Maternal estrogen and progesterone levels after hypophysectomy in early pregnancy and in term fetuses or newborn monkeys

Pregnant rhesus monkeys ($\text{Macaca}$$\text{mulatta}$) were hypophysectomized at 8–10 weeks gestation to determine effects on plasma levels of estrone (E₁), estradiol-17β (E₂) and progesterone (P). The first group of monkeys was subsequently fetectomized At 107–114 days. After hypophysectomy there was an initial decrease in maternal peripheral plasma E₂ followed by a rise to preoperative levels within 4–5 weeks. Plasma levels of e₁ and P were not markedly altered. After fetectomy, peripheral estrogen concentrations, especially E₂, declined markedly. In the second experimental series, we have examined the effects of maternal hypophysectomy on levels of E₁, E₂ and P either (1) in both mother and newborn baby or (2) in mother, term fetus and umbilical vein. Groups of hypophysectomized and intact pregnant monkeys (3 each) were delivered by cesarean section at the expected time of parturition. Other hypophysectomized and intact monkeys (2 each) delivered normally. E₂ levels were elevated significantly in plasma of hypophysectomized monkeys at the time of cesarean delivery and in newborn babies of hypophysectomized mothers shortly after parturition. Except for these differences, the maternal hypophysis apparently is not a major factor in the control of E₁, E₂ and P concentrations in pregnant rhesus monkeys.     

Plasma estrogens,progesterone and chorionic gonadotropin in pregnant rhesus monkeys (Macaca mulatta) after ovariectomy

Maternal peripheral plasma concentrations of estrone (E₁), estradiol-17β (E₂), and progesterone (P) were determined in 4 rhesus monkey ovariectomized in early pregnancy (22–24 days). After ovariectomy, plasma concentrations of E₁ and E₂ were basal for 1 to 2 weeks. In contrast, slightly higher estrogen levels, which may be attributed to the ovaries, were found in intact pregnant monkeys. E₂ levels increased rapidly after this and exceeded those of E₁ until the 5th month of gestation. From that time until parturition, E₁ levels equaled or exceed those of E₂ in most instances. The pattern of P concentrations was similar to that observed in intact monkeys. Urinary chorionic gonadotropin (MCG) levels in ovariectomized monkeys were not significantly differen from those found in normal pregnancies. Thus, the patterns for circulating E_l, E₂ and P, as well as for the excretion of MCG,. after ovari-ectomy were remarkably similar to those found in intact, pregnant rhesus monkeys, indicating minimal ovarian influence.     

Role of the primate placenta in cortisol secretion by the maternal adrenals

Peripheral serum cortisol levels were measured throughout gestation in 5 intact pregnant rhesus monkeys (Macaca mulatta) and 3 hypophysectomized-fetectomized monkeys, leaving the placentas in situ and viable. These monkeys, as well as 4 other groups used to separately control for effects of pregnancy, hypophysectomy, or fetectomy, were unilaterally (left) adrenalectomized to permit comparisons of adrenal gland weights. Circulating cortisol levels of intact pregnant monkeys tended to rise slightly with advancing gestation. However, hypophysectomy at 70 to 73 days after fertilization caused a marked decline (p < 0.01) in serum cortisol concentrations to about 1/2 the preoperative level. These monkeys were fetectomized at 107 to 114 days without further reduction in circulating cortisol levels. In hypophysectomized-fetectomized monkeys, either surgical removal of the placentas near term or abortion was followed by a rapid decrease in peripheral cortisol to undetectable concentrations. Their cortisol levels were 5 to 12 times higher in left adrenal venous effluent than in peripheral circulation on the day of placental delivery. The presence of a viable placenta protected against the extensive adrenocortical involution seen in nonpregnant hypophysectomized monkeys (p < 0.01). Fetectomy, alone or in combination with hypophysectomy, did not alter left adrenal gland weights from those of intact pregnant monkeys. Thus, continued cortisol secretion and maintenance of adrenal weight in hypophysectomized-fetectomized monkeys, in the presence of a functional placenta, supports the existence of a placental adrenocorticotropin in this primate.     

