Mitochondrial content and hepcidin are increased in obese pregnant mothers.

OBJECTIVE: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here, we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese maternal circulation. METHODS: Forty-one pregnant women were enrolled at elective cesarean section: 16 were normal weight (NW) and 25 were obese (OB). Obese women were further classified according to the presence/absence of maternal gestational diabetes mellitus (GDM); [OB/GDM(-)]: n = 15, [OB/GDM(+)]: n = 10. mtDNA and hepcidin were evaluated in blood (real-time PCR) and plasma (ELISA). RESULTS: mtDNA and hepcidin levels were significantly increased in OB/GDM(-) versus NW, significantly correlating with pregestational BMI. Male/female (M/F) ratio was equal in study groups, and overall F-carrying pregnancies showed significantly higher mtDNA and hepcidin levels than M-carrying pregnancies both in obese and normal weight mothers. CONCLUSIONS: Our results indicate a potential compensatory mechanism to increased obesity-related OxS and inflammation, indicated by the higher hepcidin levels found in obese mothers. Increased placental mitochondrial biogenesis, due to lipotoxic environment, may account for the greater mtDNA amount released in maternal circulation. This increase is namely related to F-carrying pregnancies, suggesting a gender-specific placental response.

Infertility as a cancer risk factor - a review.

Ovarian, endometrial and breast cancers are associated with several risk factors, such as low parity, infertility, early age at menarche, and late age at menopause. Frequently most of these risk factors coexist in infertile patients and some studies suggested that the different infertility causes can be involved in cancer risk development. In particular case-control and cohort studies investigated the possible role of ovulatory disorders, endometriosis and unexplained infertility in increasing the risk of this disease. Most studies have shown no overall increased risk in invasive ovarian cancer in subfertile patients, although nulliparity has been consistently associated with increased rates of ovarian tumor, in particular with borderline and endometrioid cancers in patients with a history of endometriosis. Different studies reported that infertile women are not at risk for breast cancer. However, women affected by infertility may be more at risk for endometrial cancer, particularly if affected by ovulatory disorders. Moreover, infertility is now often treated with medical devices that could by themselves modify the hormonal environment and be cofactors in the cellular changes towards cancer development. However, although early studies suggested that infertility medications were associated to increased risk in ovarian cancer, subsequent studies have been mainly reassuring, although suggesting that type and duration of medical treatment can increase the malignancy risk. An increased risk of endometrial cancer in patients undergoing infertility treatment has been reported, as expected by the similar structure shared by clomiphene and tamoxiphene. Since breast cancer is widely recognized as having a hormonal etiology, a possible role of fertility medications to promote cancer has been hypothesized. However, many large studies were not able to find an associated risk of breast cancer. In conclusion, nowadays, firm answers about the precise effects of infertility and its treatment on cancer risk are not available but findings are generally reassuring. Further studies about fertility drug treatments on larger populations may offer in the future longer follow-up and more precise data with better adjustments for confounding factors.

Fetal and placental chromosomal mosaicism revealed by QF-PCR in severe IUGR pregnancies.

A number of genetic and environmental factors are taken into account as responsible for intrauterine growth restriction (IUGR); nevertheless, the relevance of genetic alteration in IUGR aetiology remains to be determined. The aim of this study was to investigate using a combined cytogenetic-molecular approach, improved by a new application of QF-PCR method, the presence of mosaic chromosomal changes in fetal/placental samples from 12 pregnancies with unexplained severe IUGR. This multiple approach allowed us to reveal and quantify subtle chromosomal mosaicisms with less than 5% of trisomic cells even in cases in which cytogenetic and FISH analyses failed to reveal them. These are three pregnancies with a mosaic trisomy for chromosomes 7, 2 and 14; the former case presented matUPD7 and was previously described in this journal (Placenta 22 (2001) 813) in association with pre- and postnatal growth restriction. It is intriguing that chromosomes 7, 2 and 14 are known or suspected to harbour imprinted genes, so that an unbalanced gene dosage in a subset of cells during embryonic development could lead to an early impairment of placental function. Our findings indicate that extensive molecular and cytogenetic studies of IUGR fetal and placental tissues are necessary to reveal at least part of the heterogeneous genetic lesions implicated in IUGR phenotypes.

Fetal development after assisted reproduction--a review.

Despite the success of assisted reproduction technologies (ART) in allowing conception in couples with infertility problems, a growing body of evidence points to implication of ART on fetal birth weight alterations, fetal malformations, chromosomal aneuploidies and syndromes related to genomic imprinting modifications. Different causes can be accounted for to explain the increased risk of fetal defects. Pregnancies generated by ART differ from spontaneously achieved pregnancies in that gametes and embryos are cultured in vitro, more than one conceptus is transferred into the uterine cavity, and the time of transfer is different to what occurs in normal conditions. Epigenetic reprogramming of gene expression has been advocated in relation to the gamete and embryo manipulation, with a significant role of genomic imprinting in determining changes in fetal growth. Moreover, the maternal environment, with the ovarian hyperstimulation of the beginning of pregnancy, could alter the maternal response to the early phases of trophoblast invasion. There are suggestions that placental weights and placental/fetal weight ratios are increased in these pregnancies resembling the model of maternal undernutrition in the early phases of pregnancy. Therefore concern has also arisen around the possible long term and transgenerational effects of assisted reproduction procedures and studies should be carried out to evaluate these possibilities.