Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates

Abstract

BackgroundSexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates.MethodsWe assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico).ResultsIUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence.ConclusionsIn spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0081-y) contains supplementary material, which is available to authorized users.

A comparative study of litter size and sex composition in a large dataset of callitrichine monkeys

“…We did not detect survival or reproductive costs of being born into a mixed‐sex litter for either males or females (Figure S1). This finding recapitulates a growing literature which espouses that callitrichines, unlike other litter‐bearing mammals (Hackländer & Arnold, ; Korsten, Clutton‐Brock, Pilkington, Pemberton, & Kruuk, ; Monclús & Blumstein, ; Ryan & Vandenbergh, ), have evolved mechanisms which shield females from brother‐derived masculinization (Bradley et al, ; French et al, ). This is true even in wild golden lion tamarins ( L. rosalia ): individuals from mixed‐sex litters were indistinguishable from those from isosexual litters in several morphological (growth to maturity and adult body size), survival (lifetime survivorship), and reproductive metrics (age at first reproduction, reproductive rates, and reproductive tenures; Frye, B.M., Hankerson, Sears, Tardif, & Dietz, n.d.).…”

“…However, in some species (i.e., Callithrix jacchus ), captive mothers routinely produce larger litters because of excess energy stores, which impacts ovulation dynamics (Tardif, Layne, & Smucny, ). The sex composition of litters also may mediate individuals' developmental outcomes—for example, via exposure to sex hormones produced by males—but the overall evidence of such sex‐related effects on development remains mixed (Bradley et al, ; De Moura, ; French et al, ; Frye, Rapaport, Melber, Sears, & Tardif, ; Rutherford, DeMartelly, Layne Colon, Ross, & Tardif, ).…”

Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice

“…In the testis differentiation of Rspo1 / Sox9 -double null XX mice, Sox8 appears to act as a pro-testis gene that induces male differentiation without any actions of SRY and SOX9 [19,41,42]. AMH also acts as a masculinizing factor in the female embryos of several mammals, including those with freemartin syndrome (Bogdanova et al [43]; French et al [44] and references therein). In previous in vivo and in vitro experiments, excessive AMH exposure was able to induce seminiferous cord-like structures in fetal rodent ovaries [45,46].…”