Daughters Of Women Research Articles

The Impact of Gestational Diabetes Mellitus on Minipuberty in Girls.

Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty.

8102 Hyperandrogenism and its Influence on Emotional and Social Development in Adolescent Daughters of Women with Polycystic Ovary Syndrome

Abstract Disclosure: J.P. del Rio: None. R. Gonzalo: None. M. Maliqueo: None. B. Echiburu: None. A. Ladron de Guevara: None. P. Gaspar: None. M. Alejandro: None. N.R. Crisosto: None. Introduction: Polycystic Ovarian Syndrome (PCOS) is the most prevalent endocrine disorder in adolescents. PCOS is characterized by hyperandrogenism, which can modulate brain maturation, especially in highly neuronal plasticity periods, such as intra-uterine life and adolescence. Daughters of women with PCOS (dPCOS) will probably be exposed to hyperandrogenism during these two periods. However, the effects of hyperandrogenism on psychosocial development have not yet been fully characterized. Objectives: To characterize the consequences of hyperandrogenism in the emotional status and social cognition (SC) on dPCOS. Methods/Design: Analytical cross-sectional study. dPCOS and controls between 12 to 25 years old were recruited. Participants underwent a complete clinical evaluation, serum hormone determinations (including total testosterone, SHBG, androstenedione, 17-OH-progesterone, and OGTT-I with 4 collections (0’-30’-90’-120´)) and ovarian ultrasound characterization. Emotional status and SC were estimated by measurements of affects (PANAS), strength and difficulties (SDQ), self-reported empathy (EQ/SQ and AQ), and gaze patterns measurement via Eye-Tracking (while completing an emotional recognition task). Results: 33 participants were recruited, 15 cases and 18 controls. Median age was 17 and 18 years, respectively. The dPCOS presented a larger anogenital distance (cm) (9.7 vs 7.8; p=0.014), Ferryman-Gallwey score mean (13.0 vs 2.0; p=<0.001) and free androgen index value (7.5 vs 4.1; p=0.004), suggesting hyperandrogenism exposure during intrauterine and adolescence periods. Regarding emotional status and SC, dPCOS exhibited a predominantly negative affective status (PANAS 8.0 vs 2.0, p=0.049) and a higher score in socio-emotional problems (SDQ 2,5 vs 1,5; p=0,047). The eye-tracking registration showed that dPCOS presented a longer time to first fixation in areas of interest (s) (0,35 vs 0,28; p=0,037), which was associated with a worse endpoint in emotional recognition (aR2=-0,920; f=19,48; Pr >|t|=<0,049). Furthermore, the 2D:4D ratio (intrauterine marker of androgen exposure) and insulin levels at 60’ were correlated with a predominance of negative affects (rho=0,51; p=0,019 and rho= -0,48; p=0,035), and 2D:4D ratio was also correlated with less prosocial behaviors (coef=-2,39; P>|t|=0,049). Conclusions: Clinical and hormonal markers suggest that dPCOS are exposed to hyperandrogenism during the most critical neuroplasticity periods. This exposure is associated with a predominance of negative affects, more social-emotional difficulties and worse performance on emotional recognition and prosocial behavior. Considering PCOS patient’s elevated psychiatric comorbidity, early mental health intervention becomes crucial, underscoring the necessity for in-depth study on hyperandrogenism's impacts on psychosocial development. Presentation: 6/3/2024

8102 Hyperandrogenism and its Influence on Emotional and Social Development in Adolescent Daughters of Women with Polycystic Ovary Syndrome

