Three medicinal plants affecting human ovarian cell viability, hormone release, and response to environmental contaminant toluene.

The present study examined the effect of medicinal plants - ginkgo, tribulus (puncture vine), and yucca - on ovarian functions and their response to the toxic influence of toluene. Therefore, we analyzed the effect of toluene with and without these plant extracts on cultured human ovarian granulosa cells. Cell viability and the release of progesterone, insulin-like growth factor I (IGF I), oxytocin, and prostaglandin F (PGF) were analyzed using the trypan blue test, enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. The ginkgo, tribulus and yucca were able to suppress ovarian cell viability and alter the release of hormones. Toluene suppressed cell viability and the release of PGF, but not of progesterone, IGF-I, or oxytocin. The negative effect of toluene on cell viability was prevented and even reversed by ginkgo and yucca, whereas its effect on PGF was prevented or inverted by all tested plant extracts. These findings (1) demonstrated the direct toxic effect of toluene on ovarian cells, (2) showed the direct effect of some medicinal plants on ovarian cell functions, and (3) demonstrated the ability of these plants to inhibit the effects of toluene and to act as natural protectors against the suppressive effect of toluene on female reproduction.

Prenatal exposure to acrylamide differently affected the sex ratio, aromatase and apoptosis in female adult offspring of two subsequent generations.

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

Fennel affects ovarian cell proliferation, apoptosis, and response to ghrelin.

The objective of this study was to examine the direct effects of the medicinal plant fennel (Foeniculumvulgare Mill.) on basic functions of ovarian cells, including proliferation, apoptosis, and response to the physiological hormonal stimulator, ghrelin. In the first series of experiments, porcine ovarian granulosa cells were cultured with (1, 10, 100 µg/ml) or without fennel extract. In the second series of experiments, cells were cultured with (1, 10, 100 ng/ml) or without ghrelin, alone or in combination with fennel extract (10 µg/ml). Expression of the proliferation marker, PCNA, and the apoptosis marker, bax, were analyzed via quantitative immunocytochemical methods. Fennel stimulated the accumulation of the proliferation marker, and suppressed the expression of the apoptosis marker. Ghrelin alone promoted proliferation and apoptosis of ovarian cells. The presence of fennel inhibited these ghrelin effects. These observations provide the first demonstration of (1) effects of fennel on farm animal reproduction, (2) direct effects of fennel on ovarian cells, (3) the ability of fennel to promote ovarian cell proliferation, to inhibit ovarian cell apoptosis, and to enhance the ovarian cell proliferation:apoptosis ratio. Furthermore, our results (4) confirm the involvement of ghrelin in the control of ovarian cell apoptosis and proliferation, and (5) demonstrate the ability of fennel to affect not only ovarian cell proliferation and apoptosis, but also to suppress the responses of ovarian cells to the upstream hormonal regulator ghrelin. Our results indicate the potential applicability of fennel as a bio-stimulator of farm animal reproduction.

Effects of ferroelectric oxides of barium strontium titanate (Ba0.85Sr0.15TiO3) nanoparticles on Ruditapes decussatus assessed through chemical, physiological, and biochemical methods.

Here, the effects of a newly designed ferroelectric oxide synthesized by solid reaction, barium strontium titanate [BST (85/15)] (Ba0.85Sr0.15TiO3), on the carpet shell clam Ruditapes decussatus were investigated. These clams were exposed to four concentrations of BST (85/15) nanoparticles (0.001, 0.01, 0.1, and 1 mg.L-1), and BST (85/15) was absorbed by R. decussatus in an exposure intensity-dependent manner. Measurements of clearance rate and biomarkers confirmed that the nanoparticles significantly affected the health of clams in an organ-dependent manner. Interestingly, BST (85/15) nanoparticles stimulated acetylcholinesterase (AChE) activity in the clams, suggesting their usefulness as antagonists of AChE inhibiting pollutants. These findings demonstrate the suitability of R. decussatus as a test organism to provide a framework for understanding the toxicological effects of these newly designed ferroelectrics. Moreover, concentrations of BST (85/15) < 0.1 mg.L-1 could be good alternatives to lead-based ferroelectric oxides and could be sustainable tools for use in electronic applications.

