key: cord-0271408-6nss5gc0
authors: van Rosmalen, Laura; van Dalum, Jayme; Hazlerigg, David G.; Hut, Roelof A.
title: Gonads or body? Differences in gonadal and somatic photoperiodic growth response in two vole species
date: 2020-06-12
journal: bioRxiv
DOI: 10.1101/2020.06.12.147777
sha: a45e6679b65d08bf8381652b65cbae55786e54ad
doc_id: 271408
cord_uid: 6nss5gc0

To optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a higher critical photoperiod for reproductive onset is necessary in northern species to arrest reproductive development until spring onset. Temperature-photoperiod relationships, and hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated photoperiodic responses at different times during development in northern- (tundra/root vole, Microtus oeconomus) and southern vole species (common vole, Microtus arvalis) exposed to constant short (SP) or long photoperiod (LP). M. oeconomus grows faster under LP, whereas no photoperiodic effect on somatic growth is observed in M. arvalis. Contrastingly, gonadal growth is more sensitive to photoperiod in M. arvalis, suggesting that photoperiodic responses in somatic and gonadal growth can be plastic, and might be regulated through different mechanisms. In both species, thyroid-stimulating-hormone-β subunit (Tshβ) and iodothyronine-deiodinase 2 (Dio2) expression is highly increased under LP, whereas Tshr and Dio3 decreases under LP. High Tshr levels in voles raised under SP may lead to increased sensitivity to increasing photoperiods later in life. The higher photoperiodic induced Tshr response in M. oeconomus suggests that the northern vole species might be more sensitive to TSH when raised under SP. Species differences in developmental programming of the PNES, which is dependent on photoperiod early in development, may form part divergent breeding strategies evolving as part of latitudinal adaptation. Summary statement Development of the neuroendocrine system driving photoperiodic responses in gonadal and somatic growth differ between the common and the tundra vole, indicating that they use a different breeding strategy.

Organisms use intrinsic annual timing mechanisms to adaptively prepare behavior, 92 physiology, and morphology for the upcoming season. In temperate regions, decreased 93 ambient temperature is associated with reduced food availability during winter which will 94 impose increased energetic challenges that completely prevent the possibility of successfully 95 raising offspring. Annual variation in ambient temperature shows large fluctuations between 96 years, with considerable day to day variations, whereas annual changes in photoperiod 97 provide a consistent year-on-year signal for annual phase. This has led to convergent 98 evolutionary processes in many organisms to use day length as the most reliable cue for 99 seasonal adaptations. 100

In mammals, the Williams and Morgan, 1988). Under long days, pineal melatonin is released for a short 108 duration and thyroid stimulating hormone  subunit (Tsh) expression is increased in the pars 109 tuberalis, leading to increased secretion of TSH. PT-derived TSH acts locally through TSH 110 receptors (TSHr) found in the tanycytes in the neighbouring mediobasal hypothalamus 111 (MBH). The tanycytes produce increased iodothyronine deiodinase 2 (DIO2) and decreased 112 DIO3 levels, which leads to higher levels of the active form of thyroid hormone (T3) and 113 lower levels of inactive forms of thyroid hormone (T4 and rT3). In small mammals, it is 114 likely that T3 acts 'indirectly', through KNDy (kisspeptin/neurokininB/Dynorphin) neurons of 115 the arcuate nucleus (ARC) (for review see Simonneaux, 2020) in turn controlling the activity 116 of gonadotropin-releasing hormone (GnRH) neurons. GnRH neurons project to the pituitary 117 to induce gonadotropin release, which stimulates gonadal growth. The neuroanatomy of this 118 mechanism has been mapped in detail and genes and promoter elements that play a crucial 119 role in this response pathway have been identified in several mammalian species ( Yellon and Goldman, 1984) . Maternal photoperiodic information is transferred to the young 133 in utero by melatonin in several rodent species (Horton and Stetson, 1992; Yellon and Longo, 134 1987) . By passing information about day length from mother to fetus, offspring will be 135 prepared for the upcoming season. Presumably, crucial photoperiod-dependent steps in PNES 136 development take place in young animals to secure an appropriate seasonal response later in 

