hexachlorobenzene (HCB) from 9.8 to 20.3 ng/g lw (+110%). Weight loss averaging 30% of initial body weight at 12 months in both sexes (mean: 40.0 kg for men, 36.1 kg for women), was the main parameter related to the concentration increases (3.1 to 3.6% per kilogram weight loss). They were not dependent on initial BMI, presence of metabolic syndrome or type of surgical procedure but influenced by gender and biochemical properties such as degree of chlorination for PCBs and/or lipophilicity since PFASs did not increase at all. ∑PCB6 in blood after one year exceeded the critical concentration threshold for 24.5% women of childbearing age (13/53) versus 3.6% (2/53) before surgery. DISCUSSION: Massive weight loss within the first year following bariatric surgery is associated with a sustained increase of circulating lipophilic POPs. Short- and long-term consequences should be considered, mostly for childbearing age obese women, because of potential health risks for the future fetus and breastfeeding infant.

Endocrine Disrupting Chemicals Interfere With Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism.

Cryptorchidism, a frequent genital malformation in male newborn, remains in most cases idiopathic. On the basis of experimental, epidemiological, and clinical data, it has been included in the testicular dysgenesis syndrome and believed to be influenced, together with genetic and anatomic factors, by maternal exposure to endocrine disrupting chemicals (EDCs). Here, we analyze how EDCs may interfere with the control of testicular descent, which is regulated by two Leydig cell hormones, testosterone, and insulin like peptide 3 (INSL3).

Breeding success of a marine central place forager in the context of climate change: A modeling approach.

In response to climate warming, a southward shift in productive frontal systems serving as the main foraging sites for many top predator species is likely to occur in Subantarctic areas. Central place foragers, such as seabirds and pinnipeds, are thus likely to cope with an increase in the distance between foraging locations and their land-based breeding colonies. Understanding how central place foragers should modify their foraging behavior in response to changes in prey accessibility appears crucial. A spatially explicit individual-based simulation model (Marine Central Place Forager Simulator (MarCPFS)), including bio-energetic components, was built to evaluate effects of possible changes in prey resources accessibility on individual performances and breeding success. The study was calibrated on a particular example: the Antarctic fur seal (Arctocephalus gazella), which alternates between oceanic areas in which females feed and the land-based colony in which they suckle their young over a 120 days rearing period. Our model shows the importance of the distance covered to feed and prey aggregation which appeared to be key factors to which animals are highly sensitive. Memorization and learning abilities also appear to be essential breeding success traits. Females were found to be most successful for intermediate levels of prey aggregation and short distance to the resource, resulting in optimal female body length. Increased distance to resources due to climate warming should hinder pups' growth and survival while female body length should increase.

Optimal resource allocation to survival and reproduction in parasitic wasps foraging in fragmented habitats.

Expansion and intensification of human land use represents the major cause of habitat fragmentation. Such fragmentation can have dramatic consequences on species richness and trophic interactions within food webs. Although the associated ecological consequences have been studied by several authors, the evolutionary effects on interacting species have received little research attention. Using a genetic algorithm, we quantified how habitat fragmentation and environmental variability affect the optimal reproductive strategies of parasitic wasps foraging for hosts. As observed in real animal species, the model is based on the existence of a negative trade-off between survival and reproduction resulting from competitive allocation of resources to either somatic maintenance or egg production. We also asked to what degree plasticity along this trade-off would be optimal, when plasticity is costly. We found that habitat fragmentation can indeed have strong effects on the reproductive strategies adopted by parasitoids. With increasing habitat fragmentation animals should invest in greater longevity with lower fecundity; yet, especially in unpredictable environments, some level of phenotypic plasticity should be selected for. Other consequences in terms of learning ability of foraging animals were also observed. The evolutionary consequences of these results are discussed.