What are the autism research priorities of autistic adults in Scotland?

LAY ABSTRACT: Although research has the potential to improve autistic people's lives, lots of funding goes towards research looking at topics which autistic people say has little impact in their everyday lives. Autistic people's lives can be different depending on where they live, and Scotland is a unique country in many ways. We wanted to find out which topics autistic people in Scotland want to see research on. Our team of autistic and non-autistic researchers (including university-based and community researchers) created a survey where 225 autistic adults rated and ranked the importance of possible research topics and shared their thoughts on what topics mattered to them. The five most important topics were mental health and well-being, identifying and diagnosing autistic people, support services (including healthcare and social care), non-autistic people's knowledge and attitudes and issues impacting autistic women. The three least important topics were genetics or biological aspects of autism, autism treatments/interventions and causes of autism. Our findings indicate that autistic people in Scotland want research to focus on things that matter to their day-to-day lives. Also, the Scottish government says they will be listening to autistic people in their latest policy plans, and we believe that considering autistic people's research priorities is an important part of this. Our findings also add to growing calls for change to happen in how and what autism researchers do research on.

Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep.

In the agonadal, androgenized ewe testosterone before birth produces a precocious pubertal rise in circulating LH and abolishes the LH surge mechanism. The present study tested two predictions from this model in the ovary-intact female: 1) prenatal androgen exposure produces early ovarian stimulation; and 2) despite early ovarian stimulation, progestogenic cycles would not occur because of the abolition or disruption of the LH surge. Pregnant ewes were injected with testosterone propionate twice per week from either d 30-90 (T60 group; 100 mg/injection) or d 60-90 (T30 group; 80 mg/injection) of gestation (term, 147 d). Control ewes received no injections. At birth, the androgenized and control lambs were divided into two groups: ovary-intact to determine the effects of prenatal androgen on the timing of puberty and subsequent ovarian function, and ovariectomized to assess the timing of the pubertal decrease in sensitivity to estrogen negative feedback and the subsequent increase in LH. Neonatally orchidectomized, estrogen-treated males were included for comparison of the timing of this pubertal rise in LH secretion. Neuroendocrine puberty (determined on the basis of LH increase) was advanced in the androgenized females to a similar age as in males. Repeated progesterone cycles of the same duration and number occurred in the ovary-intact ewes, and they began at the same time as for control females, thus negating both predictions. Differences appeared during the second breeding season, when reproductive cycles were either absent (T60) or disrupted (T30 group). Our findings reveal that exposure to androgens in utero causes a progressive loss of cyclic function in adulthood.

In utero programming of sexually differentiated gonadotrophin releasing hormone (GnRH) secretion.

It has long been recognised that steroids can have both organisational and activational effects on the reproductive neuroendocrine axis of many species, including the sheep. Specifically, if the ovine foetus is exposed to testosterone during a relatively short 'window' of in utero development (from approximately day 30-90 of a 147 day pregnancy) the neural mechanisms regulating gonadotrophin releasing hormone (GnRH) secretion become organised in a male-specific manner. In post-natal life the consequences of foetal androgen exposure are sexually differentiated responses of the GnRH neuronal network to activation by factors such as photoperiod and ovarian steroid hormones. Studies in the gonadectomized lamb have demonstrated that elevated concentrations of oestrogen (E) are unable to trigger a preovulatory-like GnRH surge in the male and the androgenized ewe lamb. Further, these animals have markedly reduced sensitivity to the inhibitory actions of progesterone on tonic GnRH release compared with normal ewes. The reasons for these abnormal steroid feedback mechanisms may reside in sexually dimorphic inputs to the GnRH neurone, including those from oestrogen-receptive neurones in the arcuate nucleus that synthetize the neuropeptide, neurokinin B (NKB). The consequences of in utero androgen exposure are reflected in a progressive and dramatic impairment of fertility in the ovary-intact ewe.

Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep.

We studied the impact of prenatal androgen exposure on the timing of onset of puberty, maintenance of cyclicity in the first breeding season, and the LH surge mechanism in female sheep. Pregnant sheep were injected with testosterone propionate (100 mg i.m.) twice each week from Day 30 to Day 90 (D30-90) or from Day 60 to Day 90 (D60-90) of gestation (term = 147 days). Concentrations of plasma progesterone and gonadotropins were measured in blood samples collected twice each week from control (n = 10), D60-90 (n = 13), and D30-90 (n = 3) animals. Rate of weight gain and initiation of estrous behavior were also monitored. After the first breeding season, when the animals entered anestrus, competency of the gonadotropin surge system to respond to estradiol positive feedback was tested in the absence or presence of progesterone priming for 12 days. Prenatally androgenized females had similar body weight gain and achieved puberty (start of first progestogenic cycle) at the same time as controls. Duration of the breeding season and the number of cycles that occurred during the first breeding season were similar between control and prenatally androgenized sheep. In contrast, prenatal exposure to androgens compromised the positive feedback effects of estradiol. Onset of LH/FSH surges following the estradiol stimulus was delayed in both groups of androgenized ewes compared with the controls in both the absence and presence of progesterone priming. In addition, the magnitude of LH and FSH surges in the two animals that surged in the D30-90 group were only one third and one half, respectively, of the magnitudes observed in the control and D60-90 groups. The present findings indicate that disruption of the surge system can account for the fertility problems that occur during adulthood in prenatally androgenized sheep.

Prenatal exposure of the ovine fetus to androgens sexually differentiates the steroid feedback mechanisms that control gonadotropin releasing hormone secretion and disrupts ovarian cycles.

Exposure of the female sheep fetus to exogenous testosterone in early pregnancy permanently masculinizes the reproductive neuroendocrine axis. Specifically, in utero androgens given to female lambs from day 30 to 90 of a 147 day pregnancy dramatically altered the response of the gonadotropin releasing hormone (GnRH) neuronal network in the hypothalamus to both estrogen (E) and progesterone (P) feedback. Elevated concentrations of estrogen stimulated a massive release of GnRH in gonadectomized female sheep; however, male and androgenized female lambs were unable to respond to high E concentrations by producing this preovulatory-like "surge" of GnRH. Further, the inhibitory actions of progesterone (P) were also sexually differentiated and adult males and androgenized females were much less responsive to P-negative feedback than normal ewes. The consequences of these abnormal steroid feedback mechanisms were reflected in the fact that only 72% of ovary-intact androgenized ewes exhibited normal estrous cycles in their first breeding season whereas none had a single estrous cycle during the second breeding season. In contrast, 100% of the control animals exhibited repeated reproductive cycles in both seasons. These data indicate that a relatively short exposure to male hormones during in utero life permanently alters the neural mechanisms that control reproduction and leads progressively to a state of infertility.