Serap Simavli

Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone.

The adipocyte-derived hormone leptin plays a critical role in the central transmission of energy balance to modulate reproductive function. However, the neurocircuitry underlying this interaction remains elusive, in part due to incomplete knowledge of first-order leptin-responsive neurons. To address this gap, we explored the contribution of predominantly inhibitory (GABAergic) neurons versus excitatory (glutamatergic) neurons in the female mouse by selective ablation of the leptin receptor in each neuronal population: Vgat-Cre;Leprlox/lox and Vglut2-Cre;Leprlox/lox mice, respectively. Female Vgat-Cre;Leprlox/lox but not Vglut2-Cre;Leprlox/lox mice were obese. Vgat-Cre;Leprlox/lox mice had delayed or absent vaginal opening, persistent diestrus, and atrophic reproductive tracts with absent corpora lutea. In contrast, Vglut2-Cre;Leprlox/lox females exhibited reproductive maturation and function comparable to Leprlox/lox control mice. Intracerebroventricular administration of kisspeptin-10 to Vgat-Cre;Leprlox/lox female mice elicited robust gonadotropin responses, suggesting normal gonadotropin-releasing hormone neuronal and gonadotrope function. However, adult ovariectomized Vgat-Cre;Leprlox/lox mice displayed significantly reduced levels of Kiss1 (but not Tac2) mRNA in the arcuate nucleus, and a reduced compensatory luteinizing hormone increase compared with control animals. Estradiol replacement after ovariectomy inhibited gonadotropin release to a similar extent in both groups. These animals also exhibited a compromised positive feedback response to sex steroids, as shown by significantly lower Kiss1 mRNA levels in the AVPV, compared with Leprlox/lox mice. We conclude that leptin-responsive GABAergic neurons, but not glutamatergic neurons, act as metabolic sensors to regulate fertility, at least in part through modulatory effects on kisspeptin neurons.

The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction.

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r(-/-) mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.

Substance P Regulates Puberty Onset and Fertility in the Female Mouse

Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1(-/-) mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice.

Effect of music therapy during vaginal delivery on postpartum pain relief and mental health

BACKGROUNDnChildbirth is an important experience in a womans life, and unfavorable birth experiences have been shown to negatively impact postpartum maternal health. Aim of this study was to evaluate the effects of music therapy on postpartum pain, anxiety level, satisfaction and early pospartum depression rate.nnnMETHODSnTotally 161 primiparous women were recruited and randomized either music group (n=80) or a control group (n=81). Women in the music group listened to self-selected music during labor. Postpartum pain intensity, anxiety level and satisfaction rate were measured using the visual analog scale (VAS), postpartum depression rate was assessed with Edinburg Postpartum Depression Scale (EPDS) at postpartum day one and day eight.nnnRESULTSnMothers in the music therapy group had a lower level of postpartum pain and anxiety than the control group and it was statistically significant at all time intervals (1, 4, 8, 16 and 24h, p<0.001). A significant difference was observed between the two groups in terms of satisfaction rate (p<0.001) and postpartum depression rate at postpartum day one and day eight (p<0.05).nnnLIMITATIONSnWe only measured the effect of music therapy on early postpartum depression rate. Effect of music on late postpartum depression rate should be investigated in future.nnnCONCLUSIONSnUsing music therapy during labor decreased postpartum anxiety and pain, increased the satisfaction with childbirth and reduced early postpartum depression rate. Music therapy can be clinically recommended as an alternative, safe, easy and enjoyable nonpharmacological method for postpartum well-being.