Abstract Disclosure: J.P. del Rio: None. R. Gonzalo: None. M. Maliqueo: None. B. Echiburu: None. A. Ladron de Guevara: None. P. Gaspar: None. M. Alejandro: None. N.R. Crisosto: None. Introduction: Polycystic Ovarian Syndrome (PCOS) is the most prevalent endocrine disorder in adolescents. PCOS is characterized by hyperandrogenism, which can modulate brain maturation, especially in highly neuronal plasticity periods, such as intra-uterine life and adolescence. Daughters of women with PCOS (dPCOS) will probably be exposed to hyperandrogenism during these two periods. However, the effects of hyperandrogenism on psychosocial development have not yet been fully characterized. Objectives: To characterize the consequences of hyperandrogenism in the emotional status and social cognition (SC) on dPCOS. Methods/Design: Analytical cross-sectional study. dPCOS and controls between 12 to 25 years old were recruited. Participants underwent a complete clinical evaluation, serum hormone determinations (including total testosterone, SHBG, androstenedione, 17-OH-progesterone, and OGTT-I with 4 collections (0’-30’-90’-120´)) and ovarian ultrasound characterization. Emotional status and SC were estimated by measurements of affects (PANAS), strength and difficulties (SDQ), self-reported empathy (EQ/SQ and AQ), and gaze patterns measurement via Eye-Tracking (while completing an emotional recognition task). Results: 33 participants were recruited, 15 cases and 18 controls. Median age was 17 and 18 years, respectively. The dPCOS presented a larger anogenital distance (cm) (9.7 vs 7.8; p=0.014), Ferryman-Gallwey score mean (13.0 vs 2.0; p=<0.001) and free androgen index value (7.5 vs 4.1; p=0.004), suggesting hyperandrogenism exposure during intrauterine and adolescence periods. Regarding emotional status and SC, dPCOS exhibited a predominantly negative affective status (PANAS 8.0 vs 2.0, p=0.049) and a higher score in socio-emotional problems (SDQ 2,5 vs 1,5; p=0,047). The eye-tracking registration showed that dPCOS presented a longer time to first fixation in areas of interest (s) (0,35 vs 0,28; p=0,037), which was associated with a worse endpoint in emotional recognition (aR2=-0,920; f=19,48; Pr >|t|=<0,049). Furthermore, the 2D:4D ratio (intrauterine marker of androgen exposure) and insulin levels at 60’ were correlated with a predominance of negative affects (rho=0,51; p=0,019 and rho= -0,48; p=0,035), and 2D:4D ratio was also correlated with less prosocial behaviors (coef=-2,39; P>|t|=0,049). Conclusions: Clinical and hormonal markers suggest that dPCOS are exposed to hyperandrogenism during the most critical neuroplasticity periods. This exposure is associated with a predominance of negative affects, more social-emotional difficulties and worse performance on emotional recognition and prosocial behavior. Considering PCOS patient’s elevated psychiatric comorbidity, early mental health intervention becomes crucial, underscoring the necessity for in-depth study on hyperandrogenism's impacts on psychosocial development. Presentation: 6/3/2024

Minipuberty in Daughters of Women with Hypothyroidism during Pregnancy.

Minipuberty is a term describing transient postnatal activation of the hypothalamic-pituitary-gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

P-593 developmental programming by maternal androgen excess is mediated by androgen receptor pathways

Abstract Study question How does maternal hyperandrogenism featured PCOS-pregnancy affects the placental and embryo development and further contributes to the development of PCOS-like phenotypes in adult offsping? Summary answer Maternal hyperandrogenism compromises PCOS-pregnancy and embryo development due to placenta dysfunction, leading to the subsequent development of anxiety-like behavior and/or impaired metabolism in adult offspring What is known already Women with PCOS suffer an increased risk of having miscarriage, preterm delivery, and perinatal mortality. The hostile in utero environment because of maternal hyperandrogenism likely play a detrimental role in embryo development as well as the disease susceptibility later in life. As according to previous findings, daughters of women with PCOS have 5 fold increased risk of getting PCOS diagnosis, while sons of women with PCOS suffer from metabolic diseases. Study design, size, duration We used a PCOS-like mouse model induced by continuous exposure to dihydrotestosterone (DHT) from prepuberty, which developed obesity, anovulation, and abnormal ovarian morphology to study the effects of maternal hyperandrogenism during pregnancy. In comparison, we also simultaneously treated PCOS-like females with flutamide, an androgen-receptor blocker. We examined embryos at E10.5 and E13.5 focusing on placentas in relation to embryo development. Their male and female offspring is also phenotyped until 6 months of age. Participants/materials, setting, methods To explore molecular mechanisms contributing to the developmental defects, whole genome bisulfite and bulk RNA sequencing of placenta were performed. Human Trophoblast organoid culture under different conditions was applied to further evaluate the detrimental effects of maternal hyperandrogetism in placental development. With the help of trophoblast organoid culture system, possible treatment options are also going to be explored. Main results and the role of chance We found a lower pregnancy rate and impaired placentas together with defective embryonic development, which was partially prevented when co-treated with the androgen receptor blocker, flutamide. RNA sequencing of the placenta revealed that DHT severely interferes with placental and fetal development, which are prevented by the treatment with flutamide. In addition, the placenta from DHT-exposed dams showed impaired differentiation capacity of cell types located in the labyrinth. The hyperandrogenic maternal environment led to the development of anxiety-like behavior and impaired metabolism in adult male offspring and partial disturbance in the metabolism of female offspring later in life. The effect of hyperandrogenism on trophoblast differentiation and metabolic capacity is still under investigation. Limitations, reasons for caution Although androgen receptor pathway was found to be responsible for placental and fetal abnormalities and the development of adult phenotypes, and the treatment with flutamide prevented most of the unfavorable effects, the use of flutamide in clinic is tightly regulated and not suggested for women with PCOS. Wider implications of the findings Maternal hyperandrogenism greatly compromises PCOS-pregnancy and embryo development due to placenta dysfunction, leading to the subsequent development of unfavorable phenotypes in adult offspring. Such effects are mainly mediated by the androgen receptor pathway as the administration of flutamide partially prevents the compromised placenta and fetal development. Trial registration number not applicable