Effect of partial fetectomy on plasma 13,14-dihydro-15-keto-prostaglandin F2α in late pregnancy of sows

The aim of this study was to ascertain if partial fetectomy in late pregnancy affected prostaglandin F_2α levels, thereby influencing the time of delivery of the remaining fetuses in the sow. Sham fetectomy or surgical removal of one, two, three or four fetal piglets was performed on each of ten sows during the last 3 weeks of pregnancy. Removal of no fetuses (two sows) and in one sow a single fetus was followed by a continuation of pregnancy to the expected time of parturition. Plasma values for oestrone, progesterone and 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) were similar to those reported previously for normal sows. Removal of one (two sows), two (two sows), three (two sows) or four (one sow) fetuses was followed by premature parturition, within 42–144 h of surgery. Labour lasted 24 to 30 h. Almost immediately after fetectomy, PGFM levels in plasma increased and were accompanied by a decline in progesterone concentrations. High PGFM values (13–60 ng/ml) were present at parturition. Oestrone concentrations were variable or rose slightly at this time. The results suggest that all fetuses in a litter must be present to maintain pregnancy to term. Pregnancy may depend upon fetal suppression of prostaglandin F_2α production and release until the appropriate time for parturition.     

Excessive ovarian follicular development in pregnant pigtailed macaques (Macaca nemestrina)

To evaluate the status and possible control of ovarian follicular development during pregnancy, circulating levels of estrone (E₁), estradiol-17β (E₂), and follicle-stimulating hormone (FSH) were measured throughout gestation in both intact and ovariectomized pregnant pigtailed monkeys (Macaca nemestrina). From an additional group of pregnant monkeys, ovaries were obtained at late gestation (on day 150 or 159 of pregnancy) for histological studies. Circulating concentrations of E₁ and E₂ increased on day 13 and remained elevated for about 10 days; they then declined and reached low levels on day 32 of gestation. After day 60, there were gradual but smaller increases in estrogen levels to day 140, after which both E₁ and E₂ levels increased significantly, reaching maximum levels (E₁ = 832.2 ± 210.8 pg/ ml; E₂ = 1.66 ± 0.32 ng/ml) at the end of pregnancy. Removal of ovaries on day 35 of gestation did not affect pregnancy or the pattern of estrogen secretion. Serum concentrations of FSH demonstrated only minor fluctuations during pregnancy but were similar to those found during the early follicular phase of cycling pigtailed monkeys investigated in this study. Ovarian histology revealed extensive follicular growth; in addition to the corpus luteum of pregnancy, ovaries were packed with pre-antral, small antral, and medium-sized Graafian follicles. Some of these follicles appeared to be cystic and showed various degree of atresia; their general appearance was similar to the follicles of human females with polycystic ovary syndrome. Our data suggest that FSH may initiate ovarian follicular growth during gestation. High levels of estrogens were incapable of suppressing FSH secretion but may be responsible for the induction of atresia in a large number of follicles in pregnant pigtailed monkeys.     

Fetectomy alters maternal pituitary-adrenal function in pregnant rhesus macaques.

The interplay between the fetus and mother may play a key role in the regulation of primate pregnancy and parturition. This study was designed to test the hypothesis that fetectomy alters maternal pituitary-adrenal function. Between 117 and 122 days of gestation (term = 167 days), six rhesus macaques underwent surgery for catheter implantation. At surgery the fetuses were removed while the membranes and placenta were left in situ. Six additional intact catheterized pregnant animals served as controls. Animals were maintained under a 12L:12D cycle with lights-on from 0700 to 1900 h. Beginning at least 1 wk after surgery, maternal arterial blood samples were collected at 3-h intervals for 24 h for hormone and catecholamine analysis. This sampling protocol was repeated at weekly intervals until cesarean delivery at 151-157 days of gestation. Following fetectomy, plasma ACTH, dehydroepiandrosterone sulfate (DHEAS), and cortisol levels were significantly lower (36%, 35%, and 44%, respectively) compared with control animals (P;lt 0.05). Despite a significant reduction in overall levels, the rhythm in maternal plasma cortisol was maintained following fetectomy. Plasma dopamine and norepinephrine were also depressed (P;lt 0.05), whereas epinephrine remained unaffected. Our data clearly demonstrate the role of the fetus in the regulation of the maternal pituitary-adrenal axis during gestation. This interaction plays a significant role in the regulation of maternal endocrine function that may influence the initiation of labor.     

Effects of PGF2α and PGF2α, 1–15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey

The effects of prostaglandin (PG)F_2α and PGF_2α, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF_2α, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF_2α or PGF_2α, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF_2α, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF_2α, 1–15 lactone. These data indicate that PGF_2α, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF_2α, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF_2α.     