Hepcidin, iron status, and inflammation variables among healthy pregnant women in the Turkish population

Abstract Purpose: To investigate hepcidin levels in each trimester and their association with other haematological variables and inflammation markers during normal pregnancy among low-risk pregnant women in rural Turkey. Method: The series comprised 103 healthy Turkish primigravida women with a normal pregnancy. Blood samples were obtained at 11–14, 24–28 and 30–34 weeks of gestation. Haemoglobin, hematocrit, red cell indices, white blood cell count, platelet count, iron status indicators (plasma iron, transferrin, ferritin levels and iron binding capacity), serum hepcidin, interleukin-6 and C-reactive protein levels were analysed. The proportions were compared using Pearson’s χ2 test or Friedman’s test. Results: The mean serum hepcidin concentrations at 11–14, 24–28 and 30–34 weeks of gestation were as follows: 7.8u2009±u20093.4u2009ng/mL, 8.6u2009±u20093.1u2009ng/mL and 7.3u2009±u20093.0u2009ng/mL, respectively. The mean serum ferritin concentrations with median values at each trimester were 14.2 (11.5), 9.5 (8.8) and 11.2 (9.3), respectively. The mean serum CRP values at each trimester were 5.1 (4.0), 5.5 (4.6) and 6.0 (5.5), respectively. The serum hepcidin levels were not related to iron status or the haemoglobin, IL-6 or C-reactive protein levels. Conclusions: There was no association between serum hepcidin and serum ferritin, IL-6 or CRP concentrations in each trimester among low-risk pregnant women.

The role of gel application in decreasing pain during speculum examination and its effects on papanicolaou smear results

PurposeThis study aimed to investigate the effects of water-based gel application in reducing pain or discomfort associated with speculum examination, and compared the presence of unsatisfactory Papanicolaou smear results between gel-applied and control groups.MethodsIn this prospective randomized controlled study, a total of 1,580 patients were analyzed. The subjects were randomized to a gel group and a control group. For the collection of the smear sample, water-based gel was used in the gel group and dry speculum was used in the control group. All patients were asked to score their pain on a numeric pain scale at two time points during the procedure (insertion and opening phase of speculum). Cytopathologists who analyzed the smear cytology were blinded to the study. Pain intensity during speculum examination, as well as unsatisfactory smear results, were analyzed between the groups.ResultsThe pain scores obtained at two different time points of speculum application were significantly lower in the gel group compared to the control group both in premenopausal and postmenopausal women (pxa0<xa00.001). The ratios of unsatisfactory cytopathologic examination results were 1.13 and 1.39xa0% for the gel-applied and control groups, which were not significantly different.ConclusionLubrication of the outer superior and inferior blade of the plastic vaginal speculum with a small amount of a water-soluble lubricant gel decreases the pain associated with insertion and opening of the vaginal speculum in both premenopausal and postmenopausal women without affecting the quality of the cytology results during the collection of Papanicolaou test specimens.

Is the level of maternal serum prohepcidin associated with preeclampsia

Objective: The objective of the study was to compare pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), C-reactive protein (CRP), IL-6 and iron status parameters in preeclamptic (PE) and healthy pregnant women, and to examine the relationship between serum pro-hepcidin levels and iron parameters of preeclampsia (PE). Methods: In a prospective controlled study, we collected serum from women with normal pregnancy (nu2009=u200937) and from women with PE (nu2009=u200930) at the Department of Obstetrics and Gynecology at Turgut Ozal University between February 2010 and January 2013. Pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), CRP, IL-6 and iron status parameters were measured in all patients and compared between groups. Results: Levels of serum prohepcidin in PE and control groups were similar and amount 69.4u2009±u200919.7 and 71.9u2009±u200922.1u2009ng/ml, respectively. The difference was not statistically significant (p: 0.694). On the other hand, the study group had a statistically lower iron binding capacity (IBC), total iron binding capacity, transferin, total protein, albumin levels (pu2009<u20090.05). No significant differences were found among prohepcidin, Hb concentration, Hct, iron, ferritin, IL-6, urea and creatine in both the groups. Conclusion: In pregnancies complicated by PE with normal values of hemoglobin and hematocrit, serum prohepcidin concentrations are similar to those observed in healthy pregnant women. The analysis revealed no significant correlations between prohepcidin level and serum iron, serum ferritin or transferrin in the PE.