Spatially Varying Intergenerational Changes in the Prevalence of Female Genital Mutilation/Cutting in Nigeria: Lessons Learnt from a Recent Household Survey

Considering the concerted investments in anti-female genital mutilation/cutting (FGM/C) campaigns championed by the Nigerian government and non-governmental organizations, research findings suggest that reduction in intergenerational (mother-to-daughter) prevalence of FGM/C in Nigeria has been very slow. What can we learn from the 2018 Nigerian Demographic and Health Survey (2018 NDHS) about the roles of the key drivers of mother-to-daughter FGM/C prevalence in Nigeria? Here, drawing upon the 2018 NDHS dataset, we provided a context-specific study on the geographical patterns and the enabling factors of intergenerational trends in FGM/C among Nigerian women aged 15 – 49 years and their daughters aged 0 – 14 years. Using Bayesian semi-parametric geo-additive regression model, we simultaneously controlled for the effects of individual-level, community-level and unobserved geographical factors. We learnt that although there has been an overall decline in mother-to-daughter prevalence of FGM/C, the practice persists in Nigeria largely due to geographical location and social norm related factors – risk was high among daughters of circumcised women and daughters of women who supported the continuation of FGM/C. We identified Kano, Kaduna, Imo and Bauchi states as the hotspots and there was an increased risk of FGM/C among daughters of women who lived in the neigbouring states of Jigawa and Yobe. Daughters of circumcised women were about 2.7 times more likely to be cut. We recommend the development of tailored community-level interventions targeting circumcised women in the hotspot states and their neighbours to ensure a total eradication of female circumcision in Nigeria by the year 2030.

LBMON237 Predictors Of Postmenarchal Progression Of Pcos Phenotypes In At-risk Girls

Abstract Physiologic and genetic analyses implicate hyperandrogenemia (HA) as a core causal pathway in PCOS. Both daughters of women with PCOS (PCOS-d) and overweight/obese girls (OW-g) have HA beginning in childhood suggesting that they are at increased risk for PCOS. Accordingly, we performed a prospective study of girls in the early postmenarchal transition until the diagnosis of PCOS can be established according to clinical guidelines at 2 or more yrs after menarche. | PCOS-d, OW-g and lean control girls (LC), ages 11-16 yrs at baseline, were studied within 0.2-1.2 yrs of menarche and returned after 1-3 years. Two PCOS-d, 2 OW-g, and 4 LC could not be assessed at follow up because they were taking hormonal contraception, which was most often prescribed for irregular menses. Baseline and follow up sample sizes were: PCOS-d 16, 12; OW-g 13, 9; LC 18, 14. A fasting morning blood sample was obtained. | Age was similar but BMI differed by design. The change in BMI from baseline to follow up did not differ between the groups. At baseline, DHEAS levels were increased (P=0. 009) and SHBG levels decreased (P<0. 001) in PCOS-d and OW-g. In contrast, LH levels were higher only in PCOS-d (P=0. 03), whereas insulin levels were increased only in OW-g (P=0. 01). At baseline, the prevalence of HA (T, fT or DHEAS > LC mean + 1 SD) was increased (χ2 P=0. 04) in PCOS-d (69%) compared to OW-g (62%) and LC (28%). The prevalence of ovulatory dysfunction (OD, menses >45 d or <21 d) was also increased (χ2 P=0. 04) in PCOS-d (63%) compared with OW-g (15%) and LC (18%). All PCOS-d and 75% OW-g and LC had persistent HA at follow-up. Thirty-eight percent of PCOS-d had persistent OD, while 1 of 2 LC had persistent OD. Neither OW-g with OD at baseline returned for follow up. Two PCOS-d, 2 OW-g and 1 LC fulfilled PCOS criteria at follow up. One of these PCOS-d also had HA and OD at baseline, one OW-g developed both HA and OD. A model that included BMI, SHBG, fasting insulin and LH levels at baseline predicted PCOS diagnosis after 2-yrs of follow up with a Receiver-Operator-Curve area-under-the-curve of 0.98. | There was an increased prevalence of HA in PCOS-d and OW-g early postmenarche that persisted after 2-yrs postmenarche. PCOS-d also had an increased prevalence of OD early postmenarche, which aligns with their increased LH levels at baseline. These findings suggest neuroendocrine dysfunction in PCOS-d, which appears to improve with pubertal maturation, since in the majority of PCOS-d, OD resolved. In contrast, OW-g were hyperinsulinemic. There were no significant differences in the prevalence of PCOS at follow up, although there may have been bias because of preferential exclusion of girls with OD due to hormonal contraception. A model of biomarkers in early postmenarchal girls, that included both reproductive and metabolic parameters, was highly predictive of PCOS diagnosis at follow up. Girls with HA should still be considered at risk for PCOS and require ongoing monitoring. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Effects of Elevated Maternal Adiposity on Offspring Reproductive Health: A Perspective From Epidemiologic Studies.

