Pregnancy losses in young Australian women : findings from the Australian Longitudinal Study on Women's Health

INTRODUCTION: Little research has examined recognized pregnancy losses in a general population. Data from an Australian cohort study provide an opportunity to quantify this aspect of fecundity at a population level. METHOD: Participants in the Australian Longitudinal Study on Women's Health who were aged 28-33 years in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants were categorized according to the recognized outcome of their pregnancies, including live birth, miscarriage/stillbirth, termination/ectopic, or no pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%) was as common as termination (16%). For women aged 28-33 years who had ever been pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss only (18%); and birth and loss (32%), of which half (16%) were birth and miscarriage. A comparison between first miscarriage and first birth (no miscarriage) showed that most first miscarriages occurred in women aged 18-23 years who also reported a first birth at the same survey (15%). Half (51%) of all first births and first miscarriages in women aged 18-19 ended in miscarriage. Early childbearers (<28 years) often had miscarriages around the same time period as their first live birth, suggesting proactive family formation. Delayed childbearers (32-33 years) had more first births than first miscarriages. CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in the general population because they indicate successful conception and maintenance of pregnancy to varying reproductive endpoints.

History behind the egg: Women's comprehensive histories and IVF outcomes, Australia, 2008-2009 [abstract]

The individual history of infertile women, as well as their age, may influence their response to in vitro fertilisation (IVF) cycles. This study examined the associations between women’s histories and two IVF outcomes: eggs aspirated (EA) and proportion with normal, two-pronuclei (2PN), fertilisation. This is a cross-sectional survey of infertile women (n=141, 27-46 years) from a multi-centre clinical sample. Participants completed a survey of socio-demographic, relationship, lifestyle, reproductive and fertility factors, medical conditions and recurrent symptoms. Among participants with heterosexual partners (n=122), associations between women’s histories and EA or 2PN fertilisation were analysed using linear and logistic modelling, respectively, adjusted for age at EA and accounting for multiple IVF cycles (n=313 cycles). Participants aged 35+ years had reproductive histories of miscarriage only (16.9%), termination only (9.9%) or birth+termination (5.6%) that were 2-, 3- and 4-fold higher, respectively, than those aged <35 years (7.1%, 2.9%, 1.4%). More years of oral contraceptive use were associated with a lower mean EA: never used, 14.6 EA; 0-2 years, 11.7 EA; 3-5 years, 8.6 EA; 6þ years, 8.2 EA (p=.04). Participants with polycystic ovary syndrome had a higher mean EA (11.5) than those without the condition (8.3 EA, p<.01). Participants in trade or service occupations had lower proportions of 2PN fertilisation (51.7%) than participants in other occupations (professional, 58.6%; manual/other, 63.6%, p<.02). Increasing women’s age and prolonged used of oral contraceptives were associated with lower EA from IVF cycles; PCOS was associated with higher EA. Occupational exposures may have a detrimental effect on normal fertilisation rates.

Depression: an emotional obstacle to seeking medical advice for infertility

Objective: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. Design: Longitudinal cohort study.Setting Population based.Patient(s) Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936).Intervention(s) None.Main Outcome Measure(s) Infertility, not seeking medical advice. Result(s): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. Conclusion(s): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility.

History behind the IVF egg: Are women's comprehensive histories associated with the number of eggs collected, or fertilised normally, from repeated IVF cycles? [abstract]