The Action of Benzene, Resveratrol and Their Combination on Ovarian Cell Hormone Release.

The aim of our study was to examine the direct influence of plant polyphenol resveratrol and oil-related environmental contaminant benzene on ovarian hormone release, as well as the ability of resveratrol to prevent the effect of benzene. Porcine ovarian granulosa cells were cultured with and without resveratrol (0, 1,10 or 100 ug/ml) alone or in combination with 0.1% benzene. The release of progesterone, oxytocin and prostaglandin F was measured by enzyme immunoassay (EIA). Benzene promoted the release of progesterone, oxytocin and prostaglandin F. Resveratrol, when given alone, stimulated both progesterone and prostaglandin F, but not the oxytocin output. Moreover, resveratrol prevented and even inverted the stimulatory action of benzene on all analysed hormones. These observations demonstrate the direct influence of both benzene and resveratrol on porcine ovarian hormone release, as well as the ability of resveratrol to prevent the benzene action on the ovary.

The inhibitory influence of toluene on mare ovarian granulosa cells can be prevented by fennel.

The influence of environmental contaminant toluene and of plant fennel (Foeniculum vulgare Mill.) on reproduction are reported, but the mechanisms of their action and the protective effect of fennel on contaminant influence remain to be elucidated. In this study, we hypothesized that toluene and fennel directly affects basic ovarian cell functions, and that fennel can be used as an appropriate natural protective agent against the potential adverse effects of toluene. This study aimed to examine the action of toluene (20 µg/mL) and fennel extract (0, 1, 10, 100 µg/mL), and assess their combination on viability, proliferation, apoptosis, and hormone release by cultured healthy mare ovarian granulosa cells. Viability, proliferation (percentage of PCNA-positive cells), apoptosis and release of progesterone, oxytocin and prostaglandin F were evaluated by using Trypan blue exclusion tests, immunocytochemistry and enzyme immunoassays, respectively. Toluene, when given alone, inhibited viability, proliferation, apoptosis, progesterone, prostaglandin F and IGF-I. However, it did not affect oxytocin release. Moreover, Fennel, when given alone, inhibited viability, progesterone, and prostaglandin F release, as well as stimulating proliferation and oxytocin release. In addition, Fennel did not affect apoptosis. When given in combination with toluene, fennel was able to suppress, and even invert, the effects of toluene on viability, proliferation, apoptosis, prostaglandin F, and IGF-I. However, it did not alter its effect on progesterone release. Moreover, fennel induced the inhibitory effect of toluene on oxytocin output. The findings of our study suggest direct adverse effects of toluene on the basic ovarian functions of mares. Lastly, we also observed the direct influence of fennel on these functions, as well as its ability to be a natural protector against the action of toluene on the ovarian functions of mares.

The phytoestrogen, diosgenin, directly stimulates ovarian cell functions in two farm animal species.

The present in vitro study was conducted to examine the direct action of the plant steroidal sapogenin, diosgenin, on basic farm animal ovarian cell functions. As models, we used cultured porcine ovarian granulosa cells, porcine whole follicles, and rabbit ovarian fragments. The effects of diosgenin (0, 1, 10, or 100 µg/mL medium) on the markers of proliferation, cytoplasmic apoptosis, steroid (progesterone: P4, testosterone: T, and estradiol: E2) release, and peptide hormone (insulin-like growth factor I: IGF-I) release were analyzed by quantitative immunocytochemistry and radioimmunoassay. Diosgenin promoted proliferation, apoptosis, and T and E2 release and inhibited P4 output in cultured porcine granulosa cells. Similarly, cultured porcine ovarian follicles showed diosgenin-induced inhibition of P4 and stimulation of T release. In cultured rabbit ovarian fragments, diosgenin stimulated P4 and IGF-I release. This is the first study showing that diosgenin can promote basic ovarian cell functions such as proliferation, apoptosis, and steroid and peptide hormone release. The similar effects of diosgenin on porcine granulosa cells and ovarian follicles suggest that granulosa cells are the primary ovarian target of diosgenin. The contrasting effects of diosgenin on porcine and rabbit ovarian P4 output suggest that diosgenin functions in a species-specific manner. These observations indicate that diosgenin has potential applications for improving female reproduction.