One in seven couples in developed countries suffers from infertility. Maternal overweight or obesity have detrimental and lasting effects on offspring cardiometabolic health, and although substantially more data are needed, hormonal imbalances in utero resulting from excessive maternal adiposity could also disrupt reproductive programming and affect the future reproductive health of offspring. Therefore, this mini-review evaluates the human epidemiologic evidence that maternal overweight/obesity could be associated with poor reproductive health outcomes in offspring. We searched PubMed for relevant studies using terms such as "maternal obesity" and "reproductive development." While the human epidemiologic literature is limited, studies have thus far observed that maternal obesity is associated with disrupted external genital development and several other markers of reproductive health across the lifespan. Specifically, maternal obesity is associated with higher risks of hypospadias and cryptorchidism in males and disrupted anogenital distance both in males and females. Maternal obesity has also been linked to earlier age at menarche in daughters, and precocious puberty in both sons and daughters. Finally, daughters of women with overweight or obesity have higher risks of developing polycystic ovarian syndrome, which has implications for fertility. This body of research suggests that in utero exposure to maternal obesity could disrupt reproductive system development, but substantially more evidence is needed, as almost no human epidemiologic studies have evaluated the long-term consequences of maternal obesity with regard to offspring fertility/fecundity.

The Book Woman's Daughter by Kim Michele Richardson

Reviewed by: The Book Woman's Daughter by Kim Michele Richardson Donna M. Crow (bio) Kim Michele Richardson. The Book Woman's Daughter. Naperville, Ill.: Mercer University Press, 2022. 352 pages. Hardover. $26.99. For readers who loved Kim Michelle Richardson's The Book Woman of Troublesome Creek, this sequel offers another visit to the hills of Eastern Kentucky, only one generation after the WPA implemented the Packhorse Librarian Project. Yet, The Book Woman's Daughter stands alone as a simple, sweet story layered with the dark, complicated issues which still haunt Appalachia today. One hundred years after the first large public library was erected in Boston, while library buildings were popping up all over the country, in 1952 Appalachia, books were still carried on horseback across narrow footpaths into hollers, up hillsides, and along high ridges. The lack of infrastructure in difficult terrain has kept the descendants of early settlers regionally isolated, causing Appalachia to be one of the last places in America to obtain modern living standards. In this fictionalized but true Appalachian tale, many struggle for literacy and yearn for news of the outside world, while others fearfully hang on to the only lives they've known. These livelihoods are filled with family values, hardscrabble survival, loyal friendships, and desire for education, yet rife with the racism, miscegenation laws, and misogyny that plague the systems of patriarchy and white supremacy. [End Page 112] In The Book Woman's Daughter, Richardson balances these juxtaposed ideals by challenging stereotypes, utilizing strong female characters, and forging unlikely friendships. The narrator's infectious love of books, the expansion of literacy, the empowerment of women, and the desire for equality, freedom and justice are the emergent themes. "'Freedom. The word rattled my thoughts. I was relieved there might be a chance of getting it without marrying,"' says our protagonist. "'I was grateful…, but even more appreciative for the librarian work. A job and money-and the books-meant I could at least survive, and do it on my own'". Her literary identity provides Honey with a freedom she struggles to find in her everyday life. The novel is set in the early fifties and told through the eyes of Honey Lovett, the child Cussy Mary Lovett adopted in the first novel. Readers will remember that Cussy built her reputation among hill-folk as a "bookwoman" who served as part of the Packhorse Librarian Project and provided valuable access to books for her people. Both women carry a genetic trait that causes the blood disorder methemoglobinemia, which tints the skin blue. Both women also have an insatiable appetite for "book-learning" and prove that books are transformative. Months after reading The Book Woman's Daughter, like The Book Woman of Troublesome Creek, what sticks are the characters. These characters include the mountain bootlegger who is a compassionate advocate for women's rights and the female social worker who seems hell-bent on sending a minor to jail mainly because of her skin color. The opening scene sets the stage of trouble for Honey as her parents are whisked away to jail for the legal infraction of having a mixed-race marriage. Being underage and of blue tint herself puts Honey at risk for incarceration as well, so [End Page 113] she must stay hidden while she struggles for emancipation. As she embarks on her freedom journey, she comes across a young woman who is just arriving for her new job as the first woman fire-tower watcher in the region. "Being different here in white or black Kentucky puts you on the lowest rung," Honey explains to her new friend. "'[I]t's not against the law to be a minor,'" her friend replies. "'Shouldn't be against the law to love someone either' says Honey, 'But it sure ought to be against the law for men to decide who you can and can't love'". The two young women become a formidable force against discrimination over the course of the novel. To some, the book may come across as not being "male-friendly," but upon deeper analysis, there are as many female oppressors as there are male and as many male advocates...

Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: implications for breast cancer risk.

Earlier onset of breast development (thelarche) is associated with increased breast cancer risk. Identifying modifiable factors associated with earlier thelarche may provide an opportunity for breast cancer risk reduction starting early in life, which could especially benefit girls with a greater absolute risk of breast cancer due to family history. We assessed associations of maternal pre-pregnancy body mass index (BMI), physical activity during pregnancy, gestational weight gain and daughters' weight and length at birth with age at thelarche using longitudinal Weibull models in 1031 girls in the Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study-a prospective cohort of girls, half of whom have a breast cancer family history (BCFH). Girls whose mothers had a pre-pregnancy BMI of ≥25 and gained ≥30lbs were 57% more likely to experience earlier thelarche than girls whose mothers had a pre-pregnancy BMI of <25 and gained <30 lbs [hazard ratio (HR) = 1.57, 95% CI: 1.16, 2.12]. This association was not mediated by childhood BMI and was similar in girls with and without a BCFH (BCFH: HR = 1.41, 95% CI: 0.87, 2.27; No BCFH: HR = 1.62, 95% CI: 1.10, 2.40). Daughters of women who reported no recreational physical activity during pregnancy were more likely to experience earlier thelarche compared with daughters of physically active women. Birthweight and birth length were not associated with thelarche. Earlier thelarche, a breast cancer risk factor, was associated with three potentially modifiable maternal risk factors-pre-pregnancy BMI, gestational weight gain and physical inactivity-in a cohort of girls enriched for BCFH.

Predictors of Female Genital Mutilation or Cutting Among Daughters of Women in Guinea, West Africa

Background and Objective: In some African countries like Guinea, female genital mutilation/cutting (FGM/C) has been considered as an essential social norm in ensuring girls’ and women’s virginity by reducing their sexual desires. This study aimed at examining the factors associated with FGM/C among daughters of women aged 15-49 in Guinea. Methods: Using the 2018 Guinea Demographic and Health Survey, we analyzed data on 10,721 women of reproductive age (15-49 years) who had at least one daughter. A two-level multi-level logistic regression analysis was fitted and the random and fixed effects together with their corresponding 95% credible intervals (95% CrIs) were presented. Results: Women of all age categories had higher odds of having circumcised daughters with the substantially highest odds among those aged 35-39 (aOR=26.10, CrI=11.22-53.94) compared to those aged 15-19. “FGM/C was higher among daughters of circumcised mothers (aOR=5.50, CrI=3.11-9.72), compared to those who were not circumcise. Compared to Muslims, women who were either animists or had no religion were more likely to circumcise their daughters (aOR=2.13, CrI=1.12-4.05). Conversely, women with secondary/higher education, whose partners had secondary/higher education, Christians, women of richest wealth index and those who lived in the Faranah and N’zerekore regions were less likely to circumcise their daughters. Conclusion and Implications for Translation: The current study revealed that individual and contextual factors are associated with FGM/C among daughters of women aged 15-49 in Guinea. The findings imply that eliminating FGM/C in Guinea requires multifaceted interventions such as advocacy and educational strategies like focus group discussions, peer teaching, mentor-mentee programs in regions noted with the FGM/C practice. This will help achieve the Sustainable Development Goal 5.3 which focuses on eliminating all harmful practices, such as child, early and forced marriage and female genital mutilation by 2030. Copyright © 2021 Ahinkorah. et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Pain catastrophizing in daughters of women with fibromyalgia: a case-control study

