Developmental exposure to endocrine disruptor bisphenol A (BPA) is associated with metabolic defects during adulthood. In sheep, prenatal BPA treatment causes insulin resistance (IR) and adipocyte hypertrophy in the female offspring. To determine if changes in insulin sensitivity mediators (increase in inflammation, oxidative stress, and lipotoxicity and/or decrease in adiponectin) and the intracrine steroidal milieu contributes to these metabolic perturbations, metabolic tissues collected from 21-month-old female offspring born to mothers treated with 0, 0.05, 0.5, or 5 mg/kg/day of BPA were studied. Findings showed prenatal BPA in non-monotonic manner (1) increased oxidative stress; (2) induced lipotoxicity in liver and muscle; and (3) increased aromatase and estrogen receptor expression in visceral adipose tissues. These changes are generally associated with the development of peripheral and tissue level IR and may explain the IR status and adipocyte hypertrophy observed in prenatal BPA-treated female sheep.

A case of congenital cystic adenomatoid malformation of the lung is presented with prenatal ultrasound findings. The present case appears to be the third instance reported in which the diagnosis was made antenatally by ultrasound, and the first which resulted in a live birth, although the patient succumbed to pulmonary hypoplasia.

Prenatal testosterone (T)-treated female sheep manifest reduced adipocyte size and peripheral insulin resistance. The small adipocyte phenotype may reflect defects in adipogenesis and its steroidal machinery. To test whether prenatal T treatment from gestational days 30 to 90 alters the visceral adipose tissue (VAT) steroidal machinery and reduces adipocyte differentiation, we examined expression of the steroidogenic enzymes, steroid receptors, and adipocyte differentiation markers at fetal day 90 and postnatal ages 10 and 21 months. Because gestational T treatment increases fetal T and maternal insulin, the contributions of these were assessed by androgen receptor antagonist or insulin sensitizer cotreatment, either separately (at fetal day 90 and 21 months of age time points) or together (10 months of age). The effects on adipogenesis were assessed in the VAT-derived mesenchymal stem cells (AT-MSCs) from pre- and postpubertal time points to evaluate the effects of pubertal steroidal changes on adipogenesis. Our results show that VAT manifests potentially a predominant estrogenic intracrine milieu (increased aromatase and estrogen receptor α) and reduced differentiation markers at fetal day 90 and postnatal 21 months of age. These changes appear to involve both androgenic and metabolic pathways. Preliminary findings suggest that prenatal T treatment reduces adipogenesis, decreases expression of differentiation, and increases expression of commitment markers at both pre- and postpubertal time points. Together, these findings suggest that (1) increased commitment of AT-MSCs to adipocyte lineage and decreased differentiation to adipocytes may underlie the small adipocyte phenotype of prenatal T-treated females and (2) excess T-induced changes in steroidal machinery in the VAT likely participate in the programming/maintenance of this defect.

Prenatal testosterone (T)-treated sheep, similar to women with polycystic ovary syndrome (PCOS), manifests reproductive defects that include multifollicular ovarian phenotype. Women with PCOS manifest increased ovarian matrix metalloproteinases (MMPs) activity. We tested the hypothesis that gestational T excess in sheep would alter ovarian expression of MMPs, tissue inhibitors of MMP (TIMP) and their target proteins laminin B (LAMB), collagen, tumor necrosis factor alpha (TNF), and connexin 43 (GJA1) consistent with increased MMP activity and that these changes are developmentally regulated. The ovarian content of these proteins was quantified by immunohistochemistry in fetal day 90, 140, and adult (21 months of age) ovaries. Prenatal T excess lowered GJA1 protein content in stroma and granulosa cells of primary follicles from fetal day 90 ovaries and decreased stromal MMP9, TIMP1, and LAMB in fetal day 140 ovaries. In the adult, prenatal T-treatment (1) increased MMP9 in theca cells of large preantral follicles and stroma, TNF in granulosa cells of small and large preantral follicles and theca cells of large preantral and antral follicles, and GJA1 in stroma, theca cells of large preantral follicles, and granulosa cells of antral follicles and (2) reduced TIMP1 in stroma, theca cells of large preantral and antral follicles, LAMB in stroma and small prenatral follicles, and collagen content in stroma and around antral follicles. These findings suggest a net increase in MMP activity and its target proteins TNF and GJA1 in prenatal T-treated adult but not in fetal ovaries and their potential involvement in the development of multifollicular morphology.

This is the first description of an association between these two rare malformations. Although a causative link between CCAM and ACD is possible, it is unlikely. ACD should always be considered as a cause of severe PPHN when persistent beyond 10 days, even if another etiology of PPHN is present.