Most studies of in vitro fertilisation (IVF) outcomes use cycle-based data and fail to account for women who use repeated IVF cycles. The objective of this study was to examine the association between the number of eggs collected (EC) and the percentage fertilised normally, and women’s self-reported medical, personal and social histories. This study involved a crosssectional survey of infertile women (aged 27-46 years) recruited from four privately-owned fertility clinics located in major cities of Australia. Regression modeling was used to estimate the mean EC and mean percentage of eggs fertilised normally: adjusted for age at EC. Appropriate statistical methods were used to take account of repeated IVF cycles by the same women. Among 121 participants who returned the survey and completed 286 IVF cycles, the mean age at EC was 35.2 years (SD 4.5). Women’s age at EC was strongly associated with the number of EC: <30 years, 11.7 EC; 30.0-< 35 years, 10.6 EC; 35.0-<40.0 years, 7.3 EC; 40.0+ years, 8.1 EC; p<.0001. Prolonged use of oral contraceptives was associated with lower numbers of EC: never used, 14.6 EC; 0-2 years, 11.7 EC; 3-5 years, 8.5 EC; 6þ years, 8.2 EC; p=.04. Polycystic ovary syndrome (PCOS) was associated with more EC: have PCOS, 11.5 EC; no, 8.3 EC; p=.01. Occupational exposures may be detrimental to normal fertilisation: professional roles, 58.8%; trade and service roles, 51.8%; manual and other roles, 63.3%; p=.02. In conclusion, women’s age remains the most significant characteristic associated with EC but not the percentage of eggs fertilised normally.

Unintended pregnancies : reducing rates by improving access to contraception

Unintended pregnancies have significant social, health and financial costs. Importantly, there is surprisingly little information available about the prevalence of unintended pregnancy in Australia. We are currently investigating unintended pregnancy and access to contraception among women aged 18–23 years in rural and urban areas of New South Wales. This is the first step toward understanding how access to effective contraception can be improved and could act as a pilot study for a regular survey of fertility.

Birth outcomes after spontaneous or assisted conception among infertile Australian women aged 28 to 36 years: A prospective, population-based study

Objective To examine the extent to which the odds of birth, pregnancy, or adverse birth outcomes are higher among women aged 28 to 36 years who use fertility treatment compared with untreated women. Design Prospective, population-based. Setting Not applicable. Patient(s) Participants in the ALSWH born in 1973 to 1978 who reported on their infertility and use of in vitro fertilization (IVF) or ovulation induction (OI). Intervention(s) Postal survey questionnaires administered as part of ALSWH. Main Outcome Measure(s) Among women treated with IVF or OI and untreated women, the odds of birth outcomes estimated by use of adjusted logistic regression modeling. Result(s) Among 7,280 women, 18.6% (n = 1,376) reported infertility. Half (53.0%) of the treated women gave birth compared with 43.8% of untreated women. Women with prior parity were less likely to use IVF compared with nulliparous women. Women using IVF or OI, respectively, were more likely to have given birth after treatment or be pregnant compared with untreated women. Women using IVF or OI were as likely to have ectopic pregnancies, stillbirths, or premature or low birthweight babies as untreated women. Conclusion(s) More than 40% of women aged 28–36 years reporting a history of infertility can achieve births without using treatment, indicating they are subfertile rather than infertile.

Miscarriage, preterm delivery, and stillbirth: Large variations in rates within a cohort of Australian women

Objectives We aimed to use simple clinical questions to group women and provide their specific rates of miscarriage, preterm delivery, and stillbirth for reference. Further, our purpose was to describe who has experienced particularly low or high rates of each event. Methods Data were collected as part of the Australian Longitudinal Study on Women's Health, a national prospective cohort. Reproductive histories were obtained from 5806 women aged 31–36 years in 2009, who had self-reported an outcome for one or more pregnancy. Age at first birth, number of live births, smoking status, fertility problems, use of in vitro fertilisation (IVF), education and physical activity were the variables that best separated women into groups for calculating the rates of miscarriage, preterm delivery, and stillbirth. Results Women reported 10,247 live births, 2544 miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who had high rates of miscarriage typically had fewer live births, were more likely to smoke and were more likely to have tried unsuccessfully to conceive for ≥12 months. The highest proportion of live preterm delivery (32.2%) occurred in women who had one live birth, had tried unsuccessfully to conceive for ≥12 months, had used IVF, and had 12 years education or equivalent. Women aged 14–19.99 years at their first birth and reported low physical activity had 38.9 stillbirths per 1000 live births, compared to the lowest rate at 5.5 per 1000 live births. Conclusion Different groups of women experience vastly different rates of each adverse pregnancy event. We have used simple questions and established reference data that will stratify women into low- and high-rate groups, which may be useful in counselling those who have experienced miscarriage, preterm delivery, or stillbirth, plus women with fertility intent.

Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma : a meta-analysis and systematic review of the literature

Objectives: To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or early endometrial adenocarcinoma (EC). Methods: A systematic search identified 3245 potentially relevant citations. Studies containing less than ten eligible CAH or EC patients in either oral or intrauterine treatment arm were excluded. Only information from patients receiving six or more months of treatment and not receiving other treatments was included. Weighted proportions of patients achieving pCR were calculated using R software. Results: Twelve studies met the selection criteria. Eleven studies reported treatment of patients with oral (219 patients, 117 with CAH, 102 with grade 1 Stage I EC) and one reported treatment of patients with intrauterine progestin (11 patients with grade 1 Stage IEC). Overall, 74% (95% confidence interval [CI] 65-81%) of patients with CAH and 72% (95% CI 62-80%) of patients with grade 1 Stage I EC achieved a pCR to oral progestin. Disease progression while on oral treatment was reported for 6/219 (2.7%), and relapse after initial complete response for 32/159 (20.1%) patients. The weighted mean pCR rate of patients with grade 1 Stage I EC treated with intrauterine progestin from one prospective pilot study and an unpublished retrospective case series from the Queensland Centre of Gynaecologic Oncology (QCGC) was 68% (95% CI 45- 86%). Conclusions: There is a lack of high quality evidence for the efficacy of progestin in CAH or EC. The available evidence however suggests that treatment with oral or intrauterine progestin is similarly effective. The risk of progression during treatment is small but longer follow-up is required. Evidence from prospective controlled clinical trials is warranted to establish how the efficacy of progestin for the treatment of CAH and EC can be improved further.

Recovery and reuse of ammonium from wastewater treatment plants : an application for agriculture

In wastewater treatment plants based on anaerobic digestion, supernatant and outflows from sludge dewatering systems contain significantly high amount of ammonium. Generally, these waters are returned to the head of wastewater treatment plant (WWTP), thereby increasing the total nitrogen load of the influent flow. Ammonium from these waters can be recovered and commercially utilised using novel ion-exchange materials. Mackinnon et al. have described an approach for removal and recovery of ammonium from side stream centrate returns obtained from anaerobic digester of a typical WWTP. Most of the ammonium from side streams can potentially be removed, which significantly reduces overall inlet demand at a WWTP. However, the extent of reduction achieved depends on the level of ammonium and flow-rate in the side stream. The exchange efficiency of the ion-exchange material, MesoLite, used in the ammonium recovery process deteriorates with long-term use due to mechanical degradation and use of regenerant. To ensure that a sustainable process is utilised a range of potential applications for this “spent” MesoLite have been evaluated. The primary focus of evaluations has been use of ammonium-loaded MesoLite as a source of nitrogen and growth medium for plants. A MesoLite fertiliser has advantage over soluble fertilisers in that N is held on an insoluble matrix and is gradually released according to exchange equilibria. Many conventional N fertilisers are water-soluble and thus, instantly release all applied N into the soil solution. Loss of nutrient commonly occurs through volatilisation and/or leaching. On average, up to half of the N delivered by a typical soluble fertiliser can be lost through these processes. In this context, use of ammonium-loaded MesoLite as a fertiliser has been evaluated using standard greenhouse and field-based experiments for low fertility soils. Rye grass, a suitable test species for greenhouse trials, was grown in 1kg pots over a period of several weeks with regular irrigation. Nitrogen was applied at a range of rates using a chemical fertiliser as a control and using two MesoLite fertilisers. All other nutrients were applied in adequate amounts. All treatments were replicated three times. Plants were harvested after four weeks, and dry plant mass and N concentrations were determined. At all nitrogen application rates, ammonium-loaded MesoLite produced higher plant mass than plants fertilised by the chemical fertiliser. The lower fertiliser effectiveness of the chemical fertliser is attributed to possible loss of some N through volatilisation. The MesoLite fertilisers did not show any adverse effect on availability of macro and trace nutrients, as shown by lack of deficiency symptoms, dry matter yield and plant analyses. Nitrogen loaded on to MesoLite in the form of exchanged ammonium is readily available to plants while remaining protected from losses via leaching and volatilisation. Spent MesoLite appears to be a suitable and effective fertiliser for a wide range of soils, particularly sandy soils with poor nutrient holding capacity.