Fibromyalgia is a syndrome characterized by chronic pain related to the musculoskeletal system. Patients feel incapable and show catastrophic thoughts (exaggeration of the sensations) related to painful events. This study aimed to compare catastrophic thoughts of pain between daughters of women with fibromyalgia and daughters of women without fibromyalgia, no daughter having the syndrome. It was a case-control study in which 76 women were included: 38 daughters of women diagnosed with fibromyalgia (case group), and 38 daughters of women without fibromyalgia (control group). The Brazilian versions of the Profile of Chronic Pain: Screen, the Pittsburgh Sleep Quality Index, the Pain Catastrophizing Scale, Resilience Scale, Beck Depression Inventory-II, and the State-Trait Anxiety Inventory were used. Data were tabulated and analyzed using SPSS 20.0. Continuous variables were compared between the groups using the Mann-Whitney U test or Student’s t-test for independent samples. A significant difference was considered at p < 0.05. Regarding catastrophism, the case group had higher total catastrophism compared to the control group (p = 0.025). Daughters of patients with fibromyalgia showed higher rumination and magnification levels related to pain (p = 0.028 and p = 0.007, respectively) but did not show hopelessness. This study concludes that daughters of women with fibromyalgia are more likely to have symptoms of fibromyalgia due to their visualization of the syndrome. This indicates that emotional aspects may induce changes, and additional research on an individual basis is necessary.

Age at menarche in Seveso daughters exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In 2014, nearly 40 years after the explosion, we enrolled postexplosion offspring, 2 to 39 years of age, in the Seveso Second Generation Study. Age at onset of menarche (years) was collected for 316 daughters by maternal report or self-report at interview. In utero TCDD exposure was defined by maternal TCDD serum concentrations extrapolated to the pregnancy. At interview, 287 daughters were postmenarche and reported age at menarche averaged 12.1 years (±1.3 years). Overall, we found no change in risk of menarche onset with a 10-fold increase in in utero TCDD exposure (hazard ratio [HR] = 0.86; 95% confidence interval [CI] = 0.71, 1.04). When we considered maternal menarche status in 1976 as a potentially sensitive developmental exposure window, in utero TCDD (log10) was associated with later age at menarche among daughters whose mothers were premenarche (HR = 0.71; 95% CI = 0.52, 0.97) but not postmenarche (HR = 0.89; 95% CI = 0.71, 1.12) at the time of the explosion (P int = 0.24). These results suggest that in utero TCDD exposure may alter pubertal timing among daughters of women who were prepubescent at the time of the Seveso accident.

Prenatal Androgenization Alters the Development of GnRH Neuron and Preoptic Area RNA Transcripts in Female Mice.

Polycystic ovary syndrome (PCOS) is the most common form of infertility in women. The causes of PCOS are not yet understood and both genetics and early-life exposure have been considered as candidates. With regard to the latter, circulating androgens are elevated in mid-late gestation in women with PCOS, potentially exposing offspring to elevated androgens in utero; daughters of women with PCOS are at increased risk for developing this disorder. Consistent with these clinical observations, prenatal androgenization (PNA) of several species recapitulates many phenotypes observed in PCOS. There is increasing evidence that symptoms associated with PCOS, including elevated luteinizing hormone (LH) (and presumably gonadotropin-releasing hormone [GnRH]) pulse frequency emerge during the pubertal transition. We utilized translating ribosome affinity purification coupled with ribonucleic acid (RNA) sequencing to examine GnRH neuron messenger RNAs from prepubertal (3 weeks) and adult female control and PNA mice. Prominent in GnRH neurons were transcripts associated with protein synthesis and cellular energetics, in particular oxidative phosphorylation. The GnRH neuron transcript profile was affected more by the transition from prepuberty to adulthood than by PNA treatment; however, PNA did change the developmental trajectory of GnRH neurons. This included families of transcripts related to both protein synthesis and oxidative phosphorylation, which were more prevalent in adults than in prepubertal mice but were blunted in PNA adults. These findings suggest that prenatal androgen exposure can program alterations in the translatome of GnRH neurons, providing a mechanism independent of changes in the genetic code for altered expression.

Abstract A17: In utero DDT exposure and breast density in early menopause by maternal history of breast cancer