Cow body condition affects the hormonal release of ovarian cells and their responses to gonadotropic and metabolic hormones.

The body condition score (BCS) of cows affects their reproductive efficiency, but the underlying mechanism is unclear. We examined the effect of BCS on the basic ovarian cell functions and their responses to gonadotropic and metabolic hormones. We isolated ovarian cells from cows with a tendency toward emaciation (BCS2) and those with an average body condition (BCS3), and we compared their hormonal release and responses to FSH, leptin, ghrelin, and neuropeptide Y (NPY) added at doses of 0, 1, 10, or 100 ng/mL. Progesterone, testosterone, estradiol, and insulin-like growth factor I (IGF-I) release were evaluated by RIA. No differences were found in progesterone or testosterone release between BCS2 and BCS3 cells; however, ovarian cells from BCS2 cows released more estradiol and IGF-I than cells from BCS3 cows. FSH, ghrelin, and NPY promoted progesterone release in BCS2 cells but had no stimulatory or inhibitory effect on BCS3 cells. In contrast, leptin promoted progesterone release in BCS3 cells and inhibited progesterone release in BCS2 cells. FSH also promoted testosterone release in both BCS2 and BCS3 cells but inhibited progesterone at a low dose in BCS3 cells. Leptin inhibited testosterone release in BCS3 cells but not in BCS2 cells. Estradiol release was promoted by leptin and ghrelin in BCS3 cells; however, it was unaffected by leptin and inhibited by ghrelin in BCS2 cells. IGF-I production was promoted by FSH and inhibited by leptin in both groups. Ghrelin suppressed IGF-I release in BCS2 cells and increased IGF-I release in BCS3 cells. NPY promoted IGF-I release in BCS2 cells but not in BCS3 cells. Our results demonstrate the effects of BCS on ovarian cell estradiol and IGF-I (but not progesterone or testosterone) release, as well as on the responses of ovarian cells to FSH, leptin, ghrelin, and NPY.

cAMP response element-binding protein 1 controls porcine ovarian cell proliferation, apoptosis, and FSH and insulin-like growth factor 1 response.