Uniform Civil Procedure Rules r150 : orders relating to "property" – whether sperm extracted and stored may be characterised as “property”

In Bazley v Wesley Monash IVF Pty Ltd [2010] QSC 118 an order was made under r 250 of the Uniform Civil Procedure Rules 1999 (Qld) (“UCPR”) requiring the respondent to continue to hold and maintain straws of semen belonging to the applicant’s deceased husband. The decision includes a useful analysis of the development of the common law regarding property rights in human bodies and body parts.

Generating transgenic banana (cv. Sukali Ndizi) resistant to Fusarium Wilt

Banana is one of the world’s most popular fruit crops and Sukali Ndizi is the most popular dessert banana in the East African region. Like other banana cultivars, Sukali Ndizi is threatened by several constraints, of which the Fusarium wilt disease is the most destructive. Fusarium wilt is caused by a soil-borne fungus, Fusarium oxysporum f.sp. cubense (Foc). No effective control strategy currently exists for this disease and although disease resistance exists in some banana cultivars, introducing resistance into commercial cultivars by conventional breeding is difficult because of low fertility. Considering that conventional breeding generates hybrids with additional undesirable traits, transformation is the most suitable way of introducing resistance in the banana genome. The success of this strategy depends on the availability of genes for genetic transformation. Recently, a novel strategy involving the expression of anti-apoptosis genes in plants was shown to result in resistance against several necrotrophic fungi, including Foc race 1 in banana cultivar Lady Finger. This thesis explores the potential of a plant-codon optimised nematode anti-apoptosis gene (Mced9) to provide resistance against Foc race 1 in dessert banana cultivar Sukali Ndizi. Agrobacterium-mediated transformation was used to transform embryogenic cell suspension of Sukali Ndizi with plant expression vector pYC11, harbouring maize ubiquitin promoter driven Mced9 gene and nptII as a plant selection marker. A total of 42 independently transformed lines were regenerated and characterized. The transgenic lines were multiplied, infected and evaluated for resistance to Foc race 1 in a small pot bioassay. The pathogenicity of the Ugandan Foc race 1 isolate used for infection was pre-determined and the spore concentration was standardised for consistent infection and symptom development. This process involved challenging tissue culture plants of Sukali Ndizi, a Foc race 1 susceptible cultivar and Nakinyika, an East African Highland cultivar known to be resistant to Foc race 1, with Fusarium inoculum and observing external and internal disease symptom development. Rhizome discolouration symptoms were the best indicators of Fusarium wilt with yellowing being an early sign of disease. Three transgenic lines were found to show significantly less disease severities compared to the wild-type control plants after 13 weeks of infection, indicating that Mced9 has the potential to provide tolerance to Fusarium wilt in Sukali Ndizi.