Abstract Studies examining intrauterine environmental exposures and breast cancer risk are challenged by the long induction period between exposure and breast cancer development. One strategy to address this challenge is to examine the relationship between exposures and intermediate markers of breast cancer risk. Mammographic breast density (MBD) is considered an intermediate marker for breast cancer—having mostly dense breasts is associated with nearly a 4-fold increase in breast cancer as compared with having mostly fatty breasts. Here we examined the relation between intrauterine dichlorodiphenyltrichloroethane (DDT) exposure (o,p’-DDT, p,p’-DDT, and p,p’-DDE) to MBD in midlife. We focused our analyses on o,p’-DDT exposure when mutually adjusted for p,p’-DDE given our previous report of a positive association between intrauterine o,p’-DDT exposure and daughters’ breast cancer (BC) risk. We estimated associations of early postpartum serum DDTs with MBD in 224 daughters of women in the Child Health and Development Studies pregnancy cohort whose mothers did not develop BC (MBCa-negative) and 156 daughters whose mothers did develop BC (MBCa-positive). In MBCa-positive daughters, highest relative to lowest quartile of o,p’-DDT exposure was associated with a 17-unit higher dense area (95% CI= 2.6-31.2; Ptrend=0.01); associations persisted after adjusting for p,p’-DDT. MBD, an important intermediate marker of BC risk, may be affected by intrauterine DDT exposures; MBCa status may modify the association. Citation Format: Jasmine A. McDonald, Piera M. Cirillo, Parisa Tehranifar, Nickilou Y. Krigbaum, Natalie Engman, Barbara A. Cohn, Mary Beth Terry. In utero DDT exposure and breast density in early menopause by maternal history of breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A17.

DNA methylation in promoter regions of genes involved in the reproductive and metabolic function of children born to women with PCOS

ABSTRACT Clinical and experimental evidences indicate that epigenetic modifications induced by the prenatal environment are related to metabolic and reproductive derangements in polycystic ovary syndrome (PCOS). Alterations in the leptin and adiponectin systems, androgen signalling and antimüllerian hormone (AMH) levels have been observed in PCOS women and in their offspring. Using a targeted Next-Generation Sequencing (NGS), we studied DNA methylation in promoter regions of the leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), adiponectin receptor 1 and 2 (ADIPOR1 and ADIPOR2), AMH and androgen receptor (AR) genes in 24 sons and daughters of women with PCOS (12 treated with metformin during pregnancy) and 24 children born to non-PCOS women during early infancy (2–3 months of age). Genomic DNA was extracted from whole blood, bisulphite converted and sequenced by NGS. Girls showed differences between groups in 1 CpG site of LEPR, 2 of LEP, 1 of ADIPOR2 and 2 of AR. Boys showed differences in 5 CpG sites of LEP, 3 of AMH and 9 of AR. Maternal metformin treatment prevented some of these changes in LEP, ADIPOR2 and partially in AR in girls, and in LEP and AMH in boys. Maternal BMI at early pregnancy was inversely correlated with the methylation levels of the ChrX-67544981 site in the whole group of girls (r = −0.530, p = 0.008) and with the global Z-score in all boys (r = −0.539, p = 0.007). These data indicate that the intrauterine PCOS environment predisposes the offspring to acquire certain sex-dependent DNA methylation patterns in the promoter regions of metabolic and reproductive genes.

Effect of excessive gestational weight on daughters\u2019 breast density at the end of puberty onset

The effect of excessive gestational weight gain (EGWG) is related to adverse health outcomes in the offspring; however, its effect on the daughters’ breast density is unclear. We aimed to assess the association between EGWG and daughters’ breast composition (% of fibroglandular volume (%FGV) and absolute fibroglandular volume (AFGV)) at Tanner stage 4 (Tanner B4)). We included 341 girls and their mothers from an ongoing cohort of low-income Chilean girls born from 2002–2003. Maternal gestational weight gain was self-reported in 2007, and breast density by digital mammography was measured in 2010. Weight, height and breast composition by dual X-ray absorptiometry (DXA) were measured in daughters at Tanner B4. Logistic regression models were run to assess the association between EGWG and the 80th percentile of %FGV and AFGV. Mean gestational weight gain was 13.7 kg (SD = 6.9 kg). Women with pregestational overweight or obesity exceeded the recommended gestational weight gain (58.8% vs. 31.8%, respectively). Daughters of women who had EGWG had higher levels of AFGV (OR: 2.02; 95%CI 1.16–3.53) at Tanner B4, which could be explained by metabolic and hormonal exposure in utero. However, we did not observe an association with %FGV.

Genital tract and reproductive characteristics in daughters of women and men prenatally exposed to diethylstilbestrol (DES)