17 β-hydroxysteroid dehydrogenase in monkey endometrium during the menstrual cycle and at the time of implantation

In order to further identify physiological similarities between 17β-hydroxysteroid dehydrogenase (HSD) in human and monkey endometrium, and to evaluate the role of estradiol-17β (E₂) oxidation to estrone (E₁) during periimplantation events, 30 rhesus monkeys were studied at different intervals of the nonfertile menstrual cycle (days 8, 12, 15, 18 and 24). Also, five pregnant monkeys provided endometrial tissue on day 24 of the fertile menstrual cycle, near the expected time of implantation. HSD activity in endometrium was low at midfollicular phase (day 8), increased to maximal levels (8-fold) during the periovulatory span (days 12 and 15),and was intermediate in mid to late luteal phase (days 18 and 24) in non-fertile menstrual cycles. In the absence of ovulation, HSD was low throughout. These enzyme data fit with a pattern of daily peripheral serum levels of E₂ and progesterone (P) and suggest that when the normal sequence of P follows elevated estrogens in late follicular phase, HSD activity is markedly enhanced in the early luteal phase. However, HSD activity in endometrium did not increase more in the fertile menstrual cycle, despite further elevations of serum P during rescue of the corpus luteum.     

Prostaglandin F in the peripheral plasma of the rhesus monkey in normal pregnancy and after the administration of dexamethasone and PGF2α

The concentration of prostaglandin F (PGF) has been measured in the peripheral plasma of normal rhesus monkeys ( ) during the final third of gestation, and in monkeys treated with dexamethasone or PGF₂α after day 145 of pregnancy. Daily administration of PGF₂α (10–15 mg/day im) reliably induced abortion within 3–6 days. However, dexamethasone (8 mg/day im from day 145) had no effect on the length of gestation.The concentration of PGF in the femoral venous plasma of untreated or dexamethasone-treated monkeys was highly variable, both in serial samples taken from the same animal and in samples taken from different animals at the same time of gestation. There was no indication of an effect of dexamethasone treatment on the plasma PGF levels, nor did the concentration of PGF increase during late pregnancy before spontaneous parturition. These results show that the myometrium of the pregnant rhesus monkey is highly sensitive to exogenous PGF₂α during late gestation. However, a significant increase in the peripheral plasma concentration of PGF prior to the onset of labor was not observed.     

Prepartum onset of maternal behavior in hamsters and the effects of estrogen and progesterone.

The onset of maternal behavior in pregnant hamsters was measured by presenting foster pups at 0900 and 2100 hr on Day 15 and at 0300, 0500, and 0700 hr on Day 16 and then at hourly intervals until parturition began. The occurrence of parturition was determined at each maternal test and at 0.5 hr intervals beginning at 0700 hr on Day 16. Nulliparous and primiparous animals became maternal at approximately the same time on Day 16, 2 and 6 hr prepartum, respectively, demonstrating that parturition is not essential for maternal behavior. The second experiment showed that nulliparous females injected with either 1 μg or 10 μgm estradiol-17β (E₂), 0.1 mgm progesterone (P), 10 μgm E₂ plus 0.1 mgm P, or oil at 1200 hr on Day 15 became maternal at the same time of day (0800–1000 hr) while parturition was delayed 8 hr in females receiving P. The results suggest a dissociation between the regulation of parturition and maternal care and are compared to previous research into the hormonal basis of maternal behavior in rats.     

Characterization of estrogen and progesterone receptors in monkey endometrium: methodology and effects of estradiol and/or progesterone on endometrium of castrate monkeys.

Appropriate methods for repeated surgical collection of endometrial tissue from rhesus monkeys, and characterization of cytosol and nuclear estrogen (E₂) and progesterone (P) receptors (R) are described. Tissue collection was made in the mid-luteal phase at abdominal fundal hysterotomy. Functional status of the ovaries was determined by visual inspection and RIA of E₂ and P in serum. Receptor assay procedures were devised permitting the measurement of total cytosol and nuclear receptor concentration. Sucrose density gradients of labelled cytosol were made and a 4S saturable binding component for ³H P and for ³H E₂ were found. Equilibrium dissociation constants of ³H E₂ and ³H R5020 were 2.1×10^?10M and 3.6 × 10^?9M, respectively. These binding characteristics are similar to those found in human endometrium and suggest that these surrogate primates have extensive utility in investigation of factors influencing E₂R and PR concentrations in endometrial tissue during the menstrual cycle and implantation. Simulated menstrual cycle were produced in 20 castrate monkeys by sequential treatment with estradiol and progesterone in silastic capsules. RIA of E₂ and P, and gonadotropins in peripheral serum provided assuredness of the hormonal status of each monkey under treatment. Cytosol and nuclear receptors for E₂ and P were measured in the endometrium after different intervals of the treatment. E₂ receptor (E₂R) levels were not changed during the estrogen sequence, but were lowered by progesterone therapy in both cytosol and nuclear components. Progesterone receptor (PR) synthesis in cytosol was induced by exogenous estrogen. The total concentration of PR decreased with the uptake of P by the cell; meanwhile, the ratio of cytosol to nuclear P receptors declined. These data suggest that this sequential estrogen-progesterone regimen induces the changes in E₂R and PR patterns in the endometrium of ovariectomized monkeys which occurs due to ovarian cyclicity in the normal menstrual cycle.     