The impact of copper-containing and levonorgestrel-releasing intrauterine contraceptives on cervicovaginal cytology and microbiological flora: A prospective study

Abstract Objective To compare vaginal microflora and cervical cytology before and after insertion of a copper-containing intrauterine device (Cu-IUD) or a levonorgestrel releasing-intrauterine system (LNG-IUS). Methods Between April 2009 and February 2011, all women requesting insertion of an intrauterine contraceptive for family planning or noncontraceptive indications were enrolled. One hundred and eight Cu-IUDs and 42 LNG-IUSs were placed. Cervical cytological and vaginal microbiological findings before insertion and after 12 months were recorded. Results With regard to cervical cytology, nonspecific inflammatory changes became more frequent (but not significantly so; p = 0.062) after one year of use of a Cu-IUD, whereas their prevalence remained unchanged among women fitted with a LNG-IUS. Colonisation by Candida spp. and mycoplasma infections were diagnosed significantly more often after one year of use of the Cu-IUD than at baseline. During the study period, women wearing a Cu-IUD complained significantly more frequently of vaginal discharge, pelvic pain, and increased menstrual flow. Conclusion Use of a Cu-IUD – but not that of a LNG-IUS – was associated with an alteration of the vaginal flora and showed a trend towards a higher frequency of nonspecific inflammatory changes affecting cervical cytology.

Do the first, second and third trimester maternal serum hepcidin concentrations clarify obstetric complications?

Abstract Objective: To evaluate whether first, second, and third-trimester maternal serum hepcidin levels are different in pregnancies with and without adverse pregnancy outcomes (APO). Methods: A 165 nullipar pregnant women were included in this prospective cohort study. Serum hepcidin, ferritin, IL-6, C-reactive protein (CRP) and Hb values were measured at 11–14, 24–28, and 30–34 weeks of gestation. The relation between these parameters and APO and neonatal outcomes were investigated. Preterm delivery, intrauterine growth restriction, pre-eclampsia, gestational hypertension and placental abruption were determined as adverse pregnancy outcomes. Results: The risk of APO was three times higher in women with high IL-6 levels in the second trimester. High hepcidin levels in the second trimester were associated with a 1.6 times increased risk of APO. Newborns of women with high IL-6 levels in the third trimester had a 1.6-fold increased risk of neonatal complications. High ferritin levels in the third trimester were associated with minimally increased risk of neonatal complications. Conclusions: Mean serum hepcidin levels were similar in all pregnant women, however, elevated second trimester serum hepcidin and IL-6 levels were associated with a higher risk of APO and high third trimester hepcidin, ferritin and IL-6 levels were associated with higher risk of neonatal complications.

Effect of bupivacaine‑soaked spongostan in cesarean section wound on postoperative maternal health

PurposeTo investigate the efficacy of bupivacaine-soaked spongostan in cesarean section wound for postoperative anxiety level, satisfaction and early postpartum depression rate.MethodsA total of 121 women, American Society of Anesthesiologists physical status I–II, scheduled to undergo general anesthesia and elective cesarean section were recruited and randomized into a study group (nxa0=xa061) or a control group (nxa0=xa060). In the spongostan group, bupivacaine-soaked spongostan was placed in the cesarean section wound. The control group did not receive spongostan, but only general postoperative care. Maternal health was assessed using a visual analog scale for satisfaction, a visual analog scale for anxiety and the Edinburgh Postpartum Depression Scale for postpartum depression. Also, first breast-feeding time, first mobilization time and opioid consumption were recorded and compared.ResultsThe anxiety level of the spongostan group was lower than that of the control group and the difference was statistically significant at all time intervals (1, 6, 12, 18, 24, 30, 36 and 48xa0h, pxa0<xa00.001, respectively). Postpartum depression rate again was significantly lower in the spongostan group both on postoperative day 2 and day 9 (pxa0≤xa00.01). All satisfaction scores were significantly higher in the spongostan group than in the control group (pxa0<xa00.001). Additionally, first breast-feeding and first mobilization times were significantly shorter and opioid consumption was lower in the spongostan group (pxa0<xa00.001).ConclusionPlacement of bupivacaine-soaked spongostan into the cesarean section wound resulted in decreased postoperative anxiety level and postpartum depression rate and increased satisfaction.