Prenatal exposure of women to diethylstilbestrol (DES) has been associated with reproductive tract anomalies, menstrual irregularity, infertility and pregnancy complications. In prenatally exposed men, adverse effects included genital anomalies and possible risk of infertility. In children of prenatally exposed women, i.e the third generation, an increased incidence of genital defects was observed in sons (hypospadias), but not in daughters. In daughters of prenatally exposed men, the incidence of genital anomalies was in the normal range. Experimental studies in mice evidenced an increased incidence of reproductive tract anomalies in the female descendants of females and males prenatally exposed to DES, indicative of transgenerational transmission of DES defects. The aim of this study is to assess genital tract defects, fertility and pregnancy outcome, in daughters of women and men prenatally exposed to DES. In a retrospective observational analysis, 759 daughters of prenatally exposed women and men reported their genital and reproductive characteristics that were compared with those of: 1) general population in France; 2) two cohorts of daughters of exposed women reported in previous publications; 3) women prenatally exposed to DES. An increased incidence of uterine defects was observed, with both doubling of uterus and bicornuate and aplastic uterus which constitutes the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS). No specific anomalies described in prenatally exposed women such as T-shape or hypoplastic uterus were reported. Infertility appeared to be in the normal range. Pregnancy outcomes of our 121 pregnancies of women born to DES exposed mothers and two other published cohorts presented inconsistent results for ectopic pregnancy, miscarriage and preterm delivery. Early and late miscarriages were higher than expected in general population in our cohort but not in the two others. These results must be considered as preliminary, due to the small numbers of patients, limited follow-up duration after birth due to young age of the studied population, and observational methods. An important point is that the high risk of reproductive dysfunction of women prenatally exposed to DES was not observed in their daughters. There is a signal on the high incidence of uterine defects, especially aplastic uterus, and its possible link with DES exposure through epigenetic effects is discussed in our findings. Inconsistent findings regarding pregnancy outcomes in the third generation are worthy of further examination.

Foreigners

Foreigners Fabienne Josaphat (bio) Lucien stared at the Thanksgiving display before him. A whole turkey, roasted and stuffed with a crumbly paste, rested belly-up on a bed of parsley. Its legs were twined together in a barbaric manner, as if Virginie, his ex-wife, had mercilessly arrested and restrained the animal before plucking it and shoving it into the oven. Ida, his daughter, tipped over a can onto a plate, releasing a crimson jelly she then sliced into uneven parts. "C'est quoi, ça?" Lucien's mouth twitched and he asked again, in English, testing his limited vocabulary. "What is this?" Ida moved her red lips. "Cranberry. Une sauce. For the turkey." "A sauce?" Lucien eyed his daughter, who had moved on to other things, roasted green beans and a gratin of macaroni. "Paul! Michael! Let's eat!" she called to her brother and husband. As they came into the dining room, Lucien tried to catch phrases, pieces of English he could understand, something about American football, a game he didn't grasp. In Haiti at this time, he would have been lying on his patio with a Plagatox mosquito coil and a fan, reading a book to thwart the loneliness of his single life. But he was in America visiting his children and his ex-wife, his missing body parts, he called them, driftwood swimming away from their native land. He found Thanksgiving both absurd and bizarre. Absurd because he could not fathom a celebration of food and gratitude for a land taken from Natives, and bizarre because he couldn't wrap his brain around Haitians joining in this ritual. The way Virginie had slaved over this meal, perched over the stove, stirring and sweating all morning, was an outrage. The way they now ogled the roasted bird was unsettling. "How are you doing, Papi?" Michael, his son-in-law, hadn't learned much French, even though he'd been married to Ida for three years. The only Haitian words he smuggled into conversations were "Papi" and "Merci." Lucien had visited them just the other day, in their community where the "townhomes" held hands like monochromatic pencils in their box. He had noticed Post-it Notes stuck to household items, phonetically spelling objects' names in Creole. The one on the water pitcher read "dlo," and the door read "pòt." He'd quizzed Ida about the language she'd chosen to help Michael learn. "Why not French?" "Why not Creole?" Her eyes went fiery at his suggestion. "It's our maternal tongue, not the language of colonization, and it's easier for him to learn." Lucien offered no reply. Ida would never change. Sometimes he was convinced she was some other woman's daughter. Ida's own mother was never this rebellious. Virginie's only act of rebellion had been to buy a plane ticket ten years ago and escape Haiti with the children, leaving him no letter to explain her departure. There had been warning signs, of course, but he was convinced her threats to divorce him and her combative arguments were womanly caprice. Looking at his family now, gathered around [End Page 124] this table like specters, he knew he'd underestimated her. It took ten years of arguing and pleading for a reconciliation. Five years ago, Virginie called Lucien on the phone and told him she wanted an official, documented severance of their love story. He was swatting mosquitoes away on his patio that hot night in Port-au-Prince, his body failing to adjust to the news. Why hadn't he prepared for this? He didn't know. "We don't need to be enemies," Virginie had said to him. "But we weren't meant to be married. You don't know how." She sounded disturbingly calm, her tone dipped in so much goodness he found it repulsive. "You are always welcome to visit us in Miami. You can stay over in the guest room if you need to." Lucien spat on the ground and said nothing. He despised being abandoned and vulnerable. Visit her in Miami? Never. But now here he was, seated at their table, the last ten years of solitude gnawing...