The aim of the present study was to examine the role of cAMP response element-binding protein (CREB) and its phosphorylation in the regulation of ovarian cell proliferation and apoptosis, and of the response of proliferation and apoptosis to the upstream hormonal stimulators FSH and insulin-like growth factor (IGF) 1. In the first series of experiments, porcine ovarian granulosa cells, transfected or not with a gene construct encoding wild-type CREB1 (CREB1WT), were cultured with and without FSH (0, 1, 10 or 100ngmL-1). In the second series of experiments, these cells were transfected or not with CREB1WT or non-phosphorylatable mutant CREB1 (CREB1M1) and cultured with and without FSH (0, 1, 10 or 100ngmL-1) or IGF1 (0, 1, 10 and 100ngmL-1). Levels of total and phosphorylated (p-) CREB1, proliferating cell nuclear antigen (PCNA), a marker of proliferation, and BAX, a marker of apoptosis, were evaluated by western immunoblotting and immunocytochemical analysis. Transfection of cells with CREB1WT promoted accumulation of total CREB1 within cells, but p-CREB1 was not detected in any cell group. Both CREB1WT and CREB1M1 reduced cell proliferation and apoptosis. Addition of 10 and 100ngmL-1 FSH to non-transfected cells promoted CREB1 accumulation and apoptosis, whereas cell proliferation was promoted by all concentrations of FSH tested. FSH activity was not modified in cells transfected with either CREB1WT or CREB1M1. IGF1 at 100ngmL-1 promoted cell proliferation, whereas all concentrations of IGF1 tested reduced apoptosis. Transfection with either CREB1WT or CREB1M1 did not modify the effects of either FSH or IGF1, although CREB1M1 reversed the effect of IGF1 on apoptosis from inhibitory to stimulatory. These observations suggest that CREB1 is involved in the downregulation of porcine ovarian cell proliferation and apoptosis. The absence of visible CREB1 phosphorylation and the similarity between the effects of CREB1WT and CREB1M1 transfection indicate that phosphorylation is not necessary for CREB1 action on these processes. Furthermore, the observations suggest that FSH promotes both ovarian cell proliferation and apoptosis, whereas IGF1 has proliferation-promoting and antiapoptotic properties. The effect of FSH on CREB1 accumulation and the ability of CREB1M1 to reverse the effects of IGF1 on apoptosis indicate that CREB1 is a mediator of hormonal activity, but the inability of either CREB1WT or CREBM1transfection to modify the primary effects of FSH and IGF1 suggest that CREB1 and its phosphorylation do not mediate the action of these hormones on ovarian cell proliferation and apoptosis.

A new model for fetal programming: maternal Ramadan-type fasting programs nephrogenesis.

The effect of maternal Ramadan-type fasting (RTF) on the outcome of pregnancy, kidney development and nephron number in male rat offspring was investigated in current study. Pregnant rats were given food and water ad libitum during pregnancy (control) or restricted for 16 h per day (RTF). Kidney structure was examined during fetal life, at birth, and in early and late adulthood. Maternal body weight, food intake, relative food intake and plasma glucose levels were significantly lower (P<0.001) in the RTF group. Litter and pup weights also were significantly lower (P<0.05) in the RTF group at birth, with no difference in the litter size. The RTF group had a longer gestation, delayed nephrogenesis with less well-differentiated glomeruli, more connective tissue, fewer medullary rays, an increase in the nephrogenic zone/cortical zone ratio, and significant increase (P<0.001) in kidney apoptosis at birth. On the other hand, maternal fasting reduced nephron number (by ~31%) with unchanged kidney and total glomerular volumes. Mean glomerular volume was significantly higher in RTF offspring. Assessment of renal structure revealed mild glomerulosclerosis with enlarged lobulated glomeruli in the renal cortex and high interstitial fibrosis in the medulla of RTF kidneys. Taken together, gestational fasting delays nephrogenesis and reduces nephron number in the kidneys of the offspring, that could be partially owing to increased apoptosis.

ß-Catenin accumulation and S33F mutation of CTNNB1 gene in colorectal cancer in Saudi Arabia.

Several risk factors associated with colorectal cancer (CRC) have been identified including ß-catenin/CTNNB1 hotspot mutations. The levels of ß-catenin within a cell are regulated via phosphorylation of the N terminus of ß-catenin by GSK-3ß. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3ß phosphorylation. In the present investigation an attempt was made to study the role of ß-catenin mutations in exon-3 in 60 colorectal cancer patients from Kingdom of Saudi Arabia (KSA). The hot spot mutation region of ß-catenin exon 3 was evaluated in matched tumor and normal tissues using PCR and direct sequencing. Sequencing of exon 3 of the CTNNB1 gene revealed an activating mutation (S33F) in one of the tumor samples as compared to the normal tissue from the same patient where there was no such mutation found. Immunohistochemical staining showed the accumulation of ß-catenin protein both in cytoplasm and in the nuclei of cancer cells as compared to normal tissue.

