In-vitro study of the effect of anti-hypertensive drugs on placental hormones and angiogenic proteins synthesis in pre-eclampsia

Antihypertensive drugs lower the maternal blood pressure in pre-eclampsia (PE) by direct or central vasodilatory mechanisms but little is known about the direct effects of these drugs on placental functions

Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss

The normal menstrual cycle in women

The menstrual cycle in women is characterised by high variability in cycle length (26–35 days), 5-day menses, a fertile phase from 5 days before to the day of ovulation, and low fertility which is dependent on cycle length and age. All women show an FSH rise at the luteal–follicular transition, stimulating a cohort of follicular growth and inhibin B secretion in the early follicular phase. The ovulatory dominant follicle (DF) is selected in the mid-follicular phase, and as this DF grows it increasingly secretes oestradiol and inhibin A for a week before ovulation. Gonadotrophin responsiveness, IGF binding protein expression and degradation, and vascularisation have been identified to be crucial for DF selection and progression. Two-thirds of women show two follicle waves and 1/3 show 3 follicle waves per cycle. Three-wave women have longer cycles, and a later oestradiol rise and LH surge. The corpus luteum secretes progesterone, oestradiol and inhibin A in response to LH pulses, and reaches its peak in terms of size, secretions, and vascularization 6–7 days after ovulation. Luteal regression is passive and independent of the uterus, but can be prevented by hCG, the luteotrophic signal from the trophoblast, from 8 days after conception. Reductions in systemic steroid and protein hormone concentrations may be responsible for the FSH rise characteristic of premenopausal women. The functional layer of the endometrium shows steroid hormone-dependent proliferation, differentiation, and shedding in the absence of the trophoblast. Menstruation is initiated by progesterone responsive decidual cells, and executed by PGE and PGF2α, vasoconstriction and matrix metalloprotease secretion by leukocytes. Ovarian function and also hormone fluctuations during the menstrual cycle are similar to oestrous cycles of cows and mares, justifying research into comparative aspects of menstrual and oestrous cycles in monovulatory species