Photoperiod during gestation did not affect birth weight in either species ( Fig. 2A,B) . Both 248 M. oeconomus males and females grow faster under LP compared to SP conditions (males, 249 F1,303 = 15.0, p < 0.001; females, F1,307 = 10.2, p < 0.01) ( Fig. 2A,B) . However, no effect of 250 photoperiod on body mass was observed in M. arvalis males or females (males, F1,243 = 2.1, 251 ns; females, F1,234 = 0.6, ns) ( Fig. 2A,B) (Fig. 2C,E) . This photoperiodic effect on testis 256 development is less pronounced in M. oeconomus (testis, F1,35 = 8.3, p < 0.01; GSI, F1,35 = 257 9.3, p < 0.01) (Fig. 2C,E) . 258

M. arvalis female gonadal weight (i.e. paired ovary + uterus) is slightly higher in the 260 beginning of development (until 30 days old) under SP compared to LP conditions (F1,17 = 10.4, p < 0.01) (Fig. 2D) , while the opposite effect was observed in M. oeconomus (F1,36 = 262 9.0, p < 0.01) (Fig. 2D) . For both species, these photoperiodic effects disappeared when 263 gonadal mass was corrected for body mass (M. arvalis, F1,17 = 2.5, ns; M. oeconomus, F1,36 = 264 2.3, ns) (Fig. 2F) . Interestingly, gonadal weight is significantly increasing in 30-50 days old 265 LP M. arvalis females (F1,5 = 7.7, p < 0.05) (Fig. 2D) 

In males of both species, Mtnr1a expression in the hypothalamic block with preserved pars 280 tuberalis was highly expressed, but unaffected by photoperiod or age (photoperiod, F1,43 = 281 0.08, ns; age, F3,42 = 0.94, ns) (Fig. 3A) . In females, Mtnr1a expression increases 282 approximately 2-fold with age in both species (F3,40 = 9.04, p < 0.001) (Fig. 3B) (Fig. 3E,F) . 296

Photoperiodic responses on Tshr expression are significantly larger in M. oeconomus males 297 compared to M. arvalis males (F1,42 = 8.17, p < 0.01) (Fig. 3E) . 298

In males of both species, the largest photoperiodic effect on Dio2 is found at weaning 299 (day 21), with higher levels under LP compared to SP (F1,42 = 14.7, p < 0.001) (Fig. 3G) . 300

Interestingly, Dio3 is lower in these animals (F1,42 = 4.8, p < 0.05) (Fig. 3I ), leading to a high 301 Dio2/Dio3 ratio under LP in the beginning of development (F1,42 = 8.5, p < 0.01) (Fig. 3K) . 302

We find a similar pattern in females, with higher Dio2 under LP compared to SP at the 303 beginning of development (i.e. day 15) (F3,10 = 8.9, p < 0.01) (Fig. 3H) . is higher under LP dependent on age (F3,40 = 3.51, p < 0.05) (Fig. S1D,F) , but there were no effects of photoperiod on Eya3 (F1,40 = 0.30, ns), Dntm1 (F1,40 = 0.18, ns) and Dnmt3a (F1,40 310 = 0.08, ns) (Fig. S1B,H,J) . (Fig. 4A-D) . Moreover, no significant 357 relationship between Dio2 and Dio3 expression was found (Fig. 4E-H) . 

These data demonstrate that photoperiod early in life affects pup growth in M. oeconomus 374 ( Fig. 2A) , and reproductive development in M. arvalis males (Fig. 2C,E) . In females, a 375 similar photoperiodic effect on somatic growth is observed as in males. M. oeconomus 376 females grow faster under LP compared to SP, while there is no difference in growth rates 377 between LP and SP in M. arvalis (Fig. 2B) in LP animals, whereas gonadal weight in SP females remains the same (Fig. 2D,F) In females, both Kiss1 and Npvf expression is higher under LP dependent on age (Fig.  507 S1D,F), whereas in males no effects of photoperiod on these genes are found (Fig. S1C,E) . 508

Other studies report inconsistent photoperiodic/seasonal effects on ARC Kiss1 expression in 509 different species, which may be related to a negative sex steroid feedback on 

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