Strategies for improved disease resistance in micro-propagated bananas

Bananas (Musa sp) are one of the most important food crops in the world and provide a staple food and source of income in many households especially in Africa. Diseases are a major constraint to production with bunchy top, caused by Banana bunchy top virus (BBTV) generally considered the most important virus disease of bananas worldwide. Of the fungal diseases, Fusarium wilt, caused by the Fusarium oxysporum f.sp cubense (Foc), and black Sigatoka, caused by Mycosphaerella fijiensis, are arguably two of the most important and cause significant yield losses. The low fertility of commercially important banana cultivars has hampered efforts to generate disease resistance using conventional breeding. Possible alternative strategies to generate or increase disease resistance are through genetic engineering or by manipulation of the innate plant defence mechanisms, namely systemic acquired resistance (SAR). The first research component of this thesis describes attempts to generate BBTV-resistant banana plants using a genetic modification approach. The second research component of the thesis focused on the identification of a potential marker gene associated with SAR in banana plants and a comparison of the expression levels of the marker gene in response to biotic and abiotic stresses, and chemical inducers. Previous research at QUT CTCB showed that replication of BBTV DNA components in banana embryogenic cell suspensions (ECS) was abolished following co-bombardment with 1.1mers of mutated BBTV DNA-R. BBTV DNA-R encodes the master replication protein (Rep) and is the only viral protein essential for BBTV replication. In this study, ECS of banana were stably transformed with the same constructs, each containing a different mutation in BBTV DNA-R, namely H41G, Y79F and K187M, to examine the effect on virus replication in stably transformed plants. Cells were also transformed with a construct containing a native BBTV Rep. A total of 16, 16, 11 and five lines of stably transformed banana plants containing the Y79F, H41G, K187M and native Rep constructs, respectively, were generated. Of these, up to nine replicates from Y79F lines, four H41G lines, seven K187M lines and three native Rep lines were inoculated with BBTV by exposure to viruliferous aphids in two separate experiments. At least one replicate from each of the nine Y79F lines developed typical bunchy top symptoms and all tested positive for BBTV using PCR. Of the four H41G lines tested, at least one replicate from three of the lines showed symptoms of bunchy top and tested positive using PCR. However, none of the five replicates of one H41G line (H41G-3) developed symptoms of bunchy top and none of the plants tested positive for BBTV using PCR. Of the seven K187M lines, at least one replicate of all lines except one (K187M-1) developed symptoms of bunchy top and tested positive for BBTV. Importantly, none of the four replicates of line K187M-1 showed symptoms or tested positive for BBTV. At least one replicate from each of the three native Rep lines developed symptoms and tested positive for BBTV. The H41G-3 and K187M-1 lines possibly represent the first transgenic banana plants generated using a mutated Rep strategy. The second research component of this thesis focused on the identification of SAR-associated genes in banana and their expression levels in response to biotic and abiotic stresses and chemical inducers. The impetus for this research was the observation that tissue-cultured (TC) banana plants were more susceptible to Fusarium wilt disease (and possibly bunchy top disease) than plants grown from field-derived suckers, possibly due to decreased levels of SAR gene expression in the former. In this study, the pathogenesis-related protein 1 (PR-1) gene was identified as a potential marker for SAR gene expression in banana. A quantitative real-time PCR assay was developed and optimised in order to determine the expression of PR-1, with polyubiquitin (Ubi-1) found to be the most suitable reference gene to enable relative quantification. The levels of PR-1 expression were subsequently compared in Lady Finger and Cavendish (cv. Williams) banana plants grown under three different environmental conditions, namely in the field, the glass house and in tissue-culture. PR-1 was shown to be expressed in both cultivars growing under different conditions. While PR-1 expression was highest in the field grown bananas and lowest in the TC bananas in Lady Finger cultivar, this was not the case in the Cavendish cultivar with glass house plants exhibiting the lowest PR-1 expression compared with tissue culture and field grown plants. The important outcomes of this work were the establishment of a qPCR-based assay to monitor PR-1 expression levels in banana and a preliminary assessment of the baseline PR-1 expression levels in two banana cultivars under three different growing conditions. After establishing the baseline PR-1 expression levels in Cavendish bananas, a study was done to determine whether PR-1 levels could be increased in these plants by exposure to known banana pathogens and non-pathogens, and a known chemical inducer of SAR. Cavendish banana plants were exposed to pathogenic Foc subtropical race 4 (FocSR4) and non-pathogenic Foc race 1 (Foc1), as well as two putative inducers of resistance, Fusarium lycopersici (Fol) and the chemical, acibenzolar-S-methyl (BION®). Tissue culture bananas were acclimatised under either glass house (TCS) or field (TCH) conditions and treatments were carried out in a randomised complete block design. PR-1 expression was determined using qPCR for both TCS and TCH samples for the period 12-72h post-exposure. Treatment of TCH plants using Foc1 and FocSR4 resulted in 120 and 80 times higher PR-1 expression than baseline levels, respectively. For TCS plants treated with Foc1, PR-1 expression was 30 times higher than baseline levels at 12h post-exposure, while TCS plants treated with FocSR4 showed the highest PR-1 expression (20 times higher than baseline levels) at 72h post-exposure. Interestingly, when TCS plants were treated with Fol there was a marked increase of PR-1 expression at 12 h and 48 h following treatment which was 4 and 8 times higher than the levels observed when TCS plants were treated with Foc1 and FocSR4, respectively. In contrast, when TCH plants were treated with Fol only a slight increase in PR-1 expression was observed at 12 h, which eventually returned to baseline levels. Exposure of both TCS and TCH plants to BION® resulted in no effect on PR-1 expression levels at any time-point. The major outcome of the SAR study was that the glass house acclimatised tissue culture bananas exhibited lower PR-1 gene expression compared to field acclimatised tissue culture plants and the identification of Fol as a good candidate for SAR induction in banana plants exhibiting low PR-1 levels. A number of outcomes that foster understanding of both pathogen-derived and plant innate resistance strategies in order to potentially improve banana resistance to diseases were explored in this study and include identification of potential inducers of systemic acquired resistance and a promising mutated Rep approach for BBTV resistance. The work presented in this thesis is the first report on the generation of potential BBTV resistant bananas using the mutated Rep approach. In addition, this is the first report on the status of SAR in banana grown under different conditions of exposure to the biotic and abiotic environment. Further, a robust qPCR assay for the study of gene expression using banana leaf samples was developed and a potential inducer of SAR in tissue culture bananas identified which could be harnessed to increase resistance in tissue culture bananas.

The bioeconomics of nutritional poverty and child labour

This paper provides a bio-economic foundation of fertility and child labor. Drawing on the clinical and physiological literature, the model highlights the interaction between work efforts of adults and children, their subsistence consumption, and fertility. The subsistence consumption requirements are endogenous to physical efforts. Parents engaged in physically demanding occupations (e.g. non-mechanized agriculture) are likely to suffer from energy deficiency, leading to reduced future work-capacity. Consumption smoothing occurs through bearing a large number of children who provide income support as adults. Although net cost of an additional child is positive, the cost is balanced by the additional income accruing though child employment. In contrast, parents in low-physical effort occupations are less likely to su¤er from nutritional deficiency, and thus tend to have lower fertility and child labor.

Sertoli cells as paracrine modulators of DNA synthesis in rat peritubular myoid cells in culture

To determine whether Sertoli cells influence DNA synthesis by rat peritubular myoid cells in vitro, the effects of Sertoli cells on [3H]thymidine incorporation by peritubular myoid cells in a coculture situation were examined. Incubation of testicular peritubular myoid cells with Sertoli cells in coculture induced a significant increase in [3H]thymidine incorporation by peritubular myoid cells. This indicates a cell-cell cooperation between Sertoli and peritubular myoid cells in the testis in terms of DNA synthesis. Secreted factors from Sertoli cells, as tested in a parabiotic culture situation, also increased [3H]thymidine incorporation by peritubular myoid cells. Moreover, in terms of total cellular protein, cocultures of Sertoli cells and peritubular myoid cells resulted in a significant increase when compared with the monocultures, and this coculture effect substituted for the stimulatory response of serum on peritubular myoid cell monoculture. This study investigated the cooperative role of Sertoli cells and peritubular myoid cells in paracrine regulation of testicular functions.

CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents

Severely reduced fertility is a common finding in cystic fibrosis (CF). We used in situ hybridization to examine the cell-specific expression of CFTR in the reproductive organs of rodents. In males CFTR mRNA is found in the round spermatids (spermatogenic stages V-X) and in the principal cells that line the initial segment of the epididymis. In both the testis and the epididymis, CFTR expression is developmentally regulated suggesting that the defect in the genital tract of male CF patients is of developmental origin. CFTR expression in the luminal and glandular epithelium of the uterus is regulated during the oestrous cycle and is maximal at pro-oestrus. Our results provide a biological rationale for the reduced fertility of CF patients, and suggest a possible cause for the comparatively poorer prognosis for women with CF.