Plasma levels of 13,14-dihydro-15-keto PGE2 after vaginal application of a new PGE2 film

To determine the release and absorption profile of prostaglandin E₂ from a new vaginal film formulation containing 850 μg PGE₂, serial plasma levels of 13,14-dihydro-15-keto PGE₂ were measured by radioimmunoassay in pregnant women between 16 and 18 weeks gestation. A control group, using placebo vaginal film was included in the study. There was a somewhat uniform increase in the plasma levels of the PGE₂ metabolite, reaching peak levels between 4 and 6 hours after application of the film. The findings suggest that this drug formulation could be used clinically when slow constant release of the prostaglandin is required over a period of hours such as in pre-induction cervical ripening of term pregnancy.     

Observations on progesterone production and clearance in normal pregnant and fetectomized rhesus monkeys (Macaca mulatta).

The metabolic clearance rate (MCR) and production rate (PR) of progesterone were measured in rhesus monkeys both before and during intravenous infusion of progesterone at rates which approximately doubled or tripled the peripheral plasma levels. The monkeys were normally pregnant or fetectomized and were studied during the second half of pregnancy. Raising the peripheral plasma levels did not significantly after the MCR or the PR of progesterone. We conclude that peripheral progesterone levels are not the factor which controls the PR of progesterone in rhesus monkeys.     

Differential PGE2 and cAMP production by allogeneic and syngeneic pregnant mice uteri

Prostaglandin E₂ (PGE₂) and cAMP production in allogeneic and syngeneic pregnant mice uteri, were measured in relation to the ratio of plasma estrogen/progesterone levels. PGE₂ generation by allopregnant uteri varied with the days of pregnancy. The increment of the prostanoid coincided with the increase in plasma estrogen concentration, whereas the decrement of its production was in parallel with the increment of plasma progesterone. The syngeneic pregnant uterus was unable to increase the release of PGE₂ above basal values during the whole pregnancy. The rise of PGE₂ production by the allogeneic pregnant uterus was correlated with an increase in cAMP levels. It is proposed that the pregnant mouse uterus increases its ability to release PGE₂ in response to an ovarian steroids.     

Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats

Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E₂), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E₂ in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature.     

Endocrine profiles of somatic nuclear transfer-derived pregnancies in dairy cattle

In cattle, several hormones and proteins are necessary for maintenance of a normal pregnancy that will result in a viable calf. Deviation from the normal cascade or expected profile of reproductive hormones and proteins may be associated with impairment of somatic nuclear transfer-derived pregnancies and the high rate of fetal loss. The objectives of this study were to characterize maternal plasma concentrations of pregnancy-specific protein B (PSPB), progesterone (P4), estrone sulphate (E₁S), and estradiol (E2) during the last two-thirds of pregnancy (cloned calves), and to determine associations with gestational abnormalities. Cows with cloned fetuses, produced by either commercial (N = 16) or zona-free (N = 4) cloning techniques, were compared with pregnant animals derived from traditional embryo transfer (N = 6) or AI (N = 6), at various stages of gestation (Days 80, 120, 150, 180, 210, and 240; Day 0 = estrus). Fetal well-being was monitored with ultrasonography throughout gestation. At Day 80, progesterone concentration was lower (P < 0.0001) in nuclear transfer (NT) recipients than in control groups. Mean estrone sulphate concentrations did not vary significantly between NT and control groups. At Day 150, pregnancy-specific protein B concentrations were elevated (P < 0.002) in NT cows. Estradiol concentration was higher in NT recipients than control cows throughout the study period.     