A randomized trial of Boswellia in association with betaine and myo-inositol in the management of breast fibroadenomas.

OBJECTIVE: Breast fibroadenoma is a common finding in young women and actually accounts for the majority of benign breast lumps. Fibroadenoma does not require any treatment unless clinical symptoms (mostly mastalgia) or histological markers of cancer risk (atypia) impose specific medical or surgical intervention. In symptomatic fibroadenoma, anti-estrogenic treatments provided evidence of success. Yet, these therapies are often associated with relevant side effects that lead to drug treatment discontinuation. Additionally, in such cases, relapse is a frequent issue. Therefore, an optimal strategy is still warranted. Boswellia, betaine and myo-inositol have already been proved to modulate different pathways - inflammatory, metabolic, oxidative and endocrine processes - in a wide array of human tissues. Based on that background, we hypothesized that these substances can effectively synergize in inducing the regression of fibroadenoma. PATIENTS AND METHODS: We included 64 patients ≤ 30 years of age with fibroadenoma. The patients were randomized into two groups. The experimental group was treated with an association of Boswellia, betaine, myo-inositol, B-group vitamins and N-acetylcysteine for 6 months; otherwise, the placebo group was treated only with B-group vitamins and N-acetylcysteine. Patients were monitored at the enrollment and the end of the study for evaluating the clinical response. RESULTS: A significant clinical improvement was observed in the experimental arm. Fibroadenoma median volume reduction averaged 17.86% in the experimental group and 5.96% in the placebo group. Moreover, 14 out of 36 (38.88%) patients showed a reduction of fibroadenoma volume compared to 5/28 (17.85%) observed in the placebo group (p = 0.005). CONCLUSIONS: A supplementation with Boswellia, betaine and myo-inositol reduces fibroadenoma dimension in young women. No relevant side effects have been recorded.

An association of boswellia, betaine and myo-inositol (Eumastós) in the treatment of mammographic breast density: a randomized, double-blind study.

OBJECTIVE: Mammographic breast density is a recognized risk factor for breast cancer. The causes that lead to the proliferation of the glandular breast tissue and, therefore, to an increase of breast density are still unclear. However, a treatment strategy to reduce the mammary density may bring about very relevant clinical outcomes in breast cancer prevention. Myo-inositol is a six-fold alcohol of cyclohexane, has already been proved to modulate different pathways: inflammatory, metabolic, oxidative and endocrine processes, in a wide array of human diseases, including cancer and the genesis of mammary gland and breast diseases, like fibrosis, as well as metabolic and endocrine cues. Similarly, boswellic acid and betaine (three-methyl glycine) both inhibit inflammation and exert protective effects on breast physiology. Based on this scientific background, we hypothesized that a combination including, boswellic acid, betaine and myo-inositol would be able to reduce breast density working on different pathways. PATIENTS AND METHODS: In this study, seventy-six premenopausal women were randomly assigned to the placebo and the experimental drug arms (Eumastós) for six months. RESULTS: After 6 months of treatment, statistically significant difference between the two groups was recorded on the breast density reduction (60% vs. 9%), using mammographic as well as ultrasound examination. CONCLUSIONS: Preliminary data collected here with support the starting assumptions, that the association comprising boswellic acid, betaine and myo-inositol significantly reduces mammary density, providing the first evidence for a new and safe approach for the management of mammographic density treatment.

Genetic association between the HLA-G 14-bp insertion/deletion polymorphism and the recurrent spontaneous abortions in Saudi Arabian women.

The non-classical class I human leukocyte antigen (HLA)-G molecule was found to be predominately expressed in the extravillous cytotrophoblasts at the fetal-maternal interface during pregnancy. This molecule is critically important for successful implantation during human pregnancy. The polymorphic insertion-deletion (indel) 14-base pair (bp) site localized at the 3' untranslated region was associated with HLA-G mRNA stability and isoform alternative splicing patterns, and thus may influence HLA-G function during pregnancy. We studied the association between the 14-bp indel polymorphism (rs16375) at the 3' untranslated region with recurrent spontaneous abortions in a Saudi population living in Riyadh. A group of 64 women with 2-11 successive abortions were included in this study. The control group included 62 women without reported abortions and at least 2 pregnancies, all visiting the King Khaled Hospital in Riyadh. The 14-bp indel was genotyped in the case and control groups. The frequency of the genotype +14/+14 was slightly higher in women with recurrent spontaneous abortions, but no significant differences were observed in the distribution of alleles and genotypes.

Sex differences in regional specialisation across the placental surface.

There may be regional specialisation in structure and function across the placental surface. In Riyadh, Saudi Arabia, the length and the breadth of the placental surface at birth were highly correlated, but the breadth was more closely associated with the size of the baby. To replicate this we studied 321 pregnant Saudi women in the town of Baish. We measured the size of the newborn babies and their placentas. The association of the length and breadth of the placental surface on the baby's body size differed in boys and girls. Among boys the breadth had a stronger association with all birth measurements except crown-heel length. This was similar to the findings in Riyadh. Placental surface length was related to crown-heel length. For each centimetre in surface length, crown-heel length increased by 0.27 cm (95% CI 0.09-0.44, p = 0.004). Among girls placental surface breadth was related to crown-heel length, whereas surface length was related to birth weight, head and thigh circumferences. For each centimetre in surface breadth, crown-heel length increased by 0.33 cm (0.13-0.53, p = 0.001). We conclude that, within Saudi Arabia, there are both geographical and sex differences in regional specialisation across the placental surface. In the adverse circumstances of Baish, linked to the mothers' short stature, boys were smaller at birth than girls. Boys may have compensated for under-nutrition by increasing the depth of spiral artery invasion rather than by recruiting additional spiral arteries. Girls may have had more effective regional specialisation across the placental surface.

Intergenerational effects of in utero exposure to Ramadan in Tunisia.

UNLABELLED: We have reported that changes in the lifestyle of pregnant women during Ramadan affect more than one generation. In a series of newborn babies in Saudi Arabia, those whose mothers had been in utero during Ramadan differed from those whose mothers had not been in utero during Ramadan. These were unexpected findings and require replication. METHODS: We examined body size at birth in 1,321 babies (682 boys and 639 girls) born in Gafsa, a small city in Tunisia. RESULTS: Babies whose mothers had been in utero during Ramadan were smaller and thinner, and had smaller placentas, than those whose mothers had not been in utero during Ramadan. After adjustment for sex, the babies were 93 g lighter (95% confidence interval, 32-153, P=0.003) than those whose mother had not been in utero during Ramadan, their mean ponderal index was 0.52 kg/m(3) lower (0.24-0.79, P<0.001) and their placental weight was 21 g lower (5-37, P=0.01). The findings did not differ by trimester of maternal exposure to Ramadan. They were similar in boys and girls and in primiparous and multiparous mothers CONCLUSION: This study provides further evidence that changes in lifestyle during Ramadan have intergenerational effects.

An ultrastructural study of oogenesis and cell dynamics during cocoon shell secretion in the subterranean freshwater planarian Dendrocoelum constrictum (Platyhelminthes, Tricladida).

The ultrastructure of the ovary and the female atrium during cocoon formation was investigated in the subterranean freshwater planarian Dendrocoelum constrictum. In the peripheral portion of the ovary, the oogonia are recognized as undifferentiated germ cells, which are morphologically similar to neoblasts that have a high nucleus/cytoplasm ratio. Oocyte maturation is characterized by a marked growth of the cytoplasm because of the accumulation of cytoplasmic organelles and inclusions. The Golgi complexes begin to increase within the ooplasm and produce vesicles with an electron-dense content that fuse to produce larger spherical globules with homogeneous and electron-dense material. In the mature oocyte, the spherical globules migrate toward the cortical ooplasm, forming a continuous monolayer. We confirm that these spherical globules, which represent cortical granules rather than eggshell globules, vary in size up to 2µm and their electron-dense content shows concentric thin bands. After leaving the ovary through the oviduct, the mature and fertilized oocytes reach the female atrium where they are packaged with thousands of vitelline cells in the cocoon shell. Based on our ultrastructural analysis, we demonstrate that the wall of the cocoon shell is composed of two layers, each of which has a different origin. The shell granules extruded from the vitelline cells are involved in the secretion of the inner layer of the cocoon shell, whereas the outer layer of the cocoon shell is synthesized by the epithelial cells in the genital atrium.

The breadth of the placental surface but not the length is associated with body size at birth.

Studies of pregnancies complicated by preeclampsia led to the suggestion that the surface of the placenta is aligned along two axes, measured by its breadth and length. It was hypothesised that tissue along the breadth serves as a nutrient sensor, responding to the mother's nutritional state and fetal nutritional demands, while tissue along the length has different functions. To develop this hypothesis we measured the breadth and length of the placental surface in 401 neonates born in the King Khalid Hospital, Riyadh, Saudi Arabia, and related these measurements to the baby's body size. The breadth and length of the placental surface were highly correlated (coefficient = 0.7). Nevertheless, in a simultaneous regression with both measurements, only the breadth was associated with neonatal body size. There were strong trends of increasing birth weight, ponderal index, and the circumferences of the head, chest, abdomen and thigh with increasing placental breadth. In contrast no measurement of baby's body size was related to placental length. Birth weight increased by 125 g per cm increase in placental breadth (95% confidence interval 88 to 162, p < 0.001) but only by 20 g per cm increase in placental length (-13 to 53, p = 0.2). The corresponding figures for head circumference were 0.28 cm (0.17-0.39, p < 0.001) and 0.03 (-0.07 to 0.14, p = 0.5). The associations between placental breadth and neonatal body size were strongest if the mother's height was below the median (157 cm). The associations between a larger breadth of the placental surface and a larger baby are consistent with the hypothesis that tissue along the breadth plays a key role in nutrient transfer from mother to baby. Mothers who are short in stature are known to have lower rates of protein turnover in pregnancy. In these circumstances the ability of the placenta to transfer amino acids to the fetus may be critical.

Sex differences in birth size and intergenerational effects of intrauterine exposure to Ramadan in Saudi Arabia.

OBJECTIVES: In Europe, boys and girls have different body proportions at birth. We examined newborn babies in Saudi Arabia to determine the sex differences and whether fetal growth differed if the mother was in utero during Ramadan. METHODS: We examined body size at birth among 967 babies (479 boys and 488 girls) born in Unizah, a small city in Saudi Arabia. RESULTS: Large head circumference was the strongest single predictor of male sex. In a simultaneous regression, female sex was predicted by small head circumference (P < 0.001), low birth weight (P = 0.002), and large chest circumference (P = 0.008). The mothers of boys were heavier in pregnancy than the mothers of girls and had a higher body mass index, 31.7 kg/m(2) compared to 30.2 (P < 0.001). The mothers of girls, however, were taller than the mothers of boys, 158.6 cm compared to 157.4 (P = 0.001). Compared to babies whose mothers were not in utero during Ramadan boys whose mothers were in mid gestation during Ramadan were 1.2 cm longer (P = 0.005) while girls had a 0.4 week shorter gestation period (P = 0.04). CONCLUSION: Our findings are consistent with other evidence that boys are more ready than girls to trade off visceral development in utero to protect somatic and brain growth. They also support the hypothesis that boys are more responsive to their mother's current diet than girls, who respond more to their mother's life time nutrition and metabolism. They provide the first evidence that changes in the life style of pregnant women during Ramadan affect more than one generation.