Serum steroid hormone levels in relation to the reproductive cycle ofSebastes taczanowskii andS. schlegeli

Synopsis Changes in serum steroid hormones were studied during the reproductive cycle of two viviparous rockfishes of the genusSebastes. During the annual reproductive cycle of femaleS. taczanowskii, serum levels of estradiol-17β (E₂) gradually increased from their lowest in August to maximal levels towards the end of vitellogenesis in February, and rapidly returned to low levels in pregnant females in April and May. Serum progesterone (prog) fluctuated at low levels throughout the annual reproductive cycle, while 17α, 20β-dihydroxy-4-pregnen-3-one (17α, 20β-diOHprog) levels were high during gestation in May. Serum levels of these steroids were also measured in femaleS. schlegeli at weekly intervals during late vitellogenesis, gestation and post-parturition. In pregnant females, E₂ was high during vitellogenesis, then decreased and remained low throughout gestation. The 17α, 20β-diOHprog levels were low during vitellogenesis, then rapidly increased and remained high during gestation. On the other hand, prog values remained low, with temporal peaks coinciding with the peak of 17α, 20β-diOHprog during gestation. Based on these results and the literature, it is suggested that E₂ is the most important steroid involved in vitellogenesis and that 17α, 20β-diOHprog may play an important role in final oocyte maturation and subsequent gestation.     

Confirmation of ovulation and characterization of luteinizing hormone and progesterone secretory patterns in cycling,isosexually housed Bolivian squirrel monkeys (Saimiri boliviensis boliviensis)

In the female Bolivian squirrel monkey a much greater elevation of serum estradiol (E₂) was measured after mating than that observed in similary cycling monkeys that did not mate. This raised the possibility that cycling squirrel monkeys may not ovulate during nonmated cycles To test this hypothesis, we performed laparoscopies on nine isosexually housed, cycling monkeys to observe the ovaries after the luteinizing hormone (LH) surge, which was measured by mouse interstitial cell bioassay using LER 1909-2 as the standard. Single ovulatory stigmas were identified as well demarcated, red, punctate depressions at the center of dome-shaped elevations on the ovarian surface in eight monkeys, when laparoscopically examined 9-56 hr after the LH peak. One monkey examined laparoscopically prior to the LH surge had a large translucent cystic follicle, confirming the morphology of the mature prevulatory follicle. Mean progesterone (P) concentrations fell to a nadir 1 day prior to the LH surge and then began to rise on the LH surge. Peak P levels were found 2 days after the LH surge. In the ovulating animals in which periovulatory E₂ levels were measured, no value was greater than 800 pg/ml, indicating that the presence of follicular rupture was not sufficient to account for the elevated E₂ levels observed after mating. These data confirm ovulation and follicular rupture in the absence of mating and delineate the relationship between periovulatory LH, P, and E₂ secretory patterns in cycling squirrel monkeys.     

Effect of genistein on steroid hormone production in the pregnant rhesus monkey.

Genistein is a phytoestrogen found in soy beans. Phytoestrogens have been reported to cause reproductive problems in sheep and rats. This research was conducted to determine the effects of genistein fed to rhesus monkeys during pregnancy, with specific interest on fetal growth and steroidogenesis in the maternal-fetoplacental unit. Two groups of five monkeys each were selected in early stages of pregnancy. One group was administered genistein in a fruit treat each weekday until Cesarean section 10 days prior to term. The second, control group, received fruit treats without genistein. Maternal blood samples were collected on Tuesday and Friday of each week. At delivery, samples were collected from the maternal peripheral circulation, uterine veins, uterine-ovarian veins, and the fetal heart. Comparisons between control and genistein-treated monkeys revealed no differences in the maternal weight gained during pregnancy, or in fetal weights or placental weights at delivery. Serum was assayed by radioimmunoassay (RIA) for estradiol, progesterone, dehydroepiandrosterone sulfate (DHEA-S), and estrone. No significant differences (P > 0.05) were noted in progesterone or DHEA-S levels at delivery or during the pregnancy; however, estradiol levels were higher (P < 0.05) in the four areas studied at delivery and in the maternal blood with advancing gestation. Additionally, estrone levels tended to increase more rapidly (P = 0. 057) in the maternal blood of monkeys receiving genistein than in untreated controls, suggesting that genistein may stimulate the deconjugation of estrone in the gut, thus allowing its reabsorption into the peripheral circulation and conversion to estradiol.     

Gestation Dependant Changes in Angiogenic Factors and Their Associations with Fetal Growth Measures in Normotensive Pregnancy

Background

Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight.

Method

Ninety two pregnant women were followed at three different time points: 16–20 weeks, 26–30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits.

Results

Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight.

Conclusion

Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16–20 weeks) may be predictive of birth weight in healthy